Elevated body mass index in modified natural cycle frozen euploid embryo transfers is not associated with live birth rate.

PURPOSE: To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos. METHODS: This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m2) category: normal weight (18.5-24.9), overweight (25-29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes. RESULTS: 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4% normal weight, 61.2% overweight, and 64.2% obese). There was also no difference for the secondary outcome, CPR, across all categories (58.5%, 65.5%, and 66.7%, respectively). This was confirmed in GEE analysis when adjusting for confounders. CONCLUSION: While increased weight has commonly been implicated in poor pregnancy outcomes, the effect of BMI on the success of mNC-FET remains debated. Across five years of data from a single institution using euploid embryos in mNC-FET cycles, elevated BMI was not associated with reduced LBR or CPR.

Pregnancy and neonatal outcomes of letrozole versus natural cycle frozen embryo transfer of autologous euploid blastocyst.

PURPOSE: To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET). METHODS: Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5 mg of daily letrozole for 5 days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness. RESULTS: The demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7 days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38 weeks and 1 day for LTZ; 39 weeks and 0 day for NC) were full term. CONCLUSION: There were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6 days does not appear to be clinically significant, this warrants larger studies.

The impact of euploid blastocyst morphology and maternal age on pregnancy and neonatal outcomes in natural cycle frozen embryo transfers.

PURPOSE: To evaluate whether morphology impacts the pregnancy and neonatal outcomes of euploid blastocysts, and whether maternal age still affects outcomes when top-graded, euploid blastocysts are used. METHODS: This retrospective cohort study included all natural-cycle frozen embryo transfers (NC-FET) using an autologous, euploid blastocyst from June 2016 to June 2020 (n = 610). There were five groups based on embryo grade: AA, AB, BA, BB, and "any C". For analysis of only AA-graded embryos, there were three maternal age groups: < 35, 35-39, and 40 + years. The main outcomes measured were clinical pregnancy and live birth rates, while the secondary outcomes included neonatal outcomes such as gestational age at delivery and birthweight. Multivariable logistic regression models were performed to adjust for confounders. RESULTS: Euploid blastocysts with poorer morphology had lower odds of pregnancy and live birth; specifically, embryos with inner cell mass (ICM) graded as "C" had statistically significant decreased odds of pregnancy (aOR 0.33, p = 0.04) and live birth (aOR 0.32, p = 0.03) compared with ICM grade "A". The differences in pregnancy rate between trophectoderm grades were not statistically significant. Even in cycles that transferred a top-graded (AA) euploid embryo, maternal age at transfer was independently associated with outcomes. Embryo grade and maternal age, however, did not significantly impact neonatal outcomes such as prematurity and birthweight. CONCLUSION: The morphology of euploid blastocysts and maternal age at NC-FET both independently impact pregnancy outcomes. Neonatal outcomes were similar across embryo morphology and maternal age groups, suggesting that lower morphology euploid embryos not be discounted as viable options for transfer.

Withholding antibiotics does not reduce clinical pregnancy outcomes of natural cycle frozen embryo transfers.

OBJECTIVE: To assess the impact of withholding doxycycline on the success rate of natural cycle frozen embryo transfers (NC-FET). DESIGN: Retrospective cohort study. SETTING: Single academic institution. PATIENT(S): Women undergoing 250 NC-FET with euploid blastocysts performed by a single provider. INTERVENTION(S): One hundred and twenty-five NC-FET cycles performed after January 2019 without antibiotic administration compared with 125 NC-FET cycles before January 2019 with doxycycline administration. MAIN OUTCOME MEASURE(S): Primary outcome: live birth (LB) or ongoing pregnancy rate (OPR, defined as pregnancies ≥13 weeks); secondary outcomes included positive ß-human chorionic gonadotropin (ß-hCG) level and clinical pregnancy rate (CPR, defined as the presence of fetal cardiac activity on ultrasound). RESULT(S): Each group of women comprised 125 NC-FET during the study period of March 2017 to March 2020. The women's mean age was 36.3 years and mean body mass index was 24 kg/m2. Between the two groups, the baseline characteristics were similar, including age, body mass index, race, smoking status, parity, endometrial thickness, Society of Assisted Reproductive Technology diagnosis, and number of prior failed transfers. Comparing NC-FET with doxycycline administration versus without, we found no statistically significant difference in LB-OPR (64% vs. 62.6%), positive ß-hCG (72.8% vs. 74.0%), or CPR (68% vs. 65.9%). After controlling for all variables in a logistic regression, doxycycline still had no effect on LB-OPR. CONCLUSION(S): In this analysis of similar patients undergoing NC-FET by a single provider, withholding doxycycline does not reduce success rates. Given the risks of antibiotics, our findings support withholding their use in NC-FET.

Pregnancy success rates for lesbian women undergoing intrauterine insemination.

OBJECTIVE: To compare the pregnancy outcomes of lesbian women undergoing donor sperm intrauterine insemination (IUI) with that of heterosexual women undergoing IUI using partner or donor sperm. DESIGN: Retrospective cohort analysis. SETTING: Two academic fertility practices. PATIENTS: All IUI cycles between 2007 and 2016. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary outcomes included clinical pregnancy (CP) rates and live birth/ongoing pregnancy (LB) rates. The baseline characteristics and cycle characteristics were compared between the two groups using absolute standardized differences (ASDs). To account for the correlation between cycles per patient, a generalized estimating equation method for multivariable logistic regression was used. RESULTS: A total of 11,870 IUI cycles were included, of which 393 were in lesbian women using donor sperm and 11,477 were in heterosexual women with infertility using either partner or donor sperm. The CP rates were similar between the lesbian and heterosexual groups (13.2% vs. 11.1%, respectively, ASD = 0.06). In addition, the LB rates were similar between the two groups (10.4% vs. 8.3%, respectively, ASD = 0.10). After implementing the generalized estimating equation in a multivariable logistic regression, the lesbian group had an overall higher odds of CP (adjusted odds ratio 1.40, 95% confidence interval: [1.04-1.88]) and LB (adjusted odds ratio 1.59, 95% confidence interval [1.15-2.20]) compared with the heterosexual group. The clinical miscarriage rate was higher in the heterosexual group compared with that in the lesbian group (23.8% vs. 15.4%, respectively, ASD = 0.21). CONCLUSION: Although the unadjusted rates were similar between the two groups, the adjusted CP and LB odds were significantly higher for lesbian women undergoing IUI for procreative management than those for heterosexual women undergoing IUI for infertility.