An audit of the obstetric outcome of 148 consecutive pregnancies from assisted conception: implications for neonatal services

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial

Schisterman EF et al., 2020 · JAMA · Free full text on PubMed Central

Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth. To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth.Design, setting, and participantsThe Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019. Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months.Main outcomes and measuresThe co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, -0.9% [95% CI, -4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]). Conclusions and relevanceAmong a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility. ClinicalTrials.gov Identifier: NCT01857310.

Caffeinated Beverage Intake and Serum Caffeine Metabolites and Risk of Pregnancy Loss (OR17-04-19)

Purdue-Smithe A et al., 2019 · Current Developments in Nutrition

Preconception Vitamin D Status and Offspring Sex Ratio Among Women with Prior Pregnancy Loss (OR17-05-19)

Purdue‐Smithe A et al., 2019 · Current Developments in Nutrition · Free full text on PubMed Central

Caffeinated beverage intake and serum caffeine metabolites and risk of pregnancy loss

Purdue‐Smithe A et al., 2019 · Current Developments in Nutrition

The association between caffeine and pregnancy loss remains controversial due to limitations of prior studies such as relying on self-reported intake only, exposure measurement after clinical confirmation of pregnancy, and potential time-varying confounding by nausea/vomiting and lifestyle factors, which may be affected by prior caffeine exposure. Thus, our aim was to evaluate associations of preconception and early pregnancy serum caffeine, paraxanthine, and theobromine, self-reported intake of caffeinated beverages, and risk of pregnancy loss among 1228 reproductive-age women attempting pregnancy in the EAGeR trial during 2007–2011. We estimated HRs and 95% CIs for any pregnancy loss, hCG loss (prior to ultrasound confirmation), and clinical loss (after ultrasound confirmation) according to caffeinated beverage intake and caffeine biomarkers measured at preconception and the 8(th) week of gestation using weighted adjusted Cox proportional hazards models. At preconception, 67%, 28%, and 9% of women reported any intake of caffeinated sodas, coffee, and tea, respectively. Preconception total caffeinated beverage intake of ≥3 vs. 0 cups/day was associated with 85% (95% CI: 1.18, 2.94) higher risk of any pregnancy loss, driven primarily by associations for hCG loss (HR: 2.88 (95% CI: 1.20, 6.91)). Caffeinated soda intake was associated with hCG loss (≥2 vs. 0.2 vs. ≤0.2 ng/mL) at preconception was strongly associated with hCG loss (HR: 4.51 (95% CI: 1.36, 14.91)). Serum caffeine, paraxanthine, and theobromine measured at the 8th week of gestation were not associated with risk of loss. Collectively, these data suggest that caffeine intake prior to pregnancy may increase risk of pregnancy loss, particularly in early gestation. Funding Sources: Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD.

The effect of fertility drugs and in vitro methods on the outcome of 106 triplet pregnancies

Lipitz S et al., 1993 · Fertil Steril

To compare the effect of fertility drugs and IVF on the outcome of triplet pregnancies. Prospective clinical study. A single university medical center. One hundred six consecutive triplet pregnancies treated from 1984 through 1992. The frequency of pregnancy loss, livebirths, and antenatal and neonatal complications was compared in spontaneous, clomiphene citrate (CC), menotropins, and IVF triplet pregnancies. Eighty-one of the 106 (76.4%) triplet pregnancies progressed beyond 25 weeks, comprising 6 of 7 (85.7%) spontaneous pregnancies, 13 of 16 (81.2%) CC induced, 44 of 56 (78.6%) menotropin induced, and 18 of 27 (66.6%) IVF gestations. There were no significant differences in the stillbirth and neonatal mortality rates according to the mode of conception. The mean gestational ages and the mean birth weights were similar in the four groups. The frequency of premature contractions, premature rupture of membranes, cesarean section, and neonatal complications were similar in the ovulation induction and IVF pregnancies. Triplet pregnancies after ovulation induction and IVF have a similar outcome.

Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies

Tan SL et al., 1992 · Am J Obstet Gynecol

To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.

Outcomes from assisted reproductive technology

Van Voorhis BJ, 2006 · Obstetrics and gynecology

The use of assisted reproductive technology (ART) for treating the infertile couple is increasing in the United States. The purpose of this paper is to review the short-term outcomes after ART. Pregnancy rates after ART have shown nearly continuous improvement in the years since its inception. A number of factors affect the pregnancy rate, with the most important being a woman's age. Certain clinical diagnoses are associated with a poorer outcome from ART, including the presence of hydrosalpinges, uterine leiomyomata that distort the endometrial cavity, and decreased ovarian reserve. Multiple gestations are the major complication after ART. New laboratory techniques, including extended embryo culture, may allow the transfer of fewer embryos to maintain pregnancy rates while reducing the risk of multiple gestations. Although much of the morbidity in children born after ART is the result of multiples, recent analysis suggests that even singletons are at higher risk for perinatal morbidity, including preterm delivery and small for gestational age infants. In vitro fertilization may be associated with a slight increased risk for birth defects. The major short-term complication of ART in women is the development of ovarian hyperstimulation syndrome. This syndrome is difficult to predict, but new treatments are being developed that may limit its frequency. Because of its high pregnancy rate, couples are moving to ART more quickly in the management of their infertility. All outcomes of ART, including pregnancy rates and adverse complications, need to be compared with standard non-ART therapy when deciding the appropriate course of treatment for a given couple.

Neonatal outcome of spontaneous and assisted twin pregnancies

Zuppa AA et al., 2001 · Eur J Obstet Gynecol Reprod Biol

Over the last 10 years, diffusion of assisted reproduction techniques (ovarian stimulation, IVF, GIFT) has led to an increased incidence of multiple pregnancies and consequently, of the related obstetric-neonatal problems. In this study, multiple births have been studied, with particular reference to the twin births occurring in the Gemelli hospital, Rome. The hospital is also a reference centre for obstetric pathologies and infertility treatment. In particular, attention has been focused on neonatal outcome, comparing twins born from spontaneous and assisted pregnancies. 228 neonates from spontaneous twin pregnancies and 32 from assisted twin pregnancies were taken into consideration with regard to: premature birth, low birth-weight, intrauterine growth retardation, weight discordance, Apgar score, major neonatal diseases, and mortality. Results showed a significant higher incidence of prematurity and low birth-weight, as well as a significant lower gestational age, occurring more frequently in twins resulting from assisted pregnancies than in twins from spontaneous pregnancies. Furthermore, the incidence of severe depression at birth and respiratory disease was significantly higher in twins from assisted pregnancies than in those from spontaneous pregnancies, despite similar gestational age and birth-weight.