Contraceptive Effectiveness of an FDA-Cleared Birth Control App: Results from the  Natural Cycles U.S. Cohort

Jack T Pearson

Natural Cycles Nordic AB, Stockholm, Sweden

Simon P Rowland

Natural Cycles USA Corp, New York, New York, USA.

Juan Acuna

Khalifa University of Science and Technology

Kristina Gemzell-Danielsson

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

Abstract:
Background: Digital fertility awareness-based methods of birth control are an attractive alternative to hormonal or invasive birth control for modern women. They are also popular among women who may be planning a pregnancy over the coming years and wish to learn about their individual menstrual cycle. The aim of this study was to assess the effectiveness of the Natural Cycles app at preventing pregnancy for a cohort of women from the United States and to describe the key demographics of current users of the app in such a cohort.

Materials and Methods: This prospective real-world cohort study included users who purchased an annual subscription to prevent pregnancy. Demographics were assessed through answers to in-app questionnaires. Birth control effectiveness estimates for the entire cohort were calculated using 1-year pearl index (PI) and 13-cycle cumulative pregnancy probability (Kaplan-Meier life table analysis).

Results: The study included 5879 women who contributed an average of 10.5 months of data for a total of 5125 woman-years of exposure. The average user was 30 years old with a body mass index of 24 and reported being in a stable relationship. With typical use, the app had a 13-cycle cumulative pregnancy probability of 7.2% and a 1-year typical use PI of 6.2. When the app was used under perfect use, the PI was 2.0.

Conclusions: The data presented in this study give insights into the cohort of women using this app in the United States, and provide country-specific effectiveness estimates. The contraceptive effectiveness of the app was in line with previously published figures from Natural Cycles (PI of seven for typical use and two for perfect use).


Amniotic fluid embolism syndrome: analysis of the Unites States International  Registry

Roberto Romero

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Miranda Klassen

Amniotic Fluid Embolism Foundation, Vista, CA.

Christine Watters

Louisiana State University Health Sciences Center New Orleans

Abstract:
Background: Incidence, risk factors, and perinatal morbidity and mortality rates related to amniotic fluid embolism remain a challenge to evaluate, given the presence of differing international diagnostic criteria, the lack of a gold standard diagnostic test, and a significant overlap with other causes of obstetric morbidity and mortality.

Objective: The aims of this study were (1) to analyze the clinical features and outcomes of women using the largest United States-based contemporary international amniotic fluid embolism registry, and (2) to investigate differences in demographic and obstetric variables, clinical presentation, and outcomes between women with typical versus atypical amniotic fluid embolism, using previously published and validated criteria for the research reporting of amniotic fluid embolism.

Materials and Methods: The AFE Registry is an international database established at Baylor College of Medicine (Houston, TX) in partnership with the Amniotic Fluid Embolism Foundation (Vista, CA) and the Perinatology Research Branch of the Division of Intramural Research of the NICHD/NIH/DHHS (Detroit, MI). Charts submitted to the registry between August 2013 and September 2017 were reviewed, and cases were categorized into typical, atypical, non-amniotic fluid embolism, and indeterminate, using the previously published and validated criteria for the research reporting of AFE. Demographic and clinical variables, as well as outcomes for patients with typical and atypical AFE, were recorded and compared. Student t tests, χ(2) tests, and analysis of variance tables were used to compare the groups, as appropriate, using SAS/STAT software, version 9.4.

Results: A total of 129 charts were available for review. Of these, 46% (59/129) represented typical amniotic fluid embolism and 12% (15/129) atypical amniotic fluid embolism, 21% (27/129) were non-amniotic fluid embolism cases with a clear alternative diagnosis, and 22% (28/129) had an uncertain diagnosis. Of the 27 women misclassified as an amniotic fluid embolism with an alternative diagnosis, the most common actual diagnosis was hypovolemic shock secondary to postpartum hemorrhage. Ten percent (6/59) of the women with typical amniotic fluid embolism had a pregnancy complicated by placenta previa, and 8% (5/61) had undergone in vitro fertilization to achieve pregnancy. In all, 66% (49/74) of the women with amniotic fluid embolism reported a history of atopy or latex, medication, or food allergy, compared to 34% of the obstetric population delivered at our hospital over the study period (P < .05).

Conclusion: Our data represent a series of women with amniotic fluid embolism whose diagnosis has been validated by detailed chart review, using recently published and validated criteria for research reporting of amniotic fluid embolism. Although no definitive risk factors were identified, a high rate of placenta previa, reported allergy, and conceptions achieved through in vitro fertilization was observed.

American Journal of Obstetrics & Gynecology MFM


Postoperative Ultrasound as a Predictor of Newborn Function and Ambulation after  Open Fetal Myelomeningocele Repair

Cara Buskmiller

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

Allan Fisher

Department of Obstetrics, Gynecology, and Women's Health, St. Louis University, St. Louis, Missouri, USA.

Abstract:
Objective: Function of the lower extremities after prenatal myelomeningocele (MMC) repair is best assessed with ambulatory function at 30-36 months of age, but parents often ask about function before this milestone. Lower extremity movement can be assessed by ultrasound (US) and at the newborn exam (NE), but correlation between US, NE, and ambulation is not firmly established.

Methods: This was a retrospective correlation study of fetuses that underwent open prenatal MMC repair at SSM Cardinal Glennon Fetal Care Institute, St. Louis, MO, between January 2011 and June 2017. Movement at the ankles, knees, and hips was assessed by US after open repair on postoperative days (PODs) 0-5 and at 32 weeks gestation. NE was performed by physical therapy or neurosurgery within the first month of life, and pediatric follow-up between 30 and 36 months of age was obtained to document ambulation.

Results: Forty-two fetuses were included. Joint movement seen on US varied by POD: it was present on POD 1 in 7% of fetuses and 62% by POD 5. Degree of ventriculomegaly, lesion level, and lesion length did not have a significant effect on US, NE, or ambulation. Knee movement on POD 3 correlated with knee movement at NE (k = 0.58, p < 0.01), but only later knee movement correlated with ambulation (k = 0.28-0.46, p = 0.01). Hip movement at 32 weeks was the only single joint assessment that correlated with NE and ambulation (k = 0.45 and 0.46, p = 0.03 and 0.01, respectively).

Conclusion: Lower extremity movement increases between POD 1 and POD 5 in fetuses after open fetal MMC repair. Knee and hip movement on US at 32 weeks correlates with ambulation at 30-36 months. These data may inform counseling, and direct therapy and spark prospective investigations.


Factors affecting the success of fallopian tube recanalization in treatment of  tubal obstructive infertility

Mingjin Cai

Abstract:
Objective: To examine potential risk factors associated with the success rate following fallopian tube recanalization (FTR) in infertile women with obstruction of the proximal fallopian tube.

Methods: We retrospectively studied patients who underwent FTR for tubal obstructive infertility between January 2016 and December 2018 at the Third Affiliated Hospital of Guangzhou Medical University. FTR was performed using a catheter and guidewire system to clear tubal obstruction. Predictive factors potentially associated with the success rate were assessed by logistic regression.

Results: A total of 762 patients were included. Multivariable analysis showed that age (odds ratio [OR] = 2.38, 95% confidence interval [CI]: 1.24-4.58), infertility type (OR = 2.82, 95% CI: 1.36-6.21), history of ectopic pregnancy (OR = 7.87, 95% CI: 4.05-15.81), history of abdominal surgery (OR = 4.30, 95% CI: 2.22-8.60), history of artificial abortion curettage (OR = 4.08, 95% CI: 2.12-8.03), and duration of infertility (OR = 2.03, 95% CI: 1.06-3.85) were independently associated with postoperative tubal patency.

Conclusions: Our findings suggest that risk factors, such as age ≥35 years, secondary infertility, duration of infertility ≥5 years, and histories of ectopic pregnancy, abdominal surgery, and artificial abortion curettage, affect the success rate of FTR. These factors may also predict surgical success in treating tubal obstructive infertility.

The Journal of International Medical Research


Fertility and Reproduction after Recovery from Anorexia Nervosa: A Systematic Review and Meta-Analysis of Long-Term Follow-Up Studies

Abstract: Reproductive health is compromised during anorexia nervosa (AN). However, it is still unclear whether this medical complication is reversible after recovery from AN. The purpose of this paper was to conduct a systematic review of the major reproductive health outcomes in females after recovery from AN. The review was conducted in adherence to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Data were collated using meta-analysis and a narrative approach. Of the 1186 articles retrieved, five studies met the inclusion criteria and were reviewed. These studies monitored weight-restored females who had recovered from AN for a follow-up period of between six and 18 years. Their narrative analysis revealed that appropriate treatment of AN leads to the normalization of reproductive function, especially in terms of fertility, pregnancy, and childbirth rates. The meta-analysis confirmed this finding, where the pooled odds of childbirth rates between the AN group and the general population was not statistically significant (OR = 0.75, 95% CI: 0.43-1.29, p = 0.41). We conclude that if patients undergo appropriate eating-disorder treatment and weight restoration, it appears to be unlikely that reproductive health is affected by AN. However, since this finding is derived from only a few studies, it requires replication and confirmation.


Oral contraceptives and the serotonin 4 receptor: a molecular brain imaging study  in healthy women

K Köhler-Forsberg

Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.

P S Jensen

Neurobiology Research Unit Rigshospitalet Copenhagen Denmark

Abstract:
Objective: Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register-based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging.

Methods: [(11)C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions.

Results: We demonstrate that OC users have 9-12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (-12.8% (95% CI [-21.0; -3.9], P(corrected) = 0.03).

Conclusion: We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.


Pregnancy-induced long-term uterine vascular remodeling in the rat

Stephen Sammut

Department of Psychology, Franciscan University of Steubenville, 1235 University Blvd, Steubenville, OH, 43952, USA. Electronic address: ssammut@franciscan.edu.

Abstract: Despite the available research investigating uterine physiology during and immediately following pregnancy, including at the vascular and muscular levels, knowledge of the potential long-term timeline of such changes is limited. Thus, our study sought to investigate the potential long-term changes in uterine vasculature and horn length in the postpartum rat, following delivery and weaning. Female Long-Evans rats (n = 9-11 rats/group/timepoint) were divided into two groups: a pregnant group and an age-matched virgin control group. Rat weight, food consumption and vaginal impedance measurements were recorded throughout the experiment. Rats in the pregnant group were bred and pregnancy was confirmed using ultrasound imaging. The uterus and its vasculature were collected at various timepoints following weaning: 3 (week of weaning), 8-9 and 13 weeks postpartum, and at age-equivalent timepoints in the virgin group, and the diameters of the main uterine artery and vein, and lengths of the mesometrial segmental vessels (MSV) and uterine horns were recorded. The results indicated a significant difference between the previously-pregnant and virgin rats in both internal and external arterial diameters (but not arterial wall thickness), as well as the uterine horn length, 3 weeks postpartum, but not 8-9 and 13 weeks postpartum. Significant differences were observed in both venous diameter and MSV length at all timepoints measured. Placental scars were also observed in previously-pregnant rats at all timepoints measured. Our study highlights the long-term impact of pregnancy on the uterine vasculature and the necessity for consideration of such changes on subsequent pregnancies, as well as pregnancy-related vascular pathologies.


Developing a core outcome set for future infertility research: an international consensus development study

Duffy JMN, AlAhwany H, Bhattacharya S, Collura B, Curtis C, Evers JLH, Farquharson RG, Franik S, Giudice LC, Khalaf Y, Knijnenburg JML, Leeners B, Legro RS, Lensen S, Vazquez-Niebla JC, Mavrelos D, Mol BWJ, Niederberger C, Ng EHY, Otter AS, Puscasiu L, Rautakallio-Hokkanen S, Repping S, Sarris I, Simpson JL, Strandell A, Strawbridge C, Torrance HL, Vail A, van Wely M, Vercoe MA, Vuong NL, Wang AY, Wang R, Wilkinson J, Youssef MA, Farquhar CM

Abstract: STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the SPIRIT statement, and over 80 specialty journals, including Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.


2018 Assisted Reproductive Technology Fertility Clinic Success Rates Report

Abstract: The 2018 Assisted Reproductive Technology (ART) Fertility Clinic Success Rates Report, prepared under the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493), presents data submitted to the Centers for Disease Control and Prevention (CDC) by 456 reporting fertility clinics in the United States, Puerto Rico, and the District of Columbia for ART cycles initiated during the 2018 reporting year. The report includes 203,119 ART cycles, 73,831 live-birth deliveries, and 81,478 infants born through ART. Clinic-specific data are presented for each reporting clinic and include fresh and frozen ART cycles using patients' own eggs and donor eggs, broken out by patient age band (less than 35, 35 to 37, 38 to 40, 41 to 42, and over 42 years). The 2018 Report introduced data suppression rules to suppress the publication of small numbers (1 through 4) to reduce the risk of patient identification. The Report also presents national summary figures and clinic table summaries, including cumulative success rates that combine fresh and frozen embryo transfers from a single oocyte retrieval. CDC estimates that the proportion of all ART cycles reported to the National ART Surveillance System (NASS) represents 97 to 98 percent of all ART cycles performed in the United States.


Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review

Abstract: Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo- or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosis-associated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinum-resistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future.


Pivotal role of boron supplementation on bone health: A narrative review

Abstract:
BACKGROUND: Boron is a trace element that plays an important role in numerous biological functions, including calcium metabolism, growth and maintenance of bone tissue. However, there are still no precise indications regarding a possible role of boron supplementation, and its amount of supplementation, to maintain bone health. So the aim of this narrative review was to consider the state of the art on the effectiveness of boron supplementation (alone or with other micronutrients) on growth and maintenance of bone in humans through control of calcium, vitamin D and sex steroid hormone metabolism in order to suggest a daily dosage of boron supplementation.

MAIN FINDINGS: This review included 11 eligible studies: 7 regarding the supplementation with boron alone and 4 regarding supplementation with boron and other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (594) and the results are interesting.

CONCLUSIONS: The studies considered in this narrative review have evaluated the positive effectiveness on bone, in humans, through control of calcium, vitamin D and sex steroid hormone metabolism, considering a dietary supplementation of 3 mg/day of boron (alone or with other nutrients); this supplementation is demonstrably useful to support bone health (in order to prevent and maintain adequate bone mineral density), also considering the daily dose of 3 mg is much lower than the Upper Level indicated by EFSA in the daily dose of 10 mg.

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)


Regarding Surgical Management of Superficial Peritoneal Adolescent Endometriosis  by Laufer and Einarsson

Ken Sinervo

Center for Endometriosis Care, Atlanta, GA.

Journal of Pediatric and Adolescent Gynecology


Testing and interpreting measures of ovarian reserve: a committee opinion

Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org

Abstract: Ovarian reserve is defined as the number of oocytes remaining in the ovary, or oocyte quantity (oocyte number). Markers of ovarian reserve include hormone levels and sonographically measured features of the ovaries. These markers can be useful as predictors of oocyte yield following controlled ovarian stimulation and oocyte retrieval. However, they are poor predictors of reproductive potential independently from age. This document replaces the document of the same name last published in 2012 (Fertil Steril 2012;98:1407-15).


The role of endocrine-disrupting chemicals in uterine fibroid pathogenesis

Abstract:
PURPOSE OF REVIEW: Uterine leiomyoma (fibroids) is a gynecologic disorder impacting the majority of women in the United States. When symptomatic, these noncancerous tumors can cause severe morbidity including pelvic pain, menorrhagia, and infertility. Endocrine-disrupting chemicals (EDCs) may represent a modifiable risk factor. The aim of this review is to summarize recent human and experimental evidence on EDCs exposures and fibroids.

RECENT FINDINGS: Multiple EDCs are associated with fibroid outcomes and/or processes including phthalates, parabens, environmental phenols, alternate plasticizers, Diethylstilbestrol, organophosphate esters, and tributyltin. Epidemiologic studies suggest exposure to certain EDCs, such as di-(2-ethylhxyl)-phthalate (DEHP), are associated with increased fibroid risk and severity. Both human and experimental studies indicate that epigenetic processes may play an important role in linking EDCs to fibroid pathogenesis. In-vitro and in-vivo studies show that DEHP, bisphenol A, and diethylstilbestrol can impact biological pathways critical to fibroid pathogenesis.

SUMMARY: While research on EDCs and fibroids is still evolving, recent evidence suggests EDC exposures may contribute to fibroid risk and progression. Further research is needed to examine the impacts of EDC mixtures and to identify critical biological pathways and windows of exposure. These results could open the door to new prevention strategies for fibroids.

Current opinion in endocrinology, diabetes, and obesity


Myo-inositol supplementation to prevent gestational diabetes in overweight  non-obese women: bioelectrical impedance analysis, metabolic aspects, obstetric  and neonatal outcomes - a randomized and open-label, placebo-controlled clinical  trial

Rosario D'Anna

Department of Obstetrics and Gynecology, University of Messina, Italy.

Abstract: This study aims to evaluate the effects of myo-inositol supplementation on gestational diabetes mellitus (GDM) rates and body water distribution in overweight non-obese women. 223 overweight non-obese women pregnant were randomly assigned to the treatment group (2 g of myo-inositol plus 200 µg of folic acid) or to the placebo one (200 µg of folic acid). The treatment lasted until three weeks after delivery. A tetrapolar impedance analyser was used to study body composition. The incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group. There was a significant increase in TBW, ECW and ICW values in the placebo group compared to the myo-inositol group. We have recorded a significant reduction in the overall incidence of pregnancy-induced hypertension in the myo-inositol group compared with the placebo group. Our results demonstrate the effectiveness of myo-inositol supplementation in preventing GDM in overweight non-obese pregnant women.

International Journal of Food Sciences and Nutrition


Marital Satisfaction of Infertile Couples Using Natural Procreative Technology (NaProTECHNOLOGY)

Abstract: Infertility affects one in 16 married women in the United States where 12.7% of these seek treatment. The stress of infertility and treatment is known to impact marital satisfaction, which can be further complicated by personal and religious beliefs regarding the ethics of some assistive reproductive technologies. A morally acceptable approach to infertility diagnosis and treatment is natural procreative technology or NaProTECHNOLOGY (NPT) using the Creighton Model FertilityCare™ System. A quantitative, descriptive study utilizing demographic surveys and the Index of Marital Satisfaction found that couples using NPT reported marital satisfaction.

Journal of Christian Nursing : a Quarterly Publication of Nurses Christian  Fellowship


Is ART utilization the best indicator of access to fertility care?

Abstract:
While we agree with many of the points stated by Dyer et al. in their recent commentary inRBMO(Dyer et al., 2020), we believe their conclusions are focused too narrowly. Limiting the indicator of access to, and utilization of, fertility treatment to assisted reproductive technology (ART) excludes information that is of key importance for subfertile couples, populations, and policymakers. Even in countries where access to ART is widespread, there are more births in subfertile couples through non-ART treatment than through ART (Stanford et al., 2016).
While ART is necessary for some couples to have a child, it is not required for many subfertile couples, and overuse of ART may potentially be harmful (Annual Capri Workshop Group 2019). Focusing solely on ART as a metric may unnecessarily encourage overutilization (Boltz et al., 2017).
We believe the focus on ART and its outcomes for national and international registries of fertility treatment has stunted the scientific development of non-ART treatments, including those which seek to address underlying health conditions (Boyle et al., 2018). There is a pressing and critical need to develop robust registries of couples treated with non-ART treatments, for the improvement of outcomes and the promotion of robust consumer choice. (Spandorfer, 2020).
The ultimate measure of access to fertility care should be determined by the proportion of those with a desire for fertility who achieve a healthy live birth, whether or not ART is required to do so (Mascarenhas et al., 2012). Therefore, notwithstanding methodologic challenges, registry assessments should be developed and supported for all fertility treatments, not only ART.


Complications related to in vitro reproductive techniques support the implementation of natural procreative technologies

Roberto Angioli

Department of Obstetrics and Gynecology, University Campus Bio Medico, Rome, Italy. R.Angioli@unicampus.it.

Matteo Bertelli

MAGI EUREGIO, Bolzano, Italy; MAGI'S LAB, Rovereto (TN), Italy; EBTNA-LAB, Rovereto (TN), Italy. matteo.bertelli@assomagi.org.

Natale Capodicasa

Magi Balkans - Rare Genetic Diseases, Tirana, Albania. ncapodicasa@yahoo.it.

Marco Castori

Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. m.castori@operapadrepio.it.

Pietro Chiurazzi

Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli, Rome Italy. pietrosmile@yahoo.com.

Leonardo D'Agruma

Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. l.dagruma@operapadrepio.it.

Kalantary Rad Farshid

Surgical Department, Unit of Urology, Poliambulanza Foundation, Brescia, Italy. farshid.kalantaryrad@poliambulanza.it.

Ezio Fulcheri

UOSD Fetal and Perinatal Pathology, Department of Translational Research, Laboratory Medicine, Diagnostics and Services, IRCCS Giannina Gaslini Institute, Genoa, Italy. eziofulcheri@gaslini.org.

Aysha Karim Kiani

MAGI EUREGIO, Bolzano, Italy. ayshakiani@gmail.com.

Sandro Michelini

Department of Vascular Rehabilitation, San Giovanni Battista Hospital, Rome, Italy. s.michelini@acismom.it.

Angelantonio Notarangelo

Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. a.notarangelo@operapadrepio.it.

Paolo Petralia

General Director, IRCCS Giannina Gaslini Institute, Genoa, Italy. paolopetralia@gaslini.org.

Daniela Piccinelli

Department of Mother and Child Health, Unit of Obstetrics and Gynecology, Poliambulanza Foundation, Brescia, Italy. daniela.piccinelli@poliambulanza.it.

Francesco Plotti

Department of Obstetrics and Gynecology, University Campus Bio Medico, Rome, Italy. f.plotti@unicampus.it.

Pietro Scanzano

Director, San Giovanni Battista Hospital, Rome, Italy. p.scanzano@acismom.it.

Corrado Terranova

Department of Obstetrics and Gynecology, University Campus Bio Medico, Rome, Italy. C.Terranova@unicampus.it.

Gerolamo Tonini

Surgical Department, Unit of Urology, Poliambulanza Foundation, Brescia, Italy. gerolamotonini@libero.it.

Abstract:
BACKGROUND AND AIM: Infertility affects \~20% of the couples in the world. Assisted reproductive technologies (ARTs) are currently the most common treatment option for infertility. Nevertheless, ARTs may be associated with complications for mothers and/or offspring. Natural procreative technology (NaProTechnology) is a natural treatment which minimizes these risks by seeking to identify the causes of infertility to enable better treatments. This narrative review summarizes the complications related to ARTs and clarifies how the NaProTechnology approach can help ARTs to achieve better results or be used in alternative to ARTs.

METHODS: Data in the literature indicate that NaProTechnology is a natural approach for treating infertility.

RESULTS: The percentage of live births obtained by NaProTechnology is similar to that of ARTs.

CONCLUSIONS: An extensive search for the genetic defects causing infertility or subfertility through genetic testing can help both ARTs and NaProTechnology to achieve successful pregnancies. By discovering the underlying causes of infertility, genetic tests enable better family counseling, like the implications of transmitting risk- and disease-alleles to future generations.


Association between male infertility and male-specific malignancies: systematic review and meta-analysis of population-based retrospective cohort studies

Abstract:
OBJECTIVE: To investigate the current evidence that correlates impaired male fertility with the risk of developing male-related malignancies.

DESIGN: Systematic review and meta-analysis of population-based retrospective cohort studies.

SETTING: Not applicable.

PATIENT(S): Men diagnosed with impaired fertility status and subsequently observed to determine incidence risk in developing testicular cancer (TCa) or prostate cancer (PCa).

INTERVENTION(S): Not applicable.

MAIN OUTCOME MEASURE(S): Pooled risk ratio (RR) differences among male factor infertility subjects compared with a fertile control population, and meta-regression analysis according to age at baseline, mean follow-up, range of study time, and year of publication.

RESULT(S): Six studies met the inclusion criteria and were critically examined. Four studies examined male infertility and TCa (n = 161,634; 174 TCa cases), and four examined infertility in relation to PCa (n = 183,950 men; 377 PCa cases) from 1963 to 2014. The pooled RR was 2.033 (95% confidence interval [CI], 1.66-2.48); heterogeneity: Q = 3.04 (degree of freedom [df] = 3); I2 = 1.55% for TCa and 1.68 (95% CI, 1.17-2.4); Q = 23.3(df = 3); I2 = 87.1% for PCa.

CONCLUSION(S): Male infertility was associated with a subsequent risk of both TCa and PCa. Although the clinical significance of these findings remains uncertain, future studies should evaluate the underlying mechanisms to determine whether testis and prostate screening practices should be altered in men with male infertility.

CLINICAL TRIAL REGISTRATION NUMBER: PROSPERO 167277.


State of the Fertility Sector 2019/2020

State of the Fertility Sector 2019/2020

Abstract:
# State of the fertility sector 2019/2020
**Annual publication on our regulatory work**
Published: November 2020
[**Download the underlying data set as.xlsx (47KB)**](https://www.hfea.gov.uk/media/3289/state-of-the-sector-2019-20-underlying-data.xlsx)
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### About this report
We are the independent regulator of fertility treatment and human embryo research in the United Kingdom (UK). We aim to ensure that everyone who steps into a fertility clinic, and everyone born as a result of treatment, receives high quality care. We do this by licensing, monitoring and inspecting fertility clinics and providing free, clear and impartial information about fertility treatment, clinics, and egg, sperm and embryo donation.
State of the Sector is our annual report, which summarises what we have seen through our regulatory work during the year. The report is compiled from information gathered from our inspections throughout the year and uses other sources of information including our Register of fertility treatments, incident reports and patient feedback mechanisms.
In 2019/20, we introduced a [**Clinical Governance Quarterly Update**](https://portal.hfea.gov.uk/knowledge-base/clinic-focus/) which provides clinics with detailed insight into non-compliances in a more timely manner to help clinics improve compliance and prepare for inspections. As a result, the State of the Sector report this year provides a high-level overview of sector-wide compliance, reporting on the absolute number of inspections, non-compliances, incidents and complaints.
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### Impact of COVID-19 on the fertility sector
This report looks at the financial year 2019/20 (1 April 2019 – 31 March 2020), predominantly covering the period before any COVID-19 restrictions were put in place. As COVID-19 caused unprecedented demand on the NHS during the initial wave of the pandemic, the Human Fertilisation and Embryology Authority (HFEA) made the difficult decision to publish [**General Direction 0014**](https://po...


Restorative reproductive medicine for infertility and recurrent miscarriage in the outpatient gynaecological practice in Ukraine

O.V. Furman

National Pirogov Memorial Medical University, Vinnytsya

Abstract:
Objective: To assess the outcomes of treatment the couples with infertility or recurrent miscarriage with restorative reproductive approach and to identify predictors of success.

Methods: It was a retrospective study of 282 married couples, who were included in the program in 2 outpatient gynaecological centers in May 2010 - December 2014. The couples were observed to the end of pregnancy (or pregnancies) or withdrawal from the program. All the couples were taught to track the cycle with the Creighton Model FertilityCare System or the sympto-thermal method, and almost all received additional medical treatment. The main outcome was live birth, the secondary outcomes included conceptions, unsuccessful pregnancies, low birth weight and prematurity.

Results: In life-table analysis, the adjusted cumulative proportion of first conceptions for those completing up to 24 months of NPT treatment was 77.7% (crude proportion 47.9%). The adjusted cumulative proportion of live births was 73.6% (117 births, crude proportion 41.5%). Mean time to achieving pregnancy was 8 months. All the births except one were singleton. There were only 3 preterm births. The favorable predictors of live birth were younger age, shorter time of trying for baby, good compliance, pregnancy in history. The unfavorable were hyperprolactinemia, uterine fibroids, endometriosis, male factor.

Conclusion: The outcomes of restorative reproductive treatment the couples with infertility or recurrent miscarriage in Ukraine were comparable to those in Ireland and Canada.


Sperm DNA fragmentation testing: Summary evidence and clinical practice  recommendations

Robert Matthew Coward

University of North Carolina at Chapel Hill

Sandro C Esteves

Universidade Estadual de Campinas (UNICAMP)

Abstract: We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analytical information, clinical thresholds and interpretation of results. The remaining 28 recommendations relate to indications for sperm DNA fragmentation testing and clinical management. Clinical scenarios like varicocele, unexplained infertility, idiopathic infertility, recurrent pregnancy loss, intrauterine insemination, in vitro fertilisation/intracytoplasmic sperm injection, fertility counselling for men with infertility risk factors and sperm cryopreservation have been contemplated. The bulk evidence supporting the recommendations has increased in recent years, but it is still of moderate to low quality. This guideline provides clinicians with advice on best practices in sperm DNA fragmentation testing. Also, recommendations are provided on possible management strategies to overcome infertility related to sperm DNA fragmentation, based on the best available evidence. Lastly, we identified gaps in knowledge and opportunities for research and elaborated a list of recommendations to stimulate further investigation.


Current use of combined hormonal contraception is associated with glucose  metabolism disorders in perimenopausal women

Sirkka Keinänen-Kiukaanniemi

Center for Life Course Health Research, University of Oulu, Oulu, Finland.

Laure Morin-Papunen

Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, 90220 Oulu, Finland

Juha Tapanainen

Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland

Abstract:
Objective: The use of combined hormonal contraceptives (CHCs) worsens glucose tolerance, but the risk for glucose metabolism disorders remains controversial.
Design: The study is a prospective longitudinal population-based cohort study.

Methods: The study was based on a cohort population that comprised 1879 women born in 1966. At age 46, the women answered a questionnaire on contraceptive use and underwent an oral glucose tolerance test. Glucose metabolism indices were evaluated in current CHC (n = 153), progestin-only contraceptive (POC, n = 842), and non-hormonal contraceptive users (n = 884).

Results: In the entire study population, current CHC use was significantly associated with prediabetes (OR: 2.0, 95% CI: 1.3-3.2) and type 2 diabetes (OR: 3.3, 95% CI: 1.1-9.7) compared to non-hormonal contraceptive use. After 5 years of use, the prediabetes risk increased 2.2-fold (95% CI: 1.3-3.7) and type 2 diabetes risk increased 4.5-fold (95% CI: 1.5-13.5). Compared with the current POC use, current CHC use was significantly associated with prediabetes (OR: 1.9, 95% CI: 1.2-3.0). Current POC use was not associated with any glucose metabolism disorders. The results prevailed after adjusting for BMI and socioeconomic status.

Conclusions: CHC use in perimenopausal women was associated with a significantly increased risk of glucose metabolism disorders. This association should be considered in women with increased metabolic risk.


The Effects of Hormonal Contraceptives on the Brain: A Systematic Review of Neuroimaging Studies

Abstract: Background: Hormonal contraceptive drugs are being used by adult and adolescent women all over the world. Convergent evidence from animal research indicates that contraceptive substances can alter both structure and function of the brain, yet such effects are not part of the public discourse or clinical decision-making concerning these drugs. We thus conducted a systematic review of the neuroimaging literature to assess the current evidence of hormonal contraceptive influence on the human brain. Methods: The review was registered in PROSPERO and conducted in accordance with the PRISMA criteria for systematic reviews. Structural and functional neuroimaging studies concerning the use of hormonal contraceptives, indexed in Embase, PubMed and/or PsycINFO until February 2020 were included, following a comprehensive and systematic search based on predetermined selection criteria. Results: A total of 33 articles met the inclusion criteria. Ten of these were structural studies, while 23 were functional investigations. Only one study investigated effects on an adolescent sample. The quality of the articles varied as many had methodological challenges as well as partially unfounded theoretical claims. However, most of the included neuroimaging studies found functional and/or structural brain changes associated with the use of hormonal contraceptives. Conclusion: The included studies identified structural and functional changes in areas involved in affective and cognitive processing, such as the amygdala, hippocampus, prefrontal cortex and cingulate gyrus. However, only one study reported primary research on a purely adolescent sample. Thus, there is a need for further investigation of the implications of these findings, especially with regard to adolescent girls.


Oral contraceptive use and risk of suicidal behavior among young women

Abstract:
Background: Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association.

Methods: We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide.

Results: In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73-2.78 after 1 month of use, and 1.25-1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period.

Conclusions: Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.


Meeting Women's Requests for Intrauterine Device and Contraceptive Implant  Discontinuation: An Exploratory Survey of Physicians

Kasey Kajiwara

Department of Obstetrics Gynecology & Women's Health, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI (BK, ZK, KK, RS).

Amanda Williams

School of Education, University of Bristol, Bristol, United Kingdom (AM).

Abstract: Long acting reversible contraceptives (LARC), including intrauterine devices (IUDs) and contraceptive implants, can support an individual in meeting their reproductive goals by allowing them to prevent pregnancy effectively. These devices can also limit an individual's control over reproduction because they generally require an in-person visit to a health care provider for removal. Returning for another visit may be logistically challenging for many individuals who may need to arrange for transportation, childcare, or take time off from work. Effectively negotiating with a provider to request removal may be additionally challenging for medically underserved and disenfranchised people who may not feel empowered to do so. The objective of this study was to assess providers' willingness to honor patients' requests for IUD and contraceptive implant removal on the day of the request. A survey was conducted in which clinicians were presented with scenarios of women requesting IUD or implant removal. Clinicians were asked what they were most likely to do. A total of 105 clinicians were surveyed. The responses of 60 clinicians who inserted IUDs and 57 who provided the contraceptive implant were included in the analysis. When asked about same-day removal of an IUD or implant from a dissatisfied patient who requested removal, 40% stated they would remove the implant, and 57% stated they would remove the IUD on the day of the request. Findings from this study suggest many clinicians would be unwilling or unable to accommodate a patient's request for device removal at the time of their visit. This delay or refusal represents a significant barrier for patients and has implications for reproductive autonomy that should be further explored.

Hawai'i Journal of Health & Social Welfare


Supplementation of dehydroepiandrosterone (DHEA) in pre- and postmenopausal women  - position statement of expert panel of Polish Menopause and Andropause Society

Wojciech Zgliczyński

Postgraduate School of Molecular Medicine

Malgorzata Binkowska

Department of Gynecological Oncology and Obstetrics, Centre of Postgraduate Medical Education, Warsaw, Poland.

Abstract: Dehydroepiandrosterone (DHEA) concentration decreases with age, therefore, DHEA has been considered a hormone that reduces the symptoms associated with aging, so the usefulness of DHEA in premenopausal and postmenopausal women, and the options of hormone therapy have received a large amount of attention. The effectiveness of DHEA in the premenopausal women remains unclear, while in postmenopausal women with coexisting estrogens deficiency is controversial. Despite many years of study, the use of DHEA is still controversial, especially regarding its effectiveness. The aim of present article was to evaluate DHEA specific effects on metabolic parameters, bone mineral density, insulin resistance as well as the therapeutic potential of DHEA in preand postmenopausal women using measures of sexual activity, cognition and well-being. The summary of this article is the position statement of expert group of the Polish Menopause and Andropause Society regarding the efficacy and safety of DHEA supplementation in women. We concluded, that currently available clinical trials and meta-analyses indicate that DHEA supplementation is effective in women with adrenal insufficiency and chronically treated with exogenous glucocorticoids, postmenopausal women with low bone mineral density and/or osteoporosis, premenopausal women with sexual disorders and low libido, and in women with vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause. Currently available clinical trials also suggest that DHEA supplementation is probably effective in postmenopausal women with hypoactive sexual disorders, infertile women with diminished ovarian reserve, women suffering from depression and anxiety, and women with obesity and insulin resistance. No serious adverse effects have been reported.


The Case for Standardizing Cesarean Delivery Technique: Seeing the Forest for the  Trees

Abstract: In this Commentary, we explain the case for a standardized cesarean delivery surgical technique. There are three strong arguments for a standardized approach to cesarean delivery, the most common major abdominal surgery performed in the world. First, standardization within institutions improves safety, efficiency, and effectiveness in health care delivery. Second, surgical training among obstetrics and gynecology residents would become more consistent across hospitals and regions, and proficiency in performing cesarean delivery measurable. Finally, standardization would strengthen future trials of cesarean delivery technique by minimizing the potential for aspects of the surgery which are not being studied to bias results. Before 2013, more than 155 randomized controlled trials, meta-analyses or systematic reviews were published comparing various aspects of cesarean delivery surgical technique. Since 2013, an additional 216 similar studies have strengthened those recommendations and offered evidence to recommend additional cesarean delivery techniques. However, this amount of cesarean delivery technique data creates a forest for the trees problem, making it difficult for a clinician to synthesize this volume of data. In response to this difficulty, we propose a comprehensive, evidence-based and standardized approach to cesarean delivery technique.


Conception rates after fluoroscopy-guided fallopian tubal cannulation: an alternative to in vitro fertilization for patients with tubal occlusion

Abstract:
OBJECTIVE: Previous studies show good technical success rates for fallopian tube recanalization. Scarce literature exists regarding advance techniques currently used by interventional radiologists during fallopian tube recanalization procedures. This study investigates the level of intervention and tubal patency and its association with technical success and associated pregnancy outcomes.

METHODS: We retrospectively evaluated fallopian tube recanalization procedures performed at a single center in a 24-year period. A total of 160 couples undergoing a basic infertility evaluation were included. Hysterosalpingography with high pressure contrast injection followed by selective contrast, guidewire catheterization at the tubal ostium, and/or microcatheter/microwire recanalization were performed. Comparisons of the tubal fertilization rate by relevant characteristics were tested for statistical significance with t tests for continuous data or with Pearson chi-square tests for categorical data.

RESULTS: Technical success rate was 94% (319 of 341 tubes). High pressure contrast injection alone (184 of 341, 54%), selective catheterization (40%), and microcatheter/microwire (6%) interventions yielded technical success rates of 98%, 90%, and 73%, respectively. The overall rate of conception was 35% (17 of 48).

CONCLUSION: Current techniques of fallopian tube recanalization offer a desirable and safe option with high technical success for patients seeking treatment for infertility due to proximal fallopian tube obstruction.

Therapeutic Advances in Reproductive Health


Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review

Abstract:
OBJECTIVE: To consolidate evidence from systematic reviews and meta-analyses investigating the association between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease.

DESIGN: Umbrella review.

DATA SOURCES: Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31 August 2019.

REVIEW METHODS: Two independent reviewers undertook screening, data extraction, and quality appraisal. The population was women of reproductive age. Exposures were fertility related factors and adverse pregnancy outcomes. Outcome was cardiovascular diseases in women, including ischaemic heart disease, heart failure, peripheral arterial disease, and stroke.

RESULTS: 32 reviews were included, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three reviews were of moderate quality. A narrative evidence synthesis with forest plots and tabular presentations was performed. Associations for composite cardiovascular disease were: twofold for pre-eclampsia, stillbirth, and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes, and premature ovarian insufficiency; and less than 1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. A longer length of breastfeeding was associated with a reduced risk of cardiovascular disease. The associations for ischaemic heart disease were twofold or greater for pre-eclampsia, recurrent pre-eclampsia, gestational diabetes, and preterm birth; 1.5-1.9-fold for current use of combined oral contraceptives (oestrogen and progesterone), recurrent miscarriage, premature ovarian insufficiency, and early menopause; and less than 1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms. For stroke outcomes, the associations were twofold or more for current use of any oral contraceptive (combined oral contraceptives or progesterone only pill), pre-eclampsia, and recurrent pre-eclampsia; 1.5-1.9-fold for current use of combined oral contraceptives, gestational diabetes, and preterm birth; and less than 1.5-fold for polycystic ovary syndrome. The association for heart failure was fourfold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment.

CONCLUSIONS: From menarche to menopause, reproductive factors were associated with cardiovascular disease in women. In this review, presenting absolute numbers on the scale of the problem was not feasible; however, if these associations are causal, they could account for a large proportion of unexplained risk of cardiovascular disease in women, and the risk might be modifiable. Identifying reproductive risk factors at an early stage in the life of women might facilitate the initiation of strategies to modify potential risks. Policy makers should consider incorporating reproductive risk factors as part of the assessment of cardiovascular risk in clinical guidelines.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019120076.


Total oxidizable precursor assay in the determination of perfluoroalkyl acids in textiles collected from the United States

Abstract: Per- and polyfluoroalkyl substances (PFASs) are used in specialty/functional textiles to impart oil, water, and stain repellency. Little is known, however, with regard to the occurrence of PFASs in textiles including infant clothing. In this study, 13 perfluoroalkyl acids (PFAAs), comprising four perfluoroalkyl sulfonic acids (PFSAs; C4-C10) and nine perfluoroalkyl carboxylic acids (PFCAs; C4-C12) were determined in 160 textile samples collected from the United States. Two extraction methods, one involving a simple solvent extraction (i.e., before oxidation) and the other with an oxidative treatment (i.e., after oxidation) of textile extracts, were used. The sum concentrations of 13 PFAAs (i.e., ∑PFAA) in textile extracts before oxidation ranged from 2 (2 (14.2 ng/g). ∑PFAA concentrations were the highest in flame retarded textiles (n = 23; mean: 13.3 μg/m2; 59.4 ng/g), followed by water repellent textiles (n = 56; 2.88 μg/m2; 12.9 ng/g) and infant clothes (n = 81; 0.521 μg/m2; 2.33 ng/g). C4-C10 PFCAs accounted for at least three-quarters of the ∑PFAA content in our textile samples. Textile extracts analyzed after oxidative treatment exhibited ∑PFAA concentrations 10-fold higher than those in extracts analyzed prior to oxidation, which suggested that PFAA precursors are used in textiles. Precursors that generated C4-C5 PFCAs, upon oxidation, were more prevalent than those that yielded PFOA. The calculated dermal exposure doses in infants of PFAAs present in clothes were at least 1-2 orders of magnitude below the reference doses proposed by the United States Environmental Protection Agency. This is the first time that the oxidative treatment was applied in the analysis of PFASs in textiles, and our results suggest the existence of PFCA precursors in textiles.


The Effects of Menstrual Cycle Phase on Exercise Performance in Eumenorrheic Women: A Systematic Review and Meta-Analysis

Abstract:
BACKGROUND: Concentrations of endogenous sex hormones fluctuate across the menstrual cycle (MC), which could have implications for exercise performance in women. At present, data are conflicting, with no consensus on whether exercise performance is affected by MC phase.

OBJECTIVE: To determine the effects of the MC on exercise performance and provide evidence-based, practical, performance recommendations to eumenorrheic women.

METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases were searched for published experimental studies that investigated the effects of the MC on exercise performance, which included at least one outcome measure taken in two or more defined MC phases. All data were meta-analysed using multilevel models grounded in Bayesian principles. The initial meta-analysis pooled pairwise effect sizes comparing exercise performance during the early follicular phase with all other phases (late follicular, ovulation, early luteal, mid-luteal and late luteal) amalgamated. A more comprehensive analysis was then conducted, comparing exercise performance between all phases with direct and indirect pairwise effect sizes through a network meta-analysis. Results from the network meta-analysis were summarised by calculating the Surface Under the Cumulative Ranking curve (SUCRA). Study quality was assessed using a modified Downs and Black checklist and a strategy based on the recommendations of the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group.

RESULTS: Of the 78 included studies, data from 51 studies were eligible for inclusion in the initial pairwise meta-analysis. The three-level hierarchical model indicated a trivial effect for both endurance- and strength-based outcomes, with reduced exercise performance observed in the early follicular phase of the MC, based on the median pooled effect size (ES0.5 = - 0.06 [95% credible interval (CrI): - 0.16 to 0.04]). Seventy-three studies had enough data to be included in the network meta-analysis. The largest effect was identified between the early follicular and the late follicular phases of the MC (ES0.5 = - 0.14 [95% CrI: - 0.26 to - 0.03]). The lowest SUCRA value, which represents the likelihood that exercise performance is poor, or among the poorest, relative to other MC phases, was obtained for the early follicular phase (30%), with values for all other phases ranging between 53 and 55%. The quality of evidence for this review was classified as "low" (42%).

CONCLUSION: The results from this systematic review and meta-analysis indicate that exercise performance might be trivially reduced during the early follicular phase of the MC, compared to all other phases. Due to the trivial effect size, the large between-study variation and the number of poor-quality studies included in this review, general guidelines on exercise performance across the MC cannot be formed; rather, it is recommended that a personalised approach should be taken based on each individual's response to exercise performance across the MC.


Prevalence of Female Athlete Triad Risk Factors and Iron Supplementation Among High School Distance Runners: Results From a Triad Risk Screening Tool

Abstract:
BACKGROUND: Investigations of the female athlete triad (Triad) in high school athletes have found that 36% had low energy availability, 54% had menstrual abnormalities, and 16% had low bone mineral density (BMD). Limited data are available showing the prevalence of these risk factors in high school distance runners or regarding best practice on screening for the Triad in the adolescent population.

PURPOSE: To (1) evaluate the prevalence of Triad risk factors and iron supplementation in high school distance runners and (2) pilot a screening tool for Triad risk score.

STUDY DESIGN: Descriptive epidemiology study.

METHODS: The study population included female high school athletes who participated in cross-country/track. Participants completed a survey including questions regarding dietary habits, menstrual history, and bone stress injury (BSI) history. They then underwent evaluation of 25-hydroxyvitamin D, free triiodothyronine (T3), and dual-energy x-ray absorptiometry scan to measure body fat and BMD through use of age-, sex-, and ethnicity-matched Z scores. Triad scores were calculated. Relationships were analyzed using Spearman correlation coefficient.

RESULTS: There were 38 study participants (mean age, 16.9 years). Average body mass index was 19.8 kg/m2. Disordered eating or eating disorders were reported in 76.3% of runners; in addition, 23.7% reported delayed menarche, 45.9% had a history of amenorrhea or oligomenorrhea, 42.1% had low BMD (Z score < -1.0), and 15.8% reported prior BSI. Low free T3 was significantly associated with higher Triad risk scores (r S = -0.36; P = .028). More than 42% of athletes were supplementing iron.

CONCLUSION: The prevalence of Triad risk factors in high school distance runners was high. Free T3 was inversely associated with Triad score, which may serve as an indicator of low energy availability. Nearly half of the athletes were using iron supplementation.


Non-hormonal mediators of uterine fibroid growth

Abstract:
PURPOSE OF REVIEW: Uterine fibroids are the most common benign neoplasms of the female reproductive tract and one of the major public health concerns. Although most women with uterine fibroids are asymptomatic, over 30% of them will present with varying symptoms. This review focuses on the role of non-hormonal mediators and pathways in uterine fibroid biology. Furthermore, it provides data regarding the most recent findings in the field of compounds, which use those non-hormonal pathways in the medical therapy of uterine fibroids.

RECENT FINDINGS: Complex signaling pathway alterations are crucial for uterine fibroid development. The topic of the pathophysiology of uterine fibroids focuses mostly on steroids and other hormones. However, other very important pathways exist, and some of them are independent of hormones. Some of the most important pathways, which are non-hormonal, but in some cases still hormone-depended, include growth factors, cytokines and inflammation, Smad proteins, wingless type/β-catenin and others.

SUMMARY: Much more is known about hormonal than about non-hormonal signaling in uterine fibroids. Growth factors, early life exposure and inflammation are key factors in uterine fibroid biology. Numerous agents depend on those pathways and may find their place in the current and future therapy of uterine fibroids.

Current opinion in obstetrics & gynecology


Endometriosis and the Urinary Tract: From Diagnosis to Surgical Treatment

Abstract: We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools, including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team for complex cases that involve the urinary tract. While bladder deep endometriosis (DE) is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE, due to the serious health implications for women. When UTE exists, it is important to work within an interdisciplinary radiological and surgical team.


Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

Abstract:
AbstractObjectiveTo evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years).

Design: Prospective cohort study.

Setting: Nurses’ Health Study II (1993-2017).Participants79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years.

Main outcome measures: Hazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models.

Results: During 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers.

Conclusions: Irregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.


Sporadic anovulation is not an important determinant of becoming pregnant and  time to pregnancy among eumenorrheic women: A simulation study

Keewan Kim

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Background: Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilisation, and implantation. Anovulation is a first-line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability.

Objectives: To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles.

Methods: We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100 000 women based on data-driven probabilities of implantation, fertilisation, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, or daily. The model incorporated reductions in implantation and fertilisation rates for successive cycles of non-pregnancy.

Results: After 12 cycles, a reduction in the per cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7% vs 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; every other day or daily: 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, every other day: 88.8%; daily: 91.6%).

Conclusions: In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.


Differences in fracture prevalence and in bone mineral density between Chinese and White Canadians: the Canadian Multicentre Osteoporosis Study (CaMos)

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Angela M Cheung

Department of Medicine and Joint Department of Medical Imaging, Centre of Excellence in Skeletal Health Assessment, University Health NetworkUniversity of TorontoTorontoONCanada

Alexandra Papaioannou

McMaster University, Hamilton, ON, Canada

Abstract:
Fracture determinants differ between Canadians of Chinese and White descent, the former constituting the second largest visible minority group in Canada. The results of this study support the importance of characterizing bone health predictors in Canadians of different ethnicity to improve population-specific fracture prevention and treatment strategies.
Purpose: We aimed to compare clinical risk factors, bone mineral density, prevalence of osteoporosis, and fractures between Chinese and White Canadians to identify ethnicity-specific risks.

Methods: We studied 236 Chinese and 8945 White Canadians aged 25+ years from the Canadian Multicentre Osteoporosis Study (CaMos). The prevalence of osteoporosis using ethnicity-specific peak bone mass (PBM), and of prior and incident low trauma fractures were assessed and compared between groups. Linear regressions, adjusting for age and anthropometric measures, were used to examine the association between baseline and 5-year changes in BMD and ethnicity.

Results: Chinese participants had shorter stature, lower BMI, and lower rate of falls than White participants. Adjusted models showed no significant differences in baseline BMD between ethnic groups except in younger men where total hip BMD was 0.059 g/cm2 (0.009; 0.108) lower in Chinese. Adjusted 5-year BMD change at lumbar spine was higher in older Chinese women and men compared with Whites. When using Chinese-specific PBM, the prevalence of osteoporosis in Chinese women was 2-fold lower than when using that of White women The prevalence of fractures was higher in White women compared with Chinese with differences up to 14.5% (95% CI 9.2; 19.7) and 10.5% (95% CI 4.5-16.4) in older White men. Incident fractures were rare in young Chinese compared with White participants and not different in the older groups.

Conclusion: Our results support the importance of characterizing bone strength predictors in Chinese Canadians and the development of ethnicity-specific fracture prediction and prevention strategies.


The Baby-Friendly Hospital Initiative (BFHI): An Early Cross-Sectional Analysis of PRAMS Phase 8 Data on Hospital Practices and Breastfeeding Outcomes in Utah and Wyoming

Abstract:
Introduction: Breastfeeding has immediate and long-term benefits for both maternal and child health. This study examines the association between Baby-Friendly Hospital Initiative (BFHI) experiences and breastfeeding outcomes in the Mountain West region.

Methods: A cross-sectional (retrospective secondary data analysis) was performed using the 2016 Pregnancy Risk Assessment Monitoring System (PRAMS) data. The participants were derived from a stratified random sample of 2,013 women living in Utah and Wyoming who recently had a live birth and who were surveyed on BFHI practices. The association between BFHI experiences and breastfeeding duration were assessed using crude and adjusted Poisson regression models, controlling for other BHFI experiences and maternal age, pre-pregnancy BMI, household income, smoking, alcohol, delivery method, and number of days spent in the hospital post delivery.

Results: 82.4% and 82.3% of women from Utah and Wyoming, respectively, reported breastfeeding for 2 months or longer. After controlling for other BFHI experiences and potential confounders, the one shared BFHI experience that was associated with breastfeeding for 2 months or longer vs less than 2 months was starting breastfeeding in the hospital (adjusted prevalence ratio [aPR]=1.49, 95% CI (1.12, 1.98) in Utah and aPR=2.03, 95% CI (1.13, 3.64) in Wyoming. Among women in Utah and Wyoming, only 5 of 7 BFHI steps were significant for breastfeeding duration in at least one state.

Conclusion: There is substantial epidemiological support for health benefits to both mother and infant for exclusive breastfeeding to 6 months and prolonged breastfeeding until at least 1-year. Our findings suggest that women who initiate breastfeeding in the hospital may be more likely to breastfeed for a longer duration.


The association between preconception body mass index and subfertility among  Hispanic and non-Hispanic women: A cross-sectional study from Utah's Pregnancy  Risk Assessment Monitoring System survey (2012-2015)

Eric Ho Yin Lau

School of Public Health, The University of Hong Kong, Hong Kong, China

Rebekah H Ess

Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine.

Abstract:
Objective: To investigate the association between pre-pregnancy body mass index (BMI) and subfertility within a population-based cohort, exploring Hispanic ethnicity as a potential effect modifier.

Methods: We used cross-sectional study data from the Utah Pregnancy Risk Assessment Monitoring System from 2012-2015. Relationships between maternal pre-pregnancy BMI and subfertility were evaluated via Poisson regression models with robust error variance, accounting for the stratified survey sampling. Preconception BMI was analyzed continuously and categorically. Women's subfertility was defined via self-report in two ways: 1) time trying to achieve pregnancy; and 2) report of using fertility-related drugs/medical procedures.

Results: The median age was 27.0; 18.8% were obese, and 15.9% were Hispanic. Women with preconception obesity (BMI>30kg/m(2)), compared to normal weight women (18.4kg/ m(2)<BMI<25kg/m(2)) had a 1.85 (95% CI 1.43, 2.38) higher adjusted prevalence ratio (aPR) for having subfertility defined by time trying and a 1.73 (95% CI 1.20, 2.32) higher aPR for receiving fertility-enhancing drugs/medical procedures. Continuous models indicated a linear relationship between BMI and subfertility (aPR 1.04, 95% CI 1.03, 1.06 for time trying; and 1.06, 95% CI 1.03, 1.10 for receiving fertility-enhancing drugs/medical procedures).

Conclusions: Obese women, but not underweight or overweight women, reported higher subfertility than normal-weight women. Findings among this cohort of at-risk new mothers, oversampled on low education and birth weight and comprised of higher than the national average of Hispanics, indicated a dose-response relationship between obesity and subfertility.
Implications: Our findings highlight the importance of population-oriented obesity prevention for at-risk women with intentions to conceive.


Fecundability in relation to use of mobile computing apps to track the menstrual cycle

Elizabeth E Hatch

Department of Epidemiology Boston University School of Public Health Boston MA USA

Kenneth J Rothman

Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

Lauren A Wise

Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia

Abstract:
STUDY QUESTION: To what extent does the use of mobile computing apps to track the menstrual cycle and the fertile window influence fecundability among women trying to conceive?

SUMMARY ANSWER: After adjusting for potential confounders, use of any of several different apps was associated with increased fecundability ranging from 12% to 20% per cycle of attempt.

WHAT IS KNOWN ALREADY: Many women are using mobile computing apps to track their menstrual cycle and the fertile window, including while trying to conceive.

STUDY DESIGN, SIZE, DURATION: The Pregnancy Study Online (PRESTO) is a North American prospective internet-based cohort of women who are aged 21-45 years, trying to conceive and not using contraception or fertility treatment at baseline.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We restricted the analysis to 8363 women trying to conceive for no more than 6 months at baseline; the women were recruited from June 2013 through May 2019. Women completed questionnaires at baseline and every 2 months for up to 1 year. The main outcome was fecundability, i.e. the per-cycle probability of conception, which we assessed using self-reported data on time to pregnancy (confirmed by positive home pregnancy test) in menstrual cycles. On the baseline and follow-up questionnaires, women reported whether they used mobile computing apps to track their menstrual cycles ('cycle apps') and, if so, which one(s). We estimated fecundability ratios (FRs) for the use of cycle apps, adjusted for female age, race/ethnicity, prior pregnancy, BMI, income, current smoking, education, partner education, caffeine intake, use of hormonal contraceptives as the last method of contraception, hours of sleep per night, cycle regularity, use of prenatal supplements, marital status, intercourse frequency and history of subfertility. We also examined the impact of concurrent use of fertility indicators: basal body temperature, cervical fluid, cervix position and/or urine LH.

MAIN RESULTS AND THE ROLE OF CHANCE: Among 8363 women, 6077 (72.7%) were using one or more cycle apps at baseline. A total of 122 separate apps were reported by women. We designated five of these apps before analysis as more likely to be effective (Clue, Fertility Friend, Glow, Kindara, Ovia; hereafter referred to as 'selected apps'). The use of any app at baseline was associated with 20% increased fecundability, with little difference between selected apps versus other apps (selected apps FR (95% CI): 1.20 (1.13, 1.28); all other apps 1.21 (1.13, 1.30)). In time-varying analyses, cycle app use was associated with 12-15% increased fecundability (selected apps FR (95% CI): 1.12 (1.04, 1.21); all other apps 1.15 (1.07, 1.24)). When apps were used at baseline with one or more fertility indicators, there was higher fecundability than without fertility indicators (selected apps with indicators FR (95% CI): 1.23 (1.14, 1.34) versus without indicators 1.17 (1.05, 1.30); other apps with indicators 1.30 (1.19, 1.43) versus without indicators 1.16 (1.06, 1.27)). In time-varying analyses, results were similar when stratified by time trying at study entry (<3 vs. 3-6 cycles) or cycle regularity. For use of the selected apps, we observed higher fecundability among women with a history of subfertility: FR 1.33 (1.05-1.67).

LIMITATIONS, REASONS FOR CAUTION: Neither regularity nor intensity of app use was ascertained. The prospective time-varying assessment of app use was based on questionnaires completed every 2 months, which would not capture more frequent changes. Intercourse frequency was also reported retrospectively and we do not have data on timing of intercourse relative to the fertile window. Although we controlled for a wide range of covariates, we cannot exclude the possibility of residual confounding (e.g. choosing to use an app in this observational study may be a marker for unmeasured health habits promoting fecundability). Half of the women in the study received a free premium subscription for one of the apps (Fertility Friend), which may have increased the overall prevalence of app use in the time-varying analyses, but would not affect app use at baseline. Most women in the study were college educated, which may limit application of results to other populations.

WIDER IMPLICATIONS OF THE FINDINGS: Use of a cycle app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine LH), may increase fecundability (per-cycle pregnancy probability) by about 12-20% for couples trying to conceive. We did not find consistent evidence of improved fecundability resulting from use of one specific app over another.

STUDY FUNDING/COMPETING INTEREST(S): This research was supported by grants, R21HD072326 and R01HD086742, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. In the last 3 years, Dr L.A.W. has served as a fibroid consultant for AbbVie.com. Dr L.A.W. has also received in-kind donations from Sandstone Diagnostics, Swiss Precision Diagnostics, FertilityFriend.com and Kindara.com for primary data collection and participant incentives in the PRESTO cohort. Dr J.B.S. reports personal fees from Swiss Precision Diagnostics, outside the submitted work. The remaining authors have nothing to declare.

TRIAL REGISTRATION NUMBER: N/A.


Do fertility tracking applications offer women useful information about their  fertile window?

Abstract:
RESEARCH Question: To characterize mobile fertility tracking applications (apps) to determine the use of such apps for women trying to conceive by identifying the fertile window.
Design: An exploratory cross-sectional audit study was conducted of fertility tracking applications. Ninety out of a possible total 200 apps were included for full review. The main outcome measures were the underlying app method for predicting ovulation, the fertile window, or both, price to download and use the app, disclaimers and cautions, information and features provided and tracked, and app marketing strategies.
Results: All the apps except one monitored the women's menstrual cycle dates. Most apps only tracked menstrual cycle dates (n = 49 [54.4%]). The remainder tracked at least one fertility-based awareness method (basal body temperature, cervical mucus, LH) (n = 41 [45.6%]). Twenty-five apps measured dates, basal body temperature, LH and cervical mucus (27.8%). Seventy-six per cent of apps were free to download with free apps having more desirable features, tracking more measures and having more and better quality educational insights than paid apps. Seventy per cent of apps were classified as feminine apps, 41% of which were pink in colour.

Conclusions: Mobile fertility tracking apps are heterogenous in their underlying methods of predicting fertile days, the price to obtain full app functionality, and in content and design. Unreliable calendar apps remain the most commonly available fertility apps on the market. The unregulated nature of fertility apps is a concern that could be addressed by app regulating bodies. The possible benefit of using fertility apps to reduce time to pregnancy needs to be evaluated.


The Widespread Environmental Footprint of Indigo Denim Microfibers from Blue Jeans

Environmental Science & Technology Letters


Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate

Abstract: Adequate levels of folates are essential for homeostasis of the organism, prevention of congenital malformations, and the salvage of predisposed disease states. They depend on genetic predisposition, and therefore, a pharmacogenetic approach to individualized supplementation or therapeutic intervention is necessary for an optimal outcome. The role of folates in vital cell processes was investigated by translational pharmacogenetics employing lymphoblastoid cell lines (LCLs). Depriving cells of folates led to reversible S-phase arrest. Since 5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in the biosynthesis of an active folate form, we evaluated the relevance of polymorphisms in the MTHFR gene on intracellular levels of bioactive metabolite, the 5-methyltetrahydrofolate (5-Me-THF). LCLs (n = 35) were divided into low- and normal-MTHFR activity groups based on their genotype. They were cultured in the presence of folic acid (FA) or 5-Me-THF. Based on the cells' metabolic activity and intracellular 5-Me-THF levels, we conclude supplementation of FA is sufficient to maintain adequate folate level in the normal MTHFR activity group, while low MTHFR activity cells require 5-Me-THF to overcome the metabolic defects caused by polymorphisms in their MTHFR genes. This finding was supported by the determination of intracellular levels of 5-Me-THF in cell lysates by LC-MS/MS. FA supplementation resulted in a 2.5-fold increase in 5-Me-THF in cells with normal MTHFR activity, but there was no increase after FA supplementation in low MTHFR activity cells. However, when LCLs were exposed to 5-Me-THF, a 10-fold increase in intracellular levels of this metabolite was determined. These findings indicate that patients undergoing folate supplementation to counteract anti-folate therapies, or patients with increased folate demand, would benefit from pharmacogenetics-based therapy choices.


INVESTIGATING THE ROLE OF INFERTILITY IN ENDOMETRIOSIS RISK


Validity of the association between periodontitis and female infertility conditions: a concise review

Abstract: Hormones and inflammatory mechanisms are implicated with female reproductive function, including follicle maturation, ovulation, embryo implantation, and pregnancy. Periodontitis is a chronic inflammatory disease due to a polymicrobial disruption of the homeostasis and may be considered as a potential risk factor that affect female fertility. The role of periodontitis is becoming meaningful, with significant associations with polycystic ovary syndrome, endometriosis and bacterial vaginosis. Further, periodontitis is linked with known risk factors towards female infertility, such as age, obesity, and chronic kidney disease. This review aims to summarize the available evidence on the association between periodontitis and female infertility-associated conditions, and to discuss warranting steps in future research.


Chronic endometritis and reproductive failure: Role of syndecan-1

Yan-wen Xu

The First Affiliated Hospital, Sun Yat-sen University

Yuhua Li

Third Affiliated Hospital of Guangzhou Medical University

Li Ding

Tianjin Medical University General Hospital

Abstract: Chronic endometritis (CE) is an unusual inflammatory condition characterized by endometrial plasmacyte infiltration. It has a high prevalence in women with reproductive failure. Because of its characteristic localization patterns and molecular functions, syndecan-1 has been identified as a biomarker of plasmacyte, and syndecan-1 immunohistochemistry (IHC) becomes the most dependable diagnostic method for CE. In this review, we discuss the association between CE and reproductive failure, the clinicopathological characterization of CE, the function and expression of syndecan-1, the progress of syndecan-1 IHC in the diagnosis of CE, and the prediction of reproductive outcome.

American journal of reproductive immunology (New York, N.Y. : 1989)


The role of laparoscopy in paediatric and adolescent gynaecology

Abstract: Paediatric and adolescent gynaecology is a narrow field of medicine dealing with the diagnosis of and treatment of gynaecological diseases from the neonatal period to sexual maturity. The current trend in surgical gynaecology in the paediatric population is to minimise the degree of invasiveness of diagnostic and therapeutic procedures. This contributes to reducing the number of complications and the risk of infertility. Laparoscopic procedures are a challenge for paediatric surgeons and gynaecologists, not only because of the age of treated patients, and anatomical and physiological differences between different age groups but also because of the complexity of the pathology, the differentiation of cancer tumours, and the presence of congenital developmental defects.

Wideochirurgia i inne techniki maloinwazyjne = Videosurgery and other miniinvasive techniques


Creatine metabolism in the uterus: potential implications for reproductive biology

Abstract: Creatine is an amino acid derivative synthesized from arginine, glycine and methionine. It serves as the substrate for the creatine kinase system, which is vital for maintaining ATP levels in tissues with high and fluctuating energy demand. There exists evidence that the creatine kinase system operates in both the endometrial and myometrial layers of the uterus. While use and regulation of this system in the uterus are not well understood, it is likely to be important given uterine tissues undergo phases of increased energy demand during certain stages of the female reproductive cycle, pregnancy, and parturition. This review discusses known adaptations of creatine metabolism in the uterus during the reproductive cycle (both estrous and menstrual), pregnancy and parturition, highlighting possible links to fertility and the existing knowledge gaps. Specifically, we discuss the adaptations and regulation of uterine creatine metabolite levels, cell creatine transport, de novo creatine synthesis, and creatine kinase expression in the various layers and cell types of the uterus. Finally, we discuss the effects of dietary creatine on uterine metabolism. In summary, there is growing evidence that creatine metabolism is up-regulated in uterine tissues during phases where energy demand is increased. While it remains unclear how important these adaptations are in the maintenance of healthy uterine function, furthering our understanding of uterine creatine metabolism may uncover strategies to combat poor embryo implantation and failure to conceive, as well as enhancing uterine contractile performance during labor.