M.T. Connell

Timing luteal support in assisted reproductive technology: a systematic review.

OBJECTIVE To summarize the available published randomized controlled trial data regarding timing of P supplementation during the luteal phase of patients undergoing assisted reproductive technology (ART). DESIGN A systematic review. SETTING Not applicable. PATIENT(S) Undergoing IVF. INTERVENTION(S) Different starting times of P for luteal support. MAIN OUTCOME MEASURE(S) Clinical pregnancy (PR) and live birth rates. RESULT(S) Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed because of a high degree of clinical heterogeneity with regard to the timing, dose, and route of P. Two studies compared P initiated before oocyte retrieval versus the day of oocyte retrieval and PRs were 5%-12% higher when starting P on the day of oocyte retrieval. One study compared starting P on day 6 after retrieval versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing P start times on the day of oocyte retrieval versus 2 or 3 days after retrieval showed no significant differences in pregnancy. CONCLUSION(S) There appears to be a window for P start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. Although some studies have suggested a potential benefit in delaying vaginal P start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define P start time for luteal support after ART.

Intrauterine adhesion prevention after hysteroscopy: a systematic review and meta-analysis

BACKGROUND Despite years of studies evaluating prevention strategies for intrauterine adhesion formation after operative hysteroscopy, it is still unclear which strategies are most effective. OBJECTIVE The objective of the study was to perform a systematic review and meta-analysis to evaluate the effectiveness of postoperative prevention strategies on intrauterine adhesion formation following operative hysteroscopy. STUDY DESIGN Literature searches were conducted in MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases. Inclusion criteria were published randomized controlled clinical trials from 1989 to 2014 comparing any postoperative preventative measures of intrauterine adhesion after hysteroscopy. The main outcome measure was a reduction in postoperative intrauterine adhesion. Heterogeneity of the studies was evaluated using a Q test and an I(2) index. Analyses were performed using a random-effects model with outcome data reported as relative risk with 95% confidence interval. RESULTS Twelve studies were included in the systematic review. Eight studies compared similar treatment methods and were included in the meta-analysis. Three studies evaluated hyaluronic acid gel, of which 2 reported a significant decrease in intrauterine adhesion with treatment. The meta-analysis demonstrated a significant reduction of intrauterine adhesion when using hyaluronic acid gel. Two studies evaluated polyethylene oxide-sodium carboxymethylcellulose gel, 1 of which demonstrated a decrease in intrauterine adhesion with treatment. A meta-analysis showed a significant reduction of intrauterine adhesion with polyethylene oxide-sodium carboxymethyl cellulose gel. However, these 3 studies demonstrating a benefit of the gels in preventing adhesion formation were all conducted by the same research group. Other research groups have not confirmed these results. A sensitivity analysis excluding these trials from this single group demonstrated no benefit to adhesion prevention with either gel formation. Three studies investigated oral estrogen therapy after hysteroscopy and found no difference in intrauterine adhesion. A meta-analysis showed no decrease in intrauterine adhesion with estrogen therapy after hysteroscopy. Data were lacking to perform metaanalyses on the use of intrauterine balloon, intrauterine device, and other adhesion prevention barriers in preventing intrauterine adhesion. CONCLUSION There was a lack of definitive evidence to conclude that any treatment is effective in preventing posthysteroscopy uterine adhesion formation. The available literature has significant heterogeneity and a high risk of bias, making any definitive conclusions difficult.

Single vitrified blastocyst transfer maximizes liveborn children per embryo while minimizing preterm birth.

OBJECTIVE To compare live-birth rates, blastocyst to live-birth efficiency, gestational age, and birth weights in a large cohort of patients undergoing single versus double thawed blastocyst transfer. DESIGN Retrospective cohort study. SETTING Assisted reproduction technology (ART) practice. PATIENT(S) All autologous frozen blastocyst transfers (FBT) of one or two vitrified-warmed blastocysts from January 2009 through April 2012. INTERVENTION(S) Single or double FBT. MAIN OUTCOME MEASURE(S) Live birth, blastocyst to live-birth efficiency, preterm birth, low birth weight. RESULT(S) Only supernumerary blastocysts with good morphology (grade BB or better) were vitrified, and 1,696 FBTs were analyzed. No differences were observed in patient age, rate of embryo progression, or postthaw blastomere survival. Double FBT yielded a higher live birth per transfer, but 33% of births from double FBT were twins versus only 0.6% of single FBT. Double FBT was associated with statistically significant increases in preterm birth and low birth weight, the latter of which was statistically significant even when the analysis was limited to singletons. Of the blastocysts transferred via single FBT, 38% resulted in a liveborn child versus only 34% with double FBT. This suggests that two single FBTs would result in more liveborn children with significantly fewer preterm births when compared with double FBT. CONCLUSION(S) Single FBT greatly decreased multiple and preterm birth risk while providing excellent live-birth rates. Patients should be counseled that a greater overall number of live born children per couple can be expected when thawed blastocysts are transferred one at a time.

Elective single embryo transfer- the power of one

Despite the highest historical live birth success rates for couples undergoing in vitro fertilization (IVF), there has been an epidemic of iatrogenic twin and higher order gestation conceived from this treatment. Continued improvement in cryopreservation techniques have allowed preservation of supernumerary embryos for use in future cycles, and refinements in culture systems and embryo selection have resulted in the transfer of fewer embryos while maintaining favorable pregnancy rates. The voluntary transfer of a single high quality embryo, elective single embryo transfer (eSET), has significantly reduced multiple gestation rates and maximized the rate of singleton pregnancy without compromising overall success rates. Although eSET is the standard of care in several developed countries, utilization in the United States has been slow. States with mandated IVF insurance have seen decreases in preterm birth rates yielding down stream health care savings. Herein, the evolution and future applications of this practice to reduce the risk of iatrogenic twins is reviewed.

Preconception plasma phospholipid fatty acids and fecundability

Context Fatty acids (FAs) are important for reproductive processes, including steroidogenesis, though associations with fecundability, as measured by time to pregnancy (TTP), are unclear. Objective To investigate the relationship between preconception plasma phospholipid FA (PPFA) levels and time to human chorionic gonadotropin-pregnancy among women with prior pregnancy loss. Design, Setting, and Participants Prospective cohort of 1228 women attempting pregnancy (aged 18 to 40 years, with one or two prior pregnancy losses) followed for up to six cycles at four US university medical centers during 2006 to 2012. PPFA levels were measured at baseline. Main Outcome Measures Associations with fecundability overall and by body mass index (BMI) group after adjusting for confounders were estimated using fecundability odds ratios (FORs) and 95% CIs. False discovery rate (FDR) was used to account for multiple comparisons. Results Monounsaturated fatty acids (MUFAs) were associated with increased fecundability or shorter TTP [FOR, 1.08 (95% CI, 1.01 to 1.16) per unit increase in percentage of total FAs], whereas polyunsaturated fatty acids (PUFAs) were associated with decreased fecundability or longer TTP [FOR, 0.95 (95% CI, 0.91 to 1.00) per 1% change], though associations only remained significant after FDR adjustment among women with BMI <25 kg/m2. Saturated FA and trans FA were not associated with fecundability. Omega-3 FAs and omega-6 linoleic acid were not associated with fecundability. Conclusion We observed associations between preconception MUFA and PUFA levels and fecundability among women with normal BMI, highlighting the importance of FA composition among normal-weight women with prior pregnancy loss.

Vitamin D is Associated with Bioavailability of Androgens in Eumenorrheic Women with Prior Pregnancy Loss

Background Prior studies have reported mixed results regarding relationships between vitamin D, androgens, and sex hormone–binding globulin in patients with polycystic ovary syndrome. However, less is known regarding these associations in eumenorrheic, premenopausal women. Objective Our objective was to study the relationships between serum vitamin D and androgen biomarkers in eumenorrheic women with a history of pregnancy loss who were attempting pregnancy. Study Design This was an analysis of a cohort of 1191 participants from the Effects of Aspirin in Gestation and Reproduction trial (2006–2012). Participants were attempting to conceive, aged 18–40 years, with 1–2 documented prior pregnancy losses and no history of infertility, and recruited from 4 academic medical centers in the United States. Serum vitamin D (25‐hydroxyvitamin D) and hormone concentrations were measured at baseline. Results Vitamin D concentration was negatively associated with free androgen index (percentage change [95% confidence interval, –5% (–8% to –2%)] per 10 ng/mL increase) and positively associated with sex hormone–binding globulin (95% confidence interval, 4% [2–7%]), although not with total testosterone, free testosterone, or dehydroepiandrosterone sulfate after adjusting for age, body mass index, smoking status, race, income, education, physical activity, and season of blood draw. Conclusion Overall, vitamin D was associated with sex hormone–binding globulin and free androgen index in eumenorrheic women with prior pregnancy loss, suggesting that vitamin D may play a role in the bioavailability of androgens in eumenorrheic women. We are limited in making assessments regarding directionality, given the cross‐sectional nature of our study.

The Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial: A Story of Discovery

Abstract Human reproduction is an inefficient process. There are several drivers of complications along the path to and during pregnancy, one of which is inflammation. Treatments to mitigate the deleterious effects of aberrant inflammation with something inexpensive and widely available like aspirin could have dramatic global impact. The Effects of Aspirin in Gestation and Reproduction (EAGeR) trial enrolled women aged 18 to 40 years with one to two prior pregnancy losses and no diagnosis of infertility. Patients were randomized to either low‐dose aspirin or placebo. Here, we review the collective findings of the EAGeR trial to date and discuss several important lessons learned from the unique data resulting from this groundbreaking trial. Findings reported from this trial provide significant advances in the understanding of aspirins potential mechanisms in modulating reproductive processes and the role of inflammation in these processes. This review describes the collective findings of the EAGeR trial in the context of the existing literature regarding aspirin and inflammation in reproduction to inform relevant next steps in fertility and obstetric research, as well as potential implications for clinical care.

Recent advances in the development of transdermal delivery systems for treatment of infertility

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