International Natural Procreative Technology Evaluation and Surveillance of Treatment for Subfertility (iNEST): enrollment and methods

Stanford JB, Parnell T, Kantor K, Reeder MR, Najmabadi S, Johnson K, Musso I, Hartman H, Tham E, Winter I, Galczynski K, Carus A, Sherlock A, Golden Tevald J, Barczentewicz M, Meier B, Carpentier PA, Poehailos K, Chasuk R, Lipscomb L, Danis PG

Abstract:
STUDY QUESTION: What is the feasibility of a prospective protocol to follow subfertile couples being treated with natural procreative technology for up to 3 years at multiple clinical sites?

SUMMARY ANSWER: Overall, clinical sites had missing data for about one-third of participants, the proportion of participants responding to follow-up questionnaires during time periods when participant compensation was available (about two-thirds) was double that of time periods when participant compensation was not available (about one-third) and follow-up information was most complete for pregnancies and births (obtained from both clinics and participants).

WHAT IS KNOWN ALREADY: Several retrospective single-clinic studies from Canada, Ireland and the USA, with subfertile couples receiving restorative reproductive medicine, mostly natural procreative technology, have reported adjusted cumulative live birth rates ranging from 29% to 66%, for treatment for up to 2 years, with a mean women's age of about 35 years.

STUDY DESIGN SIZE DURATION: The international Natural Procreative Technology Evaluation and Surveillance of Treatment for Subfertility (iNEST) was designed as a multicenter, prospective cohort study, to enroll subfertile couples seeking treatment for live birth, assess baseline characteristics and follow them up for up to 3 years to report diagnoses, treatments and outcomes of pregnancy and live birth. In addition to obtaining data from medical record abstraction, we sent follow-up questionnaires to participants (both women and men) to obtain information about treatments and pregnancy outcomes, including whether they obtained treatment elsewhere. The study was conducted from 2006 to 2016, with a total of 10 clinics participating for at least some of the study period across four countries (Canada, Poland, UK and USA).

PARTICIPANTS/MATERIALS SETTING

METHODS: The 834 participants were subfertile couples with the woman's age 18 years or more, not pregnant and seeking a live birth, with at least one clinic visit. Couples with known absolute infertility were excluded (i.e. bilateral tubal blockage, azoospermia). Most women were trained to use a standardized protocol for daily vulvar observation, description and recording of cervical mucus and vaginal bleeding (the Creighton Model FertilityCare System). Couples received medical and sometimes surgical evaluation and treatments aimed to restore and optimize female and male reproductive function, to facilitate in vivo conception.

MAIN RESULTS AND THE ROLE OF CHANCE: The mean age of women starting treatment was 34.0 years; among those with additional demographic data, 382/478 (80%) had 16 or more years of education, and 199/659 (30%) had a prior live birth. Across 10 clinical sites in four countries (mostly private clinical practices) with family physicians or obstetrician-gynecologists, data about clinic visits were submitted for 60% of participants, and diagnostic data for 77%. For data obtained directly from the couple, 59% of couples had at least one follow-up questionnaire, and the proportion of women and men responding to fill out the follow-up questionnaires was 69% and 67%, respectively, when participant financial compensation was available, compared to 38% and 33% when compensation was not available. Among all couples, 57% had at least one pregnancy and 44% at least one live birth during the follow-up time period, based on data obtained from clinic and/or participant questionnaires. All sites reported on female pelvic surgical procedures, and among all participants, 22% of females underwent a pelvic diagnostic and/or therapeutic procedure, predominantly laparoscopy and hysterosalpingography. Among the 643 (77%) of participants with diagnostic information, ovulation-related disorders were diagnosed in 87%, endometriosis in 31%, nutritional disorders in 47% and abnormalities of semen analysis in 24%. The mean number of diagnoses per couple was 4.7.

LIMITATIONS REASONS FOR CAUTION: The level of missing data was higher than anticipated, which limits both generalizability and the ability to study different components of treatment and prognosis. Loss to follow-up may also be differential and introduce bias for outcomes. Most of the participating clinicians were not surgeons, which limits the opportunity to study the impact of surgical interventions. Participants were geographically dispersed but relatively homogeneous with regard to socioeconomic status, which may limit the generalizability of current and future findings.

WIDER IMPLICATIONS OF THE FINDINGS: Multicenter studies are key to understanding the outcomes of subfertility treatments beyond IVF or IUI in broader populations, and the association of different prognostic factors with outcomes. We anticipate that the iNEST study will provide insight for clinical and treatment factors associated with outcomes of pregnancy and live birth, with appropriate attention to potential biases (including adjustment for potential confounders, multiple imputation for missing data, sensitivity analysis and inverse probability weighting for potential differential loss to follow-up, and assessments for clinical site heterogeneity). Future studies will need to either have: adequate funding to compensate clinics and participants for robust data collection, including targeted randomized trials; or a scaled-down, registry-based approach with targeted data points, similar to the multiple national and regional ART registries.

STUDY FUNDING/COMPETING INTERESTS: Funding for the study came from the International Institute for Restorative Reproductive Medicine, the University of Utah, Department of Family and Preventive Medicine, Health Studies Fund, the Primary Children's Medical Foundation, the Mary Cross Tippmann Foundation, the Atlas Foundation, the St. Augustine Foundation and the Women's Reproductive Health Foundation. The authors declare no competing interests.

TRIAL REGISTRATION NUMBER: The iNEST study is registered at clinicaltrials.gov, NCT01363596.


Prospectively assessed perceived stress associated with early pregnancy losses  among women with history of pregnancy loss

Stefanie N Hinkle

Abstract:
STUDY Question: What is the association between perceived stress during peri-conception and early pregnancy and pregnancy loss among women who have experienced a prior pregnancy loss?

SUMMARY ANSWER: Daily perceived stress above the median is associated with over a 2-fold risk of early pregnancy loss among women who have experienced a prior loss. WHAT IS KNOWN ALREADY? Women who have experienced a pregnancy loss may be more vulnerable to stress while trying to become pregnant again. While prior research has indicated a link between psychological stress and clinically confirmed miscarriages, research is lacking among a pre-conceptional cohort followed prospectively for the effects of perceived stress during early critical windows of pregnancy establishment on risk of both hCG-detected pregnancy losses and confirmed losses, while considering important time-varying confounders.

STUDY DESIGN, SIZE, DURATION: Secondary data analysis of the EAGeR trial (2007-2011) among women with an hCG-detected pregnancy (n = 797 women).

PARTICIPANTS/MATERIALS, SETTING, Methods: Women from four US clinical centers enrolled pre-conceptionally and were followed ≤6 cycles while attempting pregnancy and, as applicable, throughout pregnancy. Perceived stress was captured via daily diaries and end-of-month questionnaires. Main outcome measures include hCG-detected and clinically recognized pregnancy losses.

MAIN RESULTS AND THE ROLE OF CHANCE: Among women who had an hCG-confirmed pregnancy, 188 pregnancies (23.6%) ended in loss. Women with high (>50th percentile) versus low (≤50th percentile) peri-implantation or early pregnancy weekly perceived stress had an elevated risk of experiencing any pregnancy loss (hazard ratio (HR): 1.69, 95% CI: 1.13, 2.54) or clinical loss (HR: 1.58, 95% CI: 0.96, 2.60), with higher risks observed for women experiencing an hCG-detected loss (HR: 2.16, 95% CI: 1.04, 4.46). Models accounted for women's age, BMI, employment, marital status, income, education, race, parity, prior losses, exercise and time-varying nausea/vomiting, caffeine, alcohol and smoking.

LIMITATIONS, REASONS FOR CAUTION: We were limited in our ability to clearly identify the mechanisms of stress on pregnancy loss due to our sole reliance on self-reported perceived stress, and the lack of biomarkers of different pathways of stress.

WIDER IMPLICATIONS OF THE Findings: This study provides new insight on early pregnancy perceived stress and risk of pregnancy loss, most notably hCG-detected losses, among women with a history of a prior loss. Our study is an improvement over past studies in its ability to account for time-varying early pregnancy symptoms, such as nausea/vomiting, and lifestyle factors, such as caffeine, alcohol and smoking, which are also risk factors for psychological stress and pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Additionally, K.C.S. was supported by the National Institute on Aging of the National Institutes of Health under Award Number K01AG058781. The authors have no conflicts of interest to disclose.

TRIAL REGISTRATION NUMBER: #NCT00467363.


Spotlight on the Gut Microbiome in Menopause: Current Insights

Abstract: The gut microbiome is an important contributor to human health, shaped by many endogenous and exogenous factors. The gut microbiome displays sexual dimorphism, suggesting influence of sex hormones, and also has been shown to change with aging. Yet, little is known regarding the influence of menopause - a pivotal event of reproductive aging in women - on the gut microbiome. Here, we summarize what is known regarding the interrelationships of female sex hormones and the gut microbiome, and review the available literature on menopause, female sex hormones, and the gut microbiome in humans. Taken together, research suggests that menopause is associated with lower gut microbiome diversity and a shift toward greater similarity to the male gut microbiome, however more research is needed in large study populations to identify replicable patterns in taxa impacted by menopause. Many gaps in knowledge remain, including the role the gut microbiome may play in menopause-related disease risks, and whether menopausal hormone therapy modifies menopause-related change in the gut microbiome. Given the modifiable nature of the gut microbiome, better understanding of its role in menopause-related health will be critical to identify novel opportunities for improvement of peri- and post-menopausal health and well-being.


Risk factors for anxiety and depression among pregnant women during the COVID-19  pandemic: Results of a web-based multinational cross-sectional study

Kajdy A, Sys D, Pokropek A, Shaw SW, Chang TY, Calda P, Acharya G, Ben-Zion M, Biron-Shental T, Borowski D, Czuba B, Etchegaray A, Feduniw S, Garcia-Mandujano R, Santacruz MG, Gil MM, Hassan S, Kwiatkowski S, Martin-Arias A, Martinez-Portilla RJ, Prefumo F, Rabijewski M, Salomon LJ, Tiller H, Verlohren S, Voon HY, Yanque-Robles OF, Yong SL, Poon LC

Abstract:
Objective: To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies.

Methods: A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULT: Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P < 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances.

Conclusions: According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status.

International Journal of Gynaecology and Obstetrics: the Official Organ of the  International Federation of Gynaecology and Obstetrics


Hormonal contraception and risk of breast cancer and breast cancer in situ among  Swedish women 15-34 years of age: A nationwide register-based study

Kristina Gemzell-Danielsson

Department of Women's and Children's Health, Karolinska institutet, SE-17177 Stockholm, Sweden.

Inger Sundström-Poromaa

Department of Women's and Children's Health, Uppsala university, SE-75185 Uppsala, Sweden.

Abstract:
Background: Evidence on a possible association between newer hormonal contraceptives (HC) and risk of breast cancer remains inconclusive, especially as concerns progestogen-only methods.

Methods: In this nationwide prospective cohort study, all Swedish women aged 15-34 at study start on January 1(st) 2005, or who turned 15 years during the study period, were followed until December 31(st) 2017. Using information from seven National Registers, we assessed the risk ratio of developing breast cancer and breast cancer in situ in relation to different HC using Poisson regression. We adjusted the analyses for several known confounders of breast cancer.

Findings: This cohort included 1.5 million women providing more than 14 million person-years. During the study period, 3842 women were diagnosed with breast cancer. Compared with never users of any HC, we found no increased risk of developing breast cancer among current users of any combined HC, IRR 1.03 (0.91-1.16), whereas current users of progestogen-only methods had an increased risk of developing breast cancer, IRR 1.32 (1.20-1.45). Across all types of HC, the risk of developing breast cancer appeared to be highest the first five years of use (combined HC IRR 1.39 (1.14-1.69); progestogen-only methods IRR 1.74 (1.44-2.10). The risk disappeared ten years after the women stopped using HC. The absolute risk of breast cancer per 100,000 women-years was 22.4 for never users, 10.9 for current users of combined HC, and 29.8 for current users of progestogen-only methods.

Interpretation: Current use of progestogen-only methods is associated with a small increased risk of developing breast cancer, whereas we could only detect an increased risk among users of combined HC during the first five years of use. This may partly be explained by a selective prescription of progestogen-only methods to women with risk factors for breast cancer, like smoking or obesity. As the absolute risk of breast cancer was small, the many health benefits associated with HC must also be taken into account in contraceptive counselling.

Funding: This study was funded by the Swedish Cancer Society and by the Uppsala County Council, the Faculty of Medicine at Uppsala University.


Pooled efficacy results of estetrol/drospirenone combined oral contraception  phase 3 trials

Л. В. Сутурина

Scientific Center of Family Health Problems and Human Reproduction

И.А. Аполихина

National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Healthcare of the Russian Federation

Céline Bouchard

Clinique de Recherche en Santé de la femme (RSF) Inc., Québec City, Québec, Canada.

Inna Apolikhina

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russia.

Larisa Suturina

Department of Reproductive Health Protection, Scientific Center for Family Health and Human Reproduction, Irkutsk, Russia.

János Zatik

Szent Anna Szuleszeti, Nogyogyaszati es Ultrahang Maganrendelo, Debrecen, Hungary.

Abstract:
Objective: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen.

Study Design: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors.

Results: Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m(2). The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI <25 kg/m(2), 25 to 29.9 kg/m(2), and ≥30 kg/m(2) of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance <99% of expected pills (HR 4.21[2.04-8.66]) with conception.

Conclusion: E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable. IMPLICATIONS STATEMENT: Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure.


Relative energy deficiency in sport (RED - S)

Abstract: Relative Energy Deficiency in Sport (RED-S) refers to a condition in which energy imbalance leads to impaired physiological function of multiple organ systems and expands on the diagnosis previously known as the Female Athlete Triad. Researchers attribute the medical complications of RED-S to low energy availability, in which energy availability is defined as dietary energy intake minus exercise energy expenditure divided by fat-free mass. This article reviews the history of this diagnosis, the changing terminology, and the reasons for the expansion. Accepted definitions of each part of the energy availability equation are considered and the difficulties that exist using these equations in practice or comparatively in the literature are assessed. The review analyzes the broad spectrum of health consequences of RED-S, especially as it relates to hypoestrogenemia and menstrual function, gives guidance to those caring for athletes on the identification and management of RED-S, and sheds lights on the important role of coaches, athletic trainers, and families in recognizing this diagnosis and in helping getting patients to care.

Current problems in pediatric and adolescent health care


Polycystic ovary syndrome and postpartum depression among Hispanics and non-Hispanics: a population-based study

Abstract:
Background: Women with polycystic ovary syndrome experience increased health complications during and after pregnancy, including a higher prevalence of postpartum depression. Although previous research has found that Hispanic women with polycystic ovary syndrome experience heightened hyperandrogenism and metabolic effects compared with non-Hispanic women, it is unknown whether they experience other polycystic ovary syndrome-related comorbidities, such as postpartum depression, to a greater degree than their non-Hispanic counterparts.

Objective: This study aimed to determine the associations among a self-reported prepregnancy diagnosis of polycystic ovary syndrome, polycystic ovary syndrome symptoms (irregular menstruation, hirsutism, and acne), and postpartum depression among a national sample of at-risk women and evaluated the potential effect modification by Hispanic ethnicity.

Study Design: The study population included 52,267 postpartum (2-6 months) women who completed the US Pregnancy Risk Assessment Monitoring System Phase 8 questionnaire (2016-2018). Data from US states that captured self-reported polycystic ovary syndrome symptoms in the 3 months before pregnancy (n=17 states) were used. Moreover, we performed a subanalysis restricted to data from the Utah Pregnancy Risk Assessment Monitoring System Phase 8 questionnaire (2016-2019; n=5814), as it was the only state that considered self-reported polycystic ovary syndrome symptoms during this period. Postpartum depressed mood and anhedonia, the postpartum depression outcome measurements, were assessed via the following questions, respectively: (1) "Since your new baby was born, how often have you felt down, depressed, or hopeless?" and (2) "Since your new baby was born, how often have you had little interest or little pleasure in doing things you usually enjoyed?" In addition, postpartum depressed mood and anhedonia were assessed separately and as a combined variable. Here, weighted adjusted prevalence ratios and 95% confidence intervals were used to assess the association between polycystic ovary syndrome and postpartum depressed mood and anhedonia among Hispanic women and non-Hispanic women while taking into account preconception sociodemographics, lifestyle, and health history confounding factors.

Results: The national study population was composed of 16.8% of Hispanic ethnicity, with 11.4% Hispanic women and 17.1% non-Hispanic women reporting prepregnancy polycystic ovary syndrome symptoms. The study found no association between women reporting prepregnancy polycystic ovary syndrome vs women without polycystic ovary syndrome and the prevalence of postpartum depressed mood and/or anhedonia. Moreover, the results were null when we stratified by Hispanic ethnicity. The Utah study population was composed of 15.5% of women of Hispanic ethnicity, with 5.8% of Hispanic women and 7.4% of non-Hispanic women reporting prepregnancy polycystic ovary syndrome. Symptom-based polycystic ovary syndrome (having irregular menstruation with hirsutism or irregular menstruation with acne), compared with having regular menstruation in the Utah sample, was associated with a 1.54 higher adjusted prevalence ratio (95% confidence interval, 1.14-2.09) for postpartum depressed mood and anhedonia. Stratified analyses by ethnicity indicated a 2to 5-fold higher prevalence of postpartum depression with symptom-based polycystic ovary syndrome for Hispanic women and a 1.5-fold higher prevalence for non-Hispanic women.

Conclusion: In this US population-based study, a self-reported prepregnancy diagnosis of polycystic ovary syndrome was not associated with postpartum depression. However, self-reported polycystic ovary syndrome symptoms, including irregular menstruation and acne and/or hirsutism, were associated with a higher probability of postpartum depression, most prominently for Hispanic women. Our findings suggested that capturing polycystic ovary syndrome symptoms among at-risk women may be important for identifying associations with postpartum depression and potentially other comorbidities.


Menstruation and menopause in autistic adults: Periods of importance?

Abstract: Autism spectrum conditions were once seen as a predominantly male condition, but this has caused research to have little focus on women. Therefore, little is known about menstruation and menopause in autism spectrum conditions. Some smaller studies indicate that autistic individuals might suffer from increased difficulties surrounding these events. This study aimed to investigate whether autistic women experience more frequent premenstrual dysphoric disorder, causing extreme physical, emotional, and functional impairment. In a partly overlapping sample, we also examined whether women with autism spectrum condition experience increased complaints surrounding menopause. We did not find an increased prevalence of premenstrual dysphoric disorder in autism spectrum conditions (14.3%) compared with non-autistic women (9.5%). Those with autism spectrum conditions did experience increased menopausal complaints. These menopausal complaints were associated with higher levels of depression and autistic traits. In non-autistic women, menopausal complaints were associated with increased inattention, hyperactivity/impulsivity (i.e. attention deficit hyperactivity disorder traits), and depression. With this work, we show the important role that major reproductive milestones can have in an autistic woman's life.

Autism : the international journal of research and practice


The 13.5-mg, 19.5-mg, and 52-mg Levonorgestrel-Releasing Intrauterine Systems and Risk of Ectopic Pregnancy

Abstract:
OBJECTIVE: To assess the Pearl Index for risk of ectopic pregnancy in women using levonorgestrel-releasing intrauterine systems (LNG-IUS) with hormonal reservoirs of 13.5 mg, 19.5 mg, or 52 mg.

METHODS: This was a retrospective cohort study. Women diagnosed with an ectopic pregnancy in Stockholm County, Sweden, between January 1, 2014, and December 31, 2019, were identified through the electronic medical record system. The final analysis included 2,252 cases of ectopic pregnancy. Information on age, reproductive and medical history, as well as current use of contraception was retrieved. The time of intrauterine device (IUD) insertion before ectopic pregnancy and the numbers of sold LNG-IUS during the study period were used to calculate the incidence rate for ectopic pregnancy during use per 100 woman-years (Pearl Index).

RESULTS: Among women with an ectopic pregnancy diagnosis, 105 presented with a known type of hormonal IUD in situ, of whom 94 were included in the calculations of the Pearl Index. The estimated Pearl Index for ectopic pregnancy was 0.136 (95% CI 0.106-0.176) for the LNG-IUS 13.5-mg, 0.037 (95% CI 0.021-0.067) for the LNG-IUS 19.5-mg, and 0.009 (95% CI 0.006-0.014) for the LNG-IUS 52-mg. With the 52-mg LNG-IUS as referent, the relative risk (RR) for ectopic pregnancy was higher during the first year for LNG 13.5-mg (RR 20.59, 95% CI 12.04-35.21), and for both 13.5-mg (RR 14.49, 95% CI 9.01-23.3) and 19.5-mg (RR 4.44, 95% CI 1.64-12.00) during the total study period.

CONCLUSION: The absolute risk of ectopic pregnancy during the use of LNG-IUS at any doses was low. The results show that the lower the dose of the IUD, the higher the risk of an ectopic pregnancy. Higher-dose LNG-IUS should be considered when providing contraceptive counseling to a woman with known risk factors for ectopic pregnancy who are considering a hormonal IUD.


Health risk assessment of polychlorinated biphenyls (PCBs) in baby clothes. A preliminary study

Abstract: Clothes may contain a large range of chemical additives and other toxic substances, which may eventually pose a significant risk to human health. Since they are associated with pigments, polychlorinated biphenyls (PCBs) may be especially relevant. On the other hand, infants are very sensitive to chemical exposure and they may wear some contact and colored textiles for a prolonged time. Consequently, a specific human health risk assessment is required. This preliminary study was aimed at analyzing the concentrations of PCBs in ten bodysuits purchased in on-line stores and local retailers. The concentrations of 12 dioxin-like and 8 non-dioxin-like PCB congeners were determined by gas chromatography coupled to high resolution mass spectrometry, with detection limits ranging between 0.01 and 0.13 pg/g. The dermal absorption to PCBs of children at different ages (6 months, 1 year and 3 years old) was estimated, and the non-cancer and cancer risks were evaluated. Total levels of PCBs ranged from 74.2 to 412 pg/g, with a mean TEQ concentration of 13.4 pg WHO-TEQ/kg. Bodysuits made of organic cotton presented a total mean PCB concentration substantially lower than clothes made of regular cotton (11.0 vs. 15.8 pg WHO-TEQ/kg). The dermal absorption to PCBs for infants was calculated in around 3·10-5 pg WHO-TEQ/kg·day, regardless the age. This value is > 10,000-fold lower than the dietary intake of PCBs, either through breastfeeding or food consumption. Furthermore, this exposure value would not pose any health risks for the infants wearing those bodysuits. Anyhow, as it is a very preliminary study, this should be confirmed by analyzing larger sets of textile samples. Further investigations should be also focused on the co-occurrence of PCBs and other toxic chemicals (i.e., formaldehyde, bisphenols and aromatic amines) in infant clothes.


Women’s Menstrual Cycles and Ovulation Provide Balanced Estradiol and Progesterone for Fertility and Lifelong Health

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Periodic vaginal bleeding occurs in humans (who are henceforth called “women,” a word describing culture as well as biology), old-world apes, and few other mammals. By current concepts, women’s menstrual cycles provide estrogen for thirty to fifty years; following one year of no flow they become menopausal and “estrogen deficient.” By contrast we now know that the purpose of menstrual cycles is to supply all cells and tissues with the balanced essential actions of estradiol (E2) and progesterone (P4) produced in feedback-controlled patterns to facilitate fecundability and preserve younger women’s well-being. We also now know that menopausal women’s health is negatively affected (by increased osteoporosis, heart disease, breast and endometrial cancers) if those past menstrual cycles produced inadequate net P4 to counterbalance and complement E2’s actions. Menstrual periodicity, flow, and ovulatory characteristics in women reflect the integrated actions/interactions of the central nervous system through the hypothalamus and pituitary, ideally leading to each cycle’s stimulation of a dominant egg-containing follicle. That follicle, by central complex feedback loops, produces the cyclic, graded amounts of estradiol (E2) and progesterone (P4) for that threeto five-week period and releases a viable egg. Central reproductive connections allow adult premenopausal women’s menstrual cycle periodicity, ovulation or not, and luteal phase lengths, that can be adapted to the challenges and demands of each woman’s current physiological and sociocultural/emotional environments. These new ideas are based on the differing and complementary cellular and tissue actions of E2 and P4. E2 is essential for cell growth and stimulates cell proliferation. P4 uniquely counterbalances and controls proliferation while stimulating cell differentiation and tissue maturation. Thus, E2–P4 actual and relative productions integrate cycles within each woman’s reproductive lifecycle (adolescent, premenopausal, perimenopausal), and are related to her nutrition, illness, energy expenditure, and social/emotional/spiritual environments. The subtlest indication of a stressed reproductive system is truncated P4 production in the short luteal phase within a normal-length, ovulatory menstrual cycle. This adaptation protects a woman from pregnancy when she has inadequate net energy balance or is under emotional/social/spiritual or physical duress. Thus, a normal luteal phase length within a threeto five-week regular menstrual cycle is a bellwether of women’s well-being. By contrast, regular cycles with ovulatory disturbances (anovulation or short luteal phases; E2>P4) predict current decreased well-being and poor later life health. The purpose of this review is to provide a practical approach to understanding this new women’s menstrual cycle balanced E2–P4 paradigm applied to common clinical situations including subfertility with regular cycles, premenstrual symptoms, and heavy menstrual flow.

The Cambridge Handbook of Evolutionary Perspectives on Sexual Psychology


A comparison of app-defined fertile days from two fertility tracking apps using  identical cycle data

Abstract:
Objective: The Natural Cycles app employs daily basal body temperature to define the fertile window via a proprietary algorithm and is clinically established effective in preventing pregnancy. We sought to (1) compare the app-defined fertile window of Natural Cycles to that of CycleProGo, an app that uses BBT and cervical mucus to define the fertile window and (2) compare the app-defined fertile windows to the estimated physiologic fertile window.

Study Design: Daily BBT were entered into Natural Cycles from 20 randomly selected regularly cycling women with at least 12 complete cycles from the CycleProGo database. The proportion of cycles with equivalent (±1 cycle day) fertile-window starts and fertile-window ends was determined. The app-defined fertile windows were then compared to the estimated physiologic fertile window using Peak mucus to estimate ovulation.

Results: Fifty seven percent of cycles (136/238) had equivalent fertile-window starts and 36% (72/181) had equivalent fertile-window end days. The mean overall fertile-window length from Natural Cycles was 12.8 days compared to 15.1 days for CycleProGo (p < 0.001). The Natural Cycles algorithm declared 12% to 30% of cycles with a fertile-window start and 13% to 38% of cycles with a fertile-window end within the estimated physiologic fertile window. The CycleProGo algorithm declared 4% to 14% of cycles with a fertile-window start and no cycles with a fertile-window end within the estimated physiologic fertile window.

Conclusions: Natural Cycles designated a higher proportion of cycles days as infertile within the estimated physiologic fertile window than CycleProGo.
Implications: Use of cervical mucus in addition to BBT may improve the accuracy of identifying the fertile window. Additional studies with other markers of ovulation and the fertile window would give additional insight into the clinical implications of app-defined fertile window differences.


Natural Family Planning, An Option in Reproductive Healthcare: A Qualitative  Study on Clinicians' Perceptions

Abstract: Natural family planning (NFP) empowers women to control their reproductive health and approach fertility as a normal biological process. Although substantive literature supports their comparative effectiveness with contraceptive methods, there is a paucity of this knowledge amongst clinicians and users. This study aimed to understand clinicians' perceptions regarding offering NFP to patients as part of reproductive health care. It explored clinicians' knowledge of NFP, described their perceptions of their effectiveness, and identified enabling and deterring factors to their use. Basic Interpretive qualitative research design was appropriate in obtaining an in-depth description of this phenomenon. It was conducted in 2018 in two hospitals and clinics in Ekurhuleni health district, located East of Gauteng Province, South Africa. Fifteen doctors and nurses from diverse cultural and educational backgrounds were purposefully selected and interviewed. Transcribed data were analyzed, coded, and recurrent themes identified. Training that empowers clinicians on NFP methods and their effectiveness will improve their willingness to advocate for it and promote patient autonomy by providing comprehensive counseling on family planning methods. Further, a pro-NFP policy would drive training in undergraduate and postgraduate programs and increase public awareness, including early education of male and female children.


Reproductive Services and Conscience-Based Refusals in Obstetrics and Gynecology  Training

Cara Buskmiller

Department of Obstetrics, Gynecology, and Women’s Health, St. Louis University, St. Louis, MO, USA

Abstract:
Purpose: Professional bodies such as the American College of Obstetrics and Gynecology recognize the impact of conscience-based decisions. The first time such decisions affect patients and providers is in residency. Our study sought to determine the attitudes of program directors towards various conscience-based refusals in potential applicants to obstetrics and gynecology programs. Method: An eight-question survey was sent to 279 directors of U.S. obstetrics and gynecology residencies in 2019. The survey proposed hypothetical conscientious refusals of common aspects of obstetric and gynecology practice. The survey asked respondents to categorize their reaction to these choices and choose from a list of factors which could modify their reaction. Univariate analysis and multivariate logistic regression were performed.

Results: 97 program directors (35%) responded. A majority of PDs reported that the inability to prescribe or counsel on birth control, to provide methotrexate, to counsel on abortion, or to clearly enumerate refusals was impossible to work around, likely to lower an applicant's rank, not compatible with training, or not good for patients; collectively, these responses were grouped as "negative reactions" (73-99%). Female program directors had more negative reactions to applicants who refused to prescribe birth control (aOR 15.8, 95% CI 1.7-99.5) and counsel on abortion (aOR 3.6, 95% CI 1.2-10.8). Directors from different locations and program types did not have significantly different responses. A few program directors identified that academic strength could mitigate otherwise negatively-viewed choices. Illustrative comments of directors' attitudes are provided.

Conclusions: Program directors agree that conscientious refusal to participate in certain activities is problematic for obstetrics and gynecology residency. There are very few subjective or regional differences on this stance, and few aspects of an application modify directors' reactions.


He's Yangchao Recipe Ameliorates Ovarian Oxidative Stress of Aging Mice under

Abstract:
Objective: To evaluate the effects of He's Yangchao Recipe (HSYC) on ameliorating ovarian oxidative stress of aging mice under consecutive superovulation.

Methods: An 8-month-old C57BL/6 female mouse was chosen to establish an aging model under ovarian hyperstimulation. Mice were randomly separated into four groups: R1 as the control group, R4 as the model group, NR4 with N-acetyl-L-cysteine (NAC) administration, and TR4 with HSYC administration. Oocyte collection, in vitro fertilization, and embryo culture were performed. The serum hormone levels were measured by enzyme-linked immunosorbent assays (ELISA); the reactive oxygen species (ROS) level of oocytes, the number of growing follicles, corpus luteum, ovulated oocytes, and developing embryos at each stage, along with the proportions of fragmented oocytes and abnormal mitochondria in granulosa cells (GCs) and the apoptosis rate of GCs were calculated; the mRNA and protein levels of JNK, P53, BAX were detected by real-time PCR and the Simple Western System.

Results: HSYC enhanced estradiol, progesterone, and inhibin-B levels and increased growing follicle and corpus luteum and ovulated egg counts compared to the R4 group (P < 0.05), whereas it decreased the proportions of fragmented oocytes (P < 0.01); Meanwhile, embryos from mice subjected to four superovulation cycles with HSYC treated had a higher hatching potential. The ROS level of oocytes is downregulated by HSYC (P < 0.01) and the percentage of abnormal mitochondrial in ovaries of the TR4 group was also significantly declined compared to the R4 group (P < 0.05); the most TUNEL-positive cells proportion was detected in the R4 group; nevertheless, HSYC effectively attenuated this detrimental effect (P < 0.05). The mRNA and protein expressions of JNK and P53 in ovary tissues were reduced in the TR4 group while these genes were upregulated by repeated superovulation (P < 0.05).

Conclusions: HSYC exerted promising effects on promoting the diminished ovarian reserve and decreased oocyte quality induced by both aging and consecutive ovarian superovulation, potentially via the ROS/JNK/p53 pathway.

Evidence-based Complementary and Alternative Medicine : eCAM


Evidence based recommendations for an optimal prenatal supplement for women in the US: vitamins and related nutrients

Abstract: The blood levels of most vitamins decrease during pregnancy if un-supplemented, including vitamins A, C, D, K, B1, B3, B5, B6, folate, biotin, and B12. Sub-optimal intake of vitamins from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of vitamins is often below recommended intakes, especially for vitamin D, choline and DHA. Many studies suggest that insufficient vitamin intake is associated with a wide range of pregnancy complications (anemia, Cesarean section, depression, gestational diabetes, hypertension, infertility, preeclampsia, and premature rupture of membranes) and infant health problems (asthma/wheeze, autism, low birth weight, congenital heart defects, intellectual development, intrauterine growth restriction, miscarriage, neural tube defects, orofacial defects, and preterm birth). The primary goal of this paper is to review the research literature and propose evidence-based recommendations for the optimal level of prenatal supplementation for each vitamin for most women in the United States. A secondary goal was to compare these new recommendations with the levels of vitamins in over 180 commercial prenatal supplements. The analysis found that prenatal supplements vary widely in content, often contained only a subset of essential vitamins, and the levels were often below our recommendations. This suggests that increasing prenatal vitamin supplementation to the levels recommended here may reduce the incidence of many pregnancy complications and infant health problems which currently occur.

Maternal health, neonatology and perinatology


'Seeing is believing': arguing for diagnostic laparoscopy as a diagnostic test  for endometriosis

Jason Mak

Acute Gynaecology, Early Pregnancy and Advanced Endosurgery Unit, Nepean Hospital, Sydney Medical School Nepean, University of Sydney, Sydney, New South Wales, Australia

Abstract: Endometriosis is a benign disease that can cause pain and infertility in women. Debate exists over how endometriosis should best be diagnosed. On one hand, endometriosis can be diagnosed by directly examining pelvic anatomy via a surgical procedure known as diagnostic laparoscopy. On the other hand, the disease can be diagnosed via non-surgical means such as using medical imaging, the symptoms described by the patient and whether the patient responds to non-surgical therapies such as medication. In this debate article, we argue in favour of diagnostic laparoscopy. We review the safety of the procedure, compare the ability of diagnostic laparoscopy vs medical imaging to detect endometriosis and consider the benefits of formally diagnosing or ruling out the condition.


Vitamin D and miscarriage: a systematic review and meta-analysis

Arri Coomarasamy

Birmingham Women’s and Children’s NHS Foundation Trust

Abstract:
OBJECTIVE: To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists.

DESIGN: Systematic review and meta-analysis.

SETTING: Not applicable.

PATIENT(S): Women with miscarriage and RM.

INTERVENTION(S): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included.

MAIN OUTCOME MEASURE(S): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed.

RESULT(S): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I2 = 18%). Combined analysis, including women who were vitamin D insufficient (50-75 nmol/L) and deficient (<50 nmol/L) compared with women who were replete (>75 nmol/L), found an association with miscarriage (odds ratio, 1.60; 95% confidence interval, 1.11-2.30; 6 studies; n = 6,338; I2 = 35%). Although 4 randomized controlled trials assessed the effect of vitamin D treatment on miscarriage, study heterogeneity, data quality, and reporting bias precluded direct comparison and meta-analysis. The overall study quality was "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach.

CONCLUSION(S): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown.

REGISTRATION NUMBER: CRD42021259899.


Access to Fertility Care in Geographically Underserved Populations, a Second Look

Navid Esfandiari

Toronto Centre for Advanced Reproductive Technology, Toronto, Ontario, Canada. ; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Toron...

Abstract: Infertility has a prevalence of up to 16% worldwide and is on the rise in developed nations, largely due to pursuing childbearing at advanced reproductive ages. Advances in assisted reproductive technology have benefitted socioeconomically advantaged patients disproportionately. High costs of fertility care are largely responsible for this disparity; however, patients in rural areas also face barriers in accessing both gynecology and reproductive endocrinology subspecialty care. Here, focusing on the USA, we discuss fertility care in geographically underserved areas and low-resource settings, and the impact on reproductive outcomes. Increased innovation to improve patient access to fertility care such as assisted reproductive technology is critical for ensuring equity. Remote monitoring is frequently performed by fertility centers, but partnership with local gynecologists has also been demonstrated to be an effective assisted reproductive technology monitoring method. Telehealth is now in mainstream use and the continued application to reduce geographic barriers to infertility patients is imperative. Partnership between local gynecologists and reproductive endocrinology and infertility specialists may improve patient access to fertility care and provide the unique benefits of continuity and ongoing local social support.

Reproductive sciences (Thousand Oaks, Calif.)


Transcutaneous electrical neurostimulation relieves primary dysmenorrhea: A randomized, double-blind clinical study versus placebo

Abstract:
INTRODUCTION: This randomized, crossover, double-blind, controlled trial evaluates the efficacy and safety of a preprogrammed transcutaneous electrical nerve stimulation (TENS) device versus placebo (SHAM) in women with primary dysmenorrhea (PD).

MATERIAL: Forty women suffering from significant dysmenorrhea requiring the use of analgesics and/or non-steroidal anti-inflammatory drugs self-apply to the abdominal or lumbar region depending on the location of the pain, alternately according to randomization, the TENS device then the SHAM (dummy device) or conversely SHAM then TENS. The primary endpoint compares the evolution of pain intensity before and after application of TENS and SHAM. The speed of action, the persistence of the analgesic effect and the therapeutic savings are also evaluated. Adverse events (AEs) are collected.

RESULTS: A statistically and clinically significant decrease in the pain of 53% (P<0.0001) is observed during the first 2 applications of TENS versus no analgesic effect (-5%, P=0.318) with SHAM. Over all 197 applications of TENS, the reduction of menstrual pain intensity by more than half is confirmed. The rapid relief, less than 20 minutes in 74% of cases, lasts on average more than 7 hours. A difference in analgesic consumption of -93% is observed in favor of TENS (P<0.01). Seven participants reported 10 non-serious AEs, 2 of which were possibly related to TENS.

CONCLUSION: The TENS device tested represents a well-tolerated, rapidly and lastingly effective non-pharmacological analgesic solution, capable of replacing or being combined with analgesics in the management of PD.

Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie


Chronic endometritis: A prevalent yet poorly understood entity

Abstract:
OBJECTIVE: To examine the prevalent understanding of and management approaches to chronic endometritis among obstetricians/gynecologists.

METHODS: In a cross-sectional observational study, 262 members of national and international professional obstetrician/gynecologist societies were surveyed via anonymous electronic survey that investigated knowledge of the pathophysiology, diagnostic criteria, clinical implications, and treatment strategies for chronic endometritis. Statistical analyses of results were performed using Fisher's exact tests, chi square tests and odds ratios with 95% confidence intervals. A two-sided P < 0.05 was deemed statistically significant.

RESULTS: Responses identified a concerning spectrum of deficiencies in the understanding of the pathophysiology of chronic endometritis, in awareness of clinical presentation of chronic endometritis, and in the understanding of methodology/ies that allow diagnosis of chronic endometritis. Heterogeneities in management approaches to chronic endometritis were apparent.

CONCLUSION: Our findings underscore a need for targeted efforts to gain clarity on chronic endometritis and to establish evidence-based consensus for good clinical practice. In the absence of a clear understanding of chronic endometritis diagnosis, we posit that the prevalent inconsistencies are likely inflicting unquantified and underappreciated burdens on patients and healthcare systems. We propose consideration for a task force to examine existing literature and create standards for good practice for a prevalent condition.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics


Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health

Integrative medicine (Encinitas, Calif.)


Male Infertility Increases the Risk of Cardiovascular Diseases: A Nationwide Population-Based Cohort Study in Taiwan

Yin Ju Chen

Institute of Molecular Biology, Academia Sinica

Chang-Chang Huang

Second Affiliated Hospital of Zhejiang University

Abstract:
PURPOSE: Some evidence suggests that male infertility increases the risk of cardiovascular diseases (CVDs). However, the evidence in Asian populations is relatively scarce. The aim of this study is to determine whether male infertility increases the risk of CVDs.

MATERIALS AND METHODS: We used inpatient and outpatient data for the years 2000 to 2015 from the Taiwanese Longitudinal Health Insurance Database. We enrolled 7,016 males over 18 years old and diagnosed with male infertility. Of these, 2,326 matched our inclusion criteria and were assigned to the study group. For each infertility patient, four comparison patients were frequency-matched by age and index date to form a control cohort comprising 9,304 patients. Cox proportional hazards analysis was used to estimate the association between male infertility and CVDs.

RESULTS: After a 15-year follow-up, the incidence rate of CVDs was higher in the infertility group than the control group (1,460.23 and 1,073.70 per 100,000 person-years, respectively). The Cox proportional hazards regression analysis revealed that the adjusted HR for CVDs was 1.472 for the infertility group (95% CI, 1.288-1.683; p<0.001) relative to the control group. The Kaplan-Meier analysis of the cumulative incidence of CVDs in the two groups showed that the cumulative risk curve for CVDs was significantly higher for the infertility group than the control group.

CONCLUSIONS: This study shows that men with infertility have a higher risk of developing incident CVDs. In the future, healthcare providers should pay attention to these patients because of their higher health risks.


The 2022 hormone therapy position statement of The North American Menopause Society

“The 2022 Hormone Therapy Position Statement of The North American Menopause Society” Advisory Panel

Abstract: "The 2022 Hormone Therapy Position Statement of The North American Menopause Society" (NAMS) updates "The 2017 Hormone Therapy Position Statement of The North American Menopause Society" and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2017 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Advisory Panel's recommendations were reviewed and approved by the NAMS Board of Trustees.Hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing therapy.For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome VMS and prevention of bone loss. For women who initiate hormone therapy more than 10 years from menopause onset or who are aged older than 60 years, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS, with shared decision-making and periodic reevaluation. For bothersome genitourinary syndrome of menopause symptoms not relieved with over-the-counter therapies in women without indications for use of systemic hormone therapy, low-dose vaginal estrogen therapy or other therapies (eg, vaginal dehydroepiandrosterone or oral ospemifene) are recommended.


Evaluation of Sperm Selection Technique Using Hyaluronic Acid Binding During Icsi; a Randomized Controlled Trial

Abstract: In-vitro sperm selection for intracytoplasmic sperm injection (Physiological ICSI or PICSI) is crucial as it has a direct influence on the paternal contribution of preimplantation embryogenesis. Men with oligozoospermia who require ICSI often demonstrate compromised DNA integrity and increased chromosomal aberrations of the sperms in their semen. Studies have shown that embryos resulting from ICSI in those men have higher risk of sex chromosome disomies, chromosomal aneuploidies, de novo numerical chromosomal aberrations and cytogenetically detectable structural chromosomal aberrations. Although the primary candidates for ICSI are oligozoospermic men, there is an increase in the use of ICSI; therefore, more couples are potentially exposed to those potential risks.

Obstetrics Gynecology and Reproductive Sciences


Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy  and Live Birth Rates in ART: Systematic Review and Meta-Analyses

Stephanie Huberlant

Centre Hospitalier Universitaire de Nîmes

Marie Montagut

Center for Human Reproduction-Institut Francophone de Recherche Et d'études Appliquées à la Reproduction Et Sexologie (IFREARES), Clinique Saint Jean du Languedoc, Toulouse, France.

Abstract: Progesterone plays a key role in implantation. Several studies reported that lower luteal progesterone levels might be related to decreased chances of pregnancy. This systematic review was conducted using appropriate key words, on MEDLINE, EMBASE, and the Cochrane Library, from 1990 up to March 2021 to assess if luteal serum progesterone levels are associated with ongoing pregnancy (OP) and live birth (LB) rates (primary outcomes) and miscarriage rate (secondary outcome), according to the number of corpora lutea (CLs). Overall 2,632 non-duplicate records were identified, of which 32 relevant studies were available for quantitative analysis. In artificial cycles with no CL, OP and LB rates were significantly decreased when the luteal progesterone level falls below a certain threshold (risk ratio [RR] 0.72; 95% confidence interval [CI] 0.62-0.84 and 0.73; 95% CI 0.59-0.90, respectively), while the miscarriage rate was increased (RR 1.48; 95% CI 1.17-1.86). In stimulated cycles with several CLs, the mean luteal progesterone level in the no OP and no LB groups was significantly lower than in the OP and LB groups [difference in means 68.8 (95% CI 45.6-92.0) and 272.4 (95% CI 10.8-533.9), ng/ml, respectively]. Monitoring luteal serum progesterone levels could help in individualizing progesterone administration to enhance OP and LB rates, especially in cycles without corpus luteum. SYSTEMATIC REVIEW Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139019, identifier 139019.


Robot-assisted laparoscopy repair of uterine isthmocele: A two-center  observational study

Claire Cardaillac

Centre Hospitalier Universitaire de Nantes

Krystel Nyangoh Timoh

Centre Hospitalier Universitaire de Rennes

Abstract:
Objective: To analyze outcomes and postoperative complications in patients undergoing robot-assisted isthmocele repair. METHOD: This retrospective cohort study included 33 patients who had robot-assisted laparoscopic surgical management of an isthmocele between September 2013 and August 2020 in two French university hospitals. All charts were reviewed to identify patient characteristics, preoperative and postoperative anatomical findings, complications, and postoperative fertility and symptoms. Patients who had undergone this procedure were asked to complete a telephone questionnaire about their treatment satisfaction and symptoms.

Results: The isthmocele was discovered most often as a result of subfertility (57.6%), but also ectopic pregnancy (18.2%), pelvic pain (15.2%), and postmenstrual bleeding (9.1%). Robot-assisted repair of the isthmocele significantly improved myometrial thickness (from 1.55 mm before surgery to 4.26 mm after surgery [mean difference 2.71; 95% confidence interval, 1.91-3.51], P = 0.0005). Among 20 patients who still desired a child after surgery, 15 became pregnant and 14 had full-term live births. Among the nine patients who had surgery for disabling symptoms, five had no persistent symptoms, three reported global improvement, and one had the same gynecologic discomfort. Seventeen patients agreed to complete the questionnaires (51.5%), and all stated that they would choose to have this surgery again.

Conclusion: Robot-assisted repair of an isthmocele is a viable minimally invasive procedure.

International Journal of Gynaecology and Obstetrics: the Official Organ of the  International Federation of Gynaecology and Obstetrics


Successful pregnancy with restorative reproductive medicine after 16 years of infertility, three recurrent miscarriages, and eight unsuccessful embryo transfers with in vitro fertilization/intracytoplasmic sperm injection: a case report

Phil C Boyle

NeoFertility Clinic, Suite 7, 1st Floor, Beacon Mall, Sandyford, Dublin 18, Ireland. Phil.Boyle@NeoFertility.ie.

Abstract:
BACKGROUND: Restorative reproductive medicine represents a comprehensive approach to subfertility (infertility and miscarriage) with investigations, diagnoses, and treatments combined with fertility charting to restore optimal reproductive function. Restorative reproductive medicine assumes that multiple factors need to be identified and treated (cycle optimization) for up to 12 cycles to achieve a successful pregnancy. Conception can occur during normal intercourse without intrauterine insemination or in vitro fertilization.

CASE PRESENTATION: A 35-year-old Croatian female presented for fertility treatment in May 2019 with a previous diagnosis of polycystic ovaries, infertility of 16 years duration, and 8 unsuccessful embryo transfers with in vitro fertilization and intracytoplasmic sperm injection. She was gravida 3 para 0, with 2 miscarriages after spontaneous conception at 5-6 weeks gestation in 2002 and 2004, followed by a miscarriage after in vitro fertilization at 12 weeks gestation in 2011. We initially found poor follicle function and suboptimal progesterone levels. Restorative reproductive medicine treatment resulted in conception after two cycles of treatment. This pregnancy ended in miscarriage at 7 weeks 4 days. Additional investigations found a balanced Robertsonian translocation (13, 14) and a uterine septum. We achieved repeat fertilization with restorative reproductive medicine after three cycles of treatment following resection of the uterine septum and ovulation induction with letrozole and human chorionic gonadotrophin. She had a full-term healthy pregnancy and live birth in 2021.

CONCLUSION: We propose that a full evaluation of underlying factors, and up to 12 cycles of cycle optimization, should be offered to subfertile patients before considering in vitro fertilization treatment.


Menstrual Cycle Parameters Are Not Significantly Different After COVID-19  Vaccination

Abstract:
Background: Some studies have suggested minor changes in the menstrual cycle after COVID-19 vaccination, but more detailed analyses of the menstrual cycle are needed to evaluate more specific changes in the menstrual cycle that are not affected by survey-based recall bias.

Materials and Methods: Using a pretest-post-test quasi-experimental evaluation of menstrual cycle parameters before and after COVID-19 vaccination, we conducted an anonymous online survey of two groups of North American women who prospectively monitor their menstrual cycle parameters daily including bleeding patterns, urinary hormone levels using the ClearBlue Fertility Monitor, or cervical mucus observations. The primary outcome measures were cycle length, length of menses, menstrual volume, estimated day of ovulation (EDO), luteal phase length, and signs of ovulation. Perceived (subjective) menstrual cycle changes and stressors were also evaluated in this study as secondary outcome measures.

Results: Of the 279 women who initiated the survey, 76 met the inclusion criteria and provided 588 cycles for analysis (227 pre-vaccine cycles, 145 vaccine cycles, 216 post-vaccine cycles). Although 22% of women subjectively identified changes in their menstrual cycle, there were no significant differences in menstrual cycle parameters (cycle length, length of menses, EOD, and luteal phase length) between the pre-vaccine, vaccine, and post-vaccine cycles.

Conclusions: COVID-19 vaccines were not associated with significant changes in menstrual cycle parameters. Perceived changes by an individual woman must be compared with statistical changes to avoid confirmation bias.


Effectiveness of fertility awareness-based methods for pregnancy prevention  during the postpartum period

Margaret E Greene

GreeneWorks, Washington DC, United States.

Emily Kennedy

The Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, United States.

James J Redmond

Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States.

Abstract:
Objectives: To summarize the evidence on typical and perfect-use effectiveness of fertility awareness-based methods for avoiding pregnancy during the postpartum period, whether breastfeeding or not.

Study Design: We conducted a systematic review of studies published in English, Spanish, French, or German by November 2021 in MEDLINE, EMBASE, CINAHL, Web of Science, and ClinicalTrials.gov. Abstract and full text reviews were completed by 2 independent reviewers. Study inclusion: at least 50 subjects who enrolled prior to experiencing 3 cycles after childbirth and were using a specific fertility awareness-based method to avoid pregnancy; unintended pregnancy rate or probability calculated; postpartum amenorrheic and postpartum cycling individuals analyzed separately; and prospectively measured pregnancy intentions and outcomes. Outcomes were abstracted and study quality was systematically assessed by 2 independent investigators.

Results: Four studies provided effectiveness data for 1 specific fertility awareness-based method among postpartum individuals. Of these, there were zero high quality, 1 moderate quality, and 3 low quality for our question of interest. Typical-use pregnancy probability for the first 6 cycles postpartum for Marquette Method users was 12.0 per 100 women years (standard error [SE] not reported) and for Billings Ovulation Method users ranged from 9.1 (SE 3.9) for non-lactating women <30 years old to 26.8 (SE 4.6) for lactating women <30 years old. Typical-use pregnancy probabilities for the first 6 months post-first menses for the Postpartum Bridge to Standard Days Method users was 11.8 (95% confidence interval 6.01-17.16) and for Billings Ovulation Method users was 8.5 per 100 women (SE 1.7).

Conclusion: The current evidence on the effectiveness of each fertility awareness-based method for postpartum persons is very limited and of mostly low quality. More high quality studies on the effectiveness of fertility awareness-based method in postpartum persons are needed to inform clinical counseling and patient-centered decision-making.
Implications: Although postpartum individuals may desire to use fertility awareness-based methods to avoid pregnancy, the evidence of the effectiveness of fertility awareness-based methods in this population is limited. More high-quality studies are needed to inform shared decision-making.


Analysis of risk factors associated with breast cancer in women: a systematic  review and meta-analysis

Suling Shi

First Affiliated Hospital of Henan University of Science and Technology

Abstract:
Background: The aim of the present study was to explore the risk factors and protective factors related to breast cancer onset in women, but there is still a big debate in this respect. Therefore, it is necessary to systematically review the risk factors induced by breast cancer by using meta methods to guide clinical prevention and treatment.

Methods: Studies on factors related to breast cancer onset in Chinese women were retrieved from articles from Chinese, international databases published and organizations and websites, and registers from January 2014 to January 2021. Articles were independently screened, extracted, and evaluated for quality by 2 researchers. The Cochrane Collaboration Center provided Review Manger 5.2 software [Cochrane Information Management System (IMS)] for statistical analysis, and the risk ratio of dichotic variables was adopted.

Results: History of benign breast disease [odds ratio (OR) 1.03, 95% confidence interval (CI): 0.95-1.12, P=0.42], family history of breast cancer (OR: 2.02, 95% CI: 1.83-2.23, P<0.00001), menopause onset >50 years of age (OR: 1.78, 95% CI: 1.62-1.95, P<0.00001), and use of oral contraceptives (OR: 1.16, 95% CI: 1.02-1.32, P=0.02) were found to be breast cancer risk factors. The number of term pregnancies (OR: 0.80, 95% CI: 0.66-0.97, P=0.03) and breastfeeding (OR: 0.84, 95% CI: 0.74-0.96, P=0.01) were found to be protective factors for breast cancer.

Conclusions: In order to control the occurrence of breast cancer, effective measures should be taken to effectively avoid related risk factors, and breastfeeding and high-risk population screening should be advocated.


The effect of medication on serum anti-müllerian hormone (AMH) levels in women of  reproductive age: a meta-analysis

Wei-Wei Yin

Second Affiliated Hospital of Zhejiang University

Abstract:
Objective: The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET).

Methods: Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis.

Results: After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001).

Conclusions: Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.


The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities


Fertility Awareness-Based Methods for Women's Health and Family Planning

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract:
Background: Fertility awareness-based methods (FABMs) educate about reproductive health and enable tracking and interpretation of physical signs, such as cervical fluid secretions and basal body temperature, which reflect the hormonal changes women experience on a cyclical basis during the years of ovarian activity. Some methods measure relevant hormone levels directly. Most FABMs allow women to identify ovulation and track this "vital sign" of the menstrual or female reproductive cycle, through daily observations recorded on cycle charts (paper or electronic). APPLICATIONS: Physicians can use the information from FABM charts to guide the diagnosis and management of medical conditions and to support or restore healthy function of the reproductive and endocrine systems, using a restorative reproductive medical (RRM) approach. FABMs can also be used by couples to achieve or avoid pregnancy and may be most effective when taught by a trained instructor. CHALLENGES: Information about individual FABMs is rarely provided in medical education. Outdated information is widespread both in training programs and in the public sphere. Obtaining accurate information about FABMs is further complicated by the numerous period tracking or fertility apps available, because very few of these apps have evidence to support their effectiveness for identifying the fertile window, for achieving or preventing pregnancy.

Conclusions: This article provides an overview of different types of FABMs with a published evidence base, apps and resources for learning and using FABMs, the role FABMs can play in medical evaluation and management, and the effectiveness of FABMs for family planning, both to achieve or to avoid pregnancy.


Chronic Stress and Ovulatory Dysfunction: Implications in Times of COVID-19

Yanara A Bernal

Reproductive Health Research Institute, Santiago, Chile

Abstract: Stress is known to be associated with adverse health outcomes. The COVID-19 pandemic and its associated lockdowns are examples of chronic stressors. Lockdown measures inadvertently caused significant psychological distress and became a powerful source of anxiety/stress, sleep disturbances, nutritional changes and weight gain. Stress is known to impact women's health specifically, through hypothalamic-pituitary-gonadal (HPG) axis dysfunction and resultant ovulatory dysfunction. Such dysfunction may manifest in menstrual irregularities and/or infertility due to hypothalamic hypogonadism. Here, we review the key physiological mediators of stress and associated ovulatory dysfunction. The kisspeptinergic system is comprised of sets of neurons located in the hypothalamus, the rostral periventricular region of the third ventricle (RP3V) and the arcuate nucleus (ARC). This system links nutrition, reproductive signals and stress. It plays a key role in the function of the HPG axis. During chronic stress, the kisspeptinergic system affects the HPG axis, GnRH pulsatility, and, therefore, ovulation. Leptin, insulin and corticotrophin-releasing hormone (CRH) are thought to be additional key modulators in the behavioral responses to chronic stress and may contribute to stress-related ovulatory dysfunction. This mini-review also summarizes and appraises the available evidence on the negative impact of chronic stress as a result of the COVID-19 pandemic lockdowns. It proposes physiological mechanisms to explain the observed effects on women's reproductive health and well-being. The review suggests areas for future research.


Is There Still a Place for Reconstructive Surgery in Distal Tubal Disease?

Abstract: Tubal diseases account for 25-40% of female factor infertility. Mainly, they involve the distal part of the fallopian tube, and hydrosalpinx is the most severe manifestation. Usually, the management decision is made between reconstructive surgery and ART, depending on the severity of the tubal damage, patient age, ovarian reserve, and seminogram, as well as financial, religious, ethical, and psychological factors. Estimated live-birth rates after corrective surgery range from 9% to 69%. The success rate of IVF is about 30% live-birth rate per cycle initiated in women across all ages with tubal factor infertility. Surgery offers a long-term cure and patients may attempt conception many times but are burdened with perioperative adverse events. IVF bypasses potential complications of operative treatment; however, this has its own unique risks. The effectiveness of reconstructive surgery versus ART has not been adequately evaluated. The success of fertility management depends on a thorough interpretation of existing data and careful patient selection. The presented review provides updates on the most recent progress in this area.


Changes in the prevalence of polycystic ovary syndrome in China over the past  decade

Yang R, Li Q, Zhou Z, Qian W, Zhang J, Wu Z, Jin L, Wu X, Zhang C, Zheng B, Tan J, Hao G, Li S, Tian T, Hao Y, Zheng D, Wang Y, Norman RJ, Li R, Liu P, Qiao J

Abstract:
Background: Polycystic ovary syndrome (PCOS) has become a major international public health concern. However, because of controversy about the diagnostic criteria and patient selection, estimates of its absolute prevalence and change with time vary greatly.

Methods: We conducted two consecutive nationwide epidemiological surveys of the prevalence of PCOS in representative samples of reproductive-aged women in China in 2010 and 2020. Face-to-face interviews were performed by trained interviewers in each survey. All participants completed a questionnaire and underwent a physical examination, blood sampling, and transvaginal pelvic ultrasound. We assessed hyperandrogenism (H), chronic anovulation (O), and polycystic ovaries (P) to classify the presence of PCOS using the Rotterdam criteria. The prevalence of PCOS among reproductive-aged women was estimated after consideration of differential probabilities of selection and population distribution. We conducted a logistic regression analysis by using the probability of PCOS as a function of the survey year to acquire the trend information across the years.

Findings: 28,739 respondents completed the survey, including 15,924 in the previously published 2010 survey and 12,815 in the new 2020 survey. In 2020, 826 participants could be diagnosed as having PCOS, with a weighted prevalence of 7.8% (95%CI: 7.0%, 9.0%) among women aged 20-49 years, leading to an estimate of 24.0 million women of reproductive age affected by this condition in China as a whole. The estimated prevalence in 2020 was higher than that of a decade ago despite identical research methods suggesting a two-thirds increase over the study period. Women with PCOS in 2020 also appeared to have a more severe phenotype overall than those of a decade ago, possibly reflecting a significantly higher prevalence of obesity, hyperandrogenism, and infertility.

Interpretation: The prevalence of PCOS in Chinese women has increased significantly over the past 10 years. PCOS is a significant public health problem in women of reproductive age in China and national policy and guidelines should be re-examined in the light of the current data.

Funding: National Key R&D Program of China and the National Natural Science Foundation of China.

The Lancet Regional Health. Western Pacific


Goossens V; European IVF-monitoring Consortium (EIM); European Society of Human Reproduction and Embryology (ESHRE)

Abstract:
---
title: "ART in Europe, 2018: results generated from European registries by ESHRE"
source_file: "eshre-eim-2018-source.pdf"
journal: "Human Reproduction Open"
volume_pages: "pp. 1–20, 2022"
doi: "https://doi.org/10.1093/hropen/hoac022"
authors: "Wyns C, De Geyter C, Calhaz-Jorge C, Kupka MS, Motrenko T, Smeenk J, Bergh C, Tandler-Schneider A, Rugescu IA, Goossens V"
pages: 20
extracted_date: "2026-04-24"
figures_extracted: 9
tables_extracted: 5
review_flags: 0
---
---
title: "ART in Europe, 2018: results generated from European registries by ESHRE"
journal: "Human Reproduction Open"
pages: "1–20, 2022"
doi: "https://doi.org/10.1093/hropen/hoac022"
---


Comprehensive guidance for human embryology, andrology, and endocrinology laboratories: management and operations: a committee opinion

Practice Committees of the American Society for Reproductive Medicine (ASRM) and the Society for Reproductive Biologists and Technologists (SRBT). Electronic address: asrm@asrm.org

Abstract: This document is a comprehensive guidance for human embryology, andrology, and endocrinology laboratories. Universal guidance applicable to all laboratories includes requirements and recommendations for accreditation and staffing in the United States, and specific guidance is included for each laboratory specialty.


High risk and low prevalence diseases: Ovarian torsion

Abstract:
INTRODUCTION: Ovarian torsion is a rare, frequently misdiagnosed condition that carries with it a high rate of morbidity.

OBJECTIVE: This review highlights the pearls and pitfalls of ovarian torsion, including presentation, evaluation, and management in the emergency department (ED) based on current evidence.

DISCUSSION: Ovarian torsion is one of the most common gynecological surgical emergencies and occurs with complete or partial rotation of the ovary along the supporting ligaments, obstructing vascular flow. Several risk factors include the presence of an ovarian mass or cyst. The most common population affected includes reproductive aged women, though cases also occur in premenarchal females, pregnant women, and postmenopausal women. Abdominal or pelvic pain is common but is not always sudden in onset or severe. Nausea and vomiting occur in 70%. Ultrasound can assist with diagnosis, but a normal ultrasound examination cannot exclude the diagnosis. Computed tomography with intravenous contrast can assist with diagnosis. Treatment includes emergent gynecologic consultation for surgical detorsion, along with symptomatic therapy in the ED.

CONCLUSIONS: An understanding of ovarian torsion can assist emergency clinicians in diagnosing and managing this disease.

The American journal of emergency medicine


Hormonal contraception and mood disorders

Abstract: Hormonal contraception is known to precipitate or perpetuate depression in some patients. The link between oral contraceptive pills and depression relates to the amount and type of progestogen contained in these pills. Many of the older oral contraceptive pills, which contain ethinylestradiol, are linked to severe mood problems. Newer oral contraceptive pills containing physiological forms of oestrogen may be better tolerated with a purported weaker link to mood problems. Clinicians should consider the temporal relationship between the use of hormonal contraception and development of new or worsened depression or mood changes.


Endometriosis and Infertility: A Long-Life Approach to Preserve Reproductive  Integrity

Maria Elisabetta Coccia

Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy

Abstract: Laparoscopic surgery was originally considered the gold standard in the treatment of endometriosis-related infertility. Assisted reproductive technology (ART) was indicated as second-line treatment or in the case of male factor. The combined approach of surgery followed by ART proved to offer higher chances of pregnancy in infertile women with endometriosis. However, it was highlighted how pelvic surgery for endometriosis, especially in cases of ovarian endometriomas, could cause iatrogenic damage due to ovarian reserve loss, adhesion formation (scarring), and ischemic damage. Furthermore, in the last few years, the trend to delay the first childbirth, recent technological advances in ultrasound diagnosis, and technological progress in clinical and laboratory aspects of ART have certainly influenced the approach to infertility and endometriosis with, ART assuming a more relevant role. Management of endometriosis should take into account that the disease is chronic and involves the reproductive system. Consequently, treatment and counselling should aim to preserve the chances of pregnancy for the patient, even if it is not associated with infertility. This review will analyse the evolution of the management of infertility associated with endometriosis and propose an algorithm for treatment decision-making based on the most recent acquisitions.

International Journal of Environmental Research and Public Health


Infertility in Men: Advances towards a Comprehensive and Integrative Strategy for  Precision Theranostics

Abstract: Male infertility is an increasing and serious medical concern, though the mechanism remains poorly understood. Impaired male reproductive function affects approximately half of infertile couples worldwide. Multiple factors related to the environment, genetics, age, and comorbidities have been associated with impaired sperm function. Present-day clinicians rely primarily on standard semen analysis to diagnose male reproductive potential and develop treatment strategies. To address sperm quality assessment bias and enhance analysis accuracy, the World Health Organization (WHO) has recommended standardized sperm testing; however, conventional diagnostic and therapeutic options for male infertility, including physical examination and semen standard analysis, remain ineffective in relieving the associated social burden. Instead, assisted reproductive techniques are becoming the primary therapeutic approach. In the post-genomic era, multiomics technologies that deeply interrogate the genome, transcriptome, proteome, and/or the epigenome, even at single-cell level, besides the breakthroughs in robotic surgery, stem cell therapy, and big data, offer promises towards solving semen quality deterioration and male factor infertility. This review highlights the complex etiology of male infertility, especially the roles of lifestyle and environmental factors, and discusses advanced technologies/methodologies used in characterizing its pathophysiology. A comprehensive combination of these innovative approaches in a global and multi-centric setting and fulfilling the suitable ethical consent could ensure optimal reproductive and developmental outcomes. These combinatorial approaches should allow for the development of diagnostic markers, molecular stratification classes, and personalized treatment strategies. Since lifestyle choices and environmental factors influence male fertility, their integration in any comprehensive approach is required for safe, proactive, cost-effective, and noninvasive precision male infertility theranostics that are affordable, accessible, and facilitate couples realizing their procreation dream.


Maternity After Orthotopic Liver Transplantation: Can the Use of Biological Fertility Indicators Help? Our Own Experience and Literature-based Recommendations

Antonio Castillo

Cátedra Gianna Beretta para Estudios de Bioética, Sexualidad y Reconocimiento de la Fertilidad, Universidad Alfonso X el Sabio-Fundación COF Getafe, Boadilla del Monte, Spain.

Abstract: Over the last 5 decades, the fulfillment of maternity wishes in solid organ transplanted women has become a reality. Despite pregnancy contraindication in transplanted women during the early post-transplant period, such a condition can be overcome after 12 months if patients show a good clinical evolution and do not present other general pre-conceptional findings. This article presents the case report of a young female liver transplanted patient that used symptothermal method as a reliable family planning method. After her gestational contraindication was lifted, observation of biological fertility indicators and fertility-guided sexual intercourse helped her fulfill her maternity wish and conceive and carry out a healthy offspring. Based on this case and on the available bibliographic evidence, this paper reviews the potential implications of the use of this kind of approach as a safe and effective alternative to assisted reproduction technology in the management of potential infertility problems in the young female transplanted population, a population which according to literature has higher rates of unsuccessful parenthood and might also be more vulnerable to iatrogenicity of ovarian hyperstimulation process and to multiple pregnancy.


Endometriosis diagnosis, staging and typology and adverse pregnancy outcome  history

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Kristina Allen-Brady

Genetic Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Background: Women with endometriosis may have an increased risk of adverse pregnancy outcomes. Research has focused on infertility clinic populations limiting generalisability. Few studies report differences by endometriosis severity.

Objectives: We investigated the relationships between endometriosis diagnosis, staging and typology and pregnancy outcomes among an operative and population-based sample of women.

Methods: Menstruating women ages 18-44 years enrolled in the ENDO Study (2007-2009), including the operative cohort: 316 gravid women undergoing laparoscopy/laparotomy at surgical centres in Utah and California; and the population cohort: 76 gravid women from the surgical centres' geographic catchment areas. Pregnancy outcomes were ascertained by questionnaire and included all pregnancies prior to study enrolment. Endometriosis was diagnosed via surgical visualisation in the operative cohort and pelvic magnetic resonance imaging in the population cohort. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were estimated using generalised linear mixed models for pregnancy outcomes, adjusting for women's age at study enrolment and at pregnancy, surgical site, body mass index and lifestyle factors.

Results: Women in the operative cohort with visualised endometriosis (n = 109, 34%) had a lower prevalence of live births, aPR 0.94 (95% CI 0.85, 1.03) and a higher prevalence of miscarriages, aPR 1.48 (95% CI 1.23, 1.77) compared with women without endometriosis. The direction and magnitude of estimates were similar in the population cohort. Women with deep endometriosis were 2.98-fold more likely (95% CI 1.12, 7.95) to report a miscarriage compared with women without endometriosis after adjusting for women's age at study enrolment and at pregnancy, surgical site and body mass index. No differences were seen between endometriosis staging and pregnancy outcomes.

Conclusions: While there was no difference in number of pregnancies among women with and without endometriosis in a population-based sample, pregnancy loss was more common among women with endometriosis, notably among those with deep endometriosis.


Platelet Rich Plasma in Gynecology-Discovering Undiscovered-Review

Dominika Streit-Ciećkiewicz

nd Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland.

Magdalena Emilia Grzybowska

Department of Gynecology, Gynecologic Oncology and Gynecologic Endocrinology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland

Abstract: Regenerative medicine combines elements of tissue engineering and molecular biology aiming to support the regeneration and repair processes of damaged tissues, cells and organs. The most commonly used preparation in regenerative medicine is platelet rich plasma (PRP) containing numerous growth factors present in platelet granularities. This therapy is increasingly used in various fields of medicine. This article is a review of literature on the use of PRP in gynecology and obstetrics. There is no doubt that the released growth factors and proteins have a beneficial effect on wound healing and regeneration processes. So far, its widest application is in reproductive medicine, especially in cases of thin endometrium, Asherman's syndrome, or premature ovarian failure (POF) but also in wound healing and lower urinary tract symptoms (LUTS), such as urinary incontinence or recurrent genitourinary fistula auxiliary treatment. Further research is, however, needed to confirm the effectiveness and the possibility of its application in many other disorders.


Menstrual Cycle-Associated Changes in Micronutrient Biomarkers Concentration: A Prospective Cohort Study

Abstract: To evaluate variations in micronutrient biomarker concentrations and deficiencies across the menstrual cycle in a cohort of healthy women. This prospective cohort study was conducted among healthy women of reproductive age living in the State College area, Pennsylvania, (n = 45). Data collection occurred at the early follicular phase, the late follicular phase, and the midluteal phase. Fasting blood samples were collected to measure micronutrient biomarkers. At the early follicular phase, the mean ± SD concentrations for zinc, copper, magnesium, and retinol were 81.8 ± 16.2 µg/dL, 80.1 ± 12.8 µg/dL, 17.9 ± 1.4 mg/L, and 39.4 ± 9.3 µg/dL, respectively. The geometric mean (95% CI) for manganese, iron and ferritin concentrations were 1.51 [1.21, 1.87] µg/L, 106.7 [90.8, 125.4] µg/dL, and 26.4 [20.5, 34.0] µg/L, respectively. Mean concentrations of zinc and magnesium declined by 6.6% (p = 0.009) and 4.6% (p < 0.001) from the early follicular phase to the midluteal phase, respectively. Other biomarkers remained relatively constant across the cycle. At the early follicular phase, the prevalence of low serum concentrations for zinc, copper, magnesium, manganese, iron, and ferritin was 22%, 7%, 29%, 13%, 14%, and 28%, respectively. Also, in early follicular phase, 36% had anemia, and 13% specifically had iron deficiency anemia. The prevalence of magnesium deficiency was significantly higher at the midluteal phase vs. the early follicular phase (p = 0.025). Our study suggests that while many micronutrient concentrations are relatively constant across the menstrual cycle in healthy women, zinc and magnesium decline, and the prevalence of magnesium deficiency increases. Supplemental data for this article is available online at.

Journal of the American Nutrition Association