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To determine the ongoing pregnancy rate among patients with infertility with a low antimüllerian (AMH) level compared with those with a normal AMH level after oral and injectable ovulation induction (OI)/intrauterine insemination (IUI).Retrospective cohort.Academic center.Patients completing ≥1 medicated OI/IUI cycle at our center between 2015 and 2019 were included. The AMH levels were measured within 12 months of treatment initiation. The cohort was stratified into low AMH (AMH level,1.0 ng/mL) and normal AMH (AMH level, ≥1.0 ng/mL) groups. All subsequent medicated OI/IUI cycles occurring within 1 year of initial cycle start date were included up to the third completed cycle or until an ongoing pregnancy was recorded. Patients were stratified by age (35, 35-40, and40 years), and the relationship between the low and normal AMH groups and each binary endpoint were quantified as risk ratios using the age-adjusted Poisson models.None.Ongoing pregnancy.A total of 3,122 patients completed 5,539 oral antiestrogen cycles, and 1,060 completed 1,630 injectable gonadotropin cycles. For oral antiestrogen treatment, pregnancy outcomes, including ongoing pregnancy rate per cycle, for patients with a low AMH level were comparable with those for patients with a normal AMH level (35 years, 15.4% vs. 14.9%; 35-40 years, 10.0% vs. 11.0%; and40 years, 2.8% vs. 3.3%). For injectable gonadotropin treatment, the ongoing pregnancy rate was lower in the low AMH group than in the normal AMH group for the ages of35 (12.1% vs. 23.5%; relative risk [RR], 0.52 [95% confidence interval {CI}, 0.28-0.97]) and 35-40 (12.5% vs. 18.5%; RR, 0.70 [95% CI, 0.49-0.99]) years but comparable with that for patients aged40 years (3.0% vs. 4.0%; RR, 0.86 [95% CI, 0.31-2.35]). The proportion of multifetal gestations was similar between the low and normal AMH groups treated with oral antiestrogens (13.1% vs. 10.8%); however, for injectable gonadotropin treatment, patients with a normal AMH level had a higher proportion of multifetal gestations (18.6% vs. 31.1%).Compared with normal ovarian reserve, treatment with oral antiestrogens for OI/IUI for patients with low ovarian reserve results in comparable follicular development and ongoing pregnancy rates for all age groups. When patients with low ovarian reserve are treated with gonadotropins for OI/IUI, multifollicular recruitment is less likely resulting in a significantly decreased ongoing pregnancy rate for patients aged35 and 35-40 years but also a decrease in multifetal gestations. Overall, the ongoing pregnancy rates of 8.7% per oral antiestrogen cycle and 8.1% per injectable gonadotropin cycle in patients with low ovarian reserve are comparable with the expected rates in the general infertility population.

What is the impact of advancing paternal age, stratifying for maternal age, on fresh embryo transfer cycle outcomes?All first autologous fresh embryo transfer cycles between 2013 and 2019 at a single high-volume academic institution were retrospectively reviewed. Female age was dichotomized along the cohort median of (37 years) (Female-Young [F-Y]:37 years; Female-Old [F-O]: ≥37 years). Male age was stratified along the cohort median (38 years) and 90th centile (48 years) (Male-Young [M-Y]:38 years; Male-Intermediate [M-I]: ≤38 and48 years; Male-Old [M-O]: ≥48 years). The primary outcome of interest was the odds of live birth using logistic regression. Secondary outcomes included odds of implantation, clinical intrauterine pregnancy and pregnancy loss. All models were adjusted for continuous female age, use of surgically retrieved testicular spermatozoa, severe oligozoospermia and cleavage- versus blastocyst-stage embryo transfer.A total of 6704 couples were included and were divided into six groups based on paternal/maternal age groups (F-Y/M-Y: 2288; F-Y/M-I: 750; F-Y/M-O: 97; F-O/M-Y: 679; F-O/M-I: 2310; F-O/M-O: 580). While some associations were seen on univariable logistic regression, none of the groups with increasing paternal age showed any statistically significant differences on multivariable logistic regression with respect to implantation, clinical intrauterine pregnancy, pregnancy loss or live birth.Advanced paternal age does not impact clinical outcomes in fresh transfer cycles. The authors postulate that IVF with or without intracytoplasmic sperm injection is able to overcome the deleterious effects of advancing paternal age on sperm quality and subsequent embryo performance.

Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (Seq) in the SNEDDS (superSNEDDS, 250% of Seq). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of Seq), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% Seq in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48 h to 1 month under ambient conditions. The PK study in rats displayed significantly higher Cmax and AUC0-7h (3-fold increase) and faster Tmax for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.

What is the blastocyst conversion rate in embryo cryopreservation cycles, per year of female age?Retrospective cohort study including patients undergoing their first ovarian stimulation cycle at our center with planned freeze-all strategy January 1st, 2014-June 30th, 2020. Primary outcome was blastocyst conversion rate. Secondary outcomes included mature oocyte and fertilization rates. Patients were stratified by year of age to assess oocyte yield and embryo development outcomes.3,362 patients were included. The median blastocyst conversion rate in patients ≤30 was 66.7% (interquartile range 50.0-86.6) and remained statistically comparable through age 40 with a significant decline among ages ≥41 (41-years: marginal effect (ME) -5.2% (-9.7 to -0.7); 42-years: ME -9.6% (-14.3 to -4.8); 43-years: ME -7.7% (-12.8 to -2.6); ≥44-years: ME -20.8% (-26.5 to -15.1)). For the entire cohort, the median mature oocyte rate was 81.8% and the median fertilization rate was 81.8%. The mature oocyte and fertilization rates remained statistically comparable for each year of age except age ≥44 which had a statistically significantly increased mature oocyte rate (ME 4.4% (1.3 to 7.5)) and statistically significantly decreased fertilization rate (ME -5.8% (-9.8 to -1.9)) CONCLUSIONS: In embryo cryopreservation cycles, the blastocyst conversion rate remained statistically comparable through age 40 followed by a statistically significant decline for patients ≥41; however, the mature oocyte and fertilization rates were not impacted by increasing age until age ≥44. Even in women ≥44, over 40% of fertilized oocytes developed to blastocyst. Overall, this information is useful when counseling patients during the embryo culture stage regarding predicted blastocyst yield.

Background Obstructed Mullerian anomalies in adolescents can be grouped into complete outflow obstruction or unilateral outflow obstruction. The challenge with unilateral obstructions is that diagnosis can be delayed for weeks to years, as menstruation occurs normally through the patent side and thus obstruction is often not initially considered in the differential diagnosis. Cases In this case series, we present 3 unusual and challenging cases of unilateral Mullerian obstructions in adolescent female patients, along with strategies for diagnosis and management. Each case involves a unique variation of a recognized Mullerian anomaly that was initially misdiagnosed, leading to a significant delay in definitive diagnosis and treatment. Summary and Conclusion These cases highlight that even among the well-described Mullerian anomalies, there can be unusual variations. Patients who do not respond to initial management or who develop new symptoms should be further evaluated to confirm the correct diagnosis Tools that may be helpful in making the correct diagnosis include imaging studies that use contrast dye to better delineate cavities and their connections, magnetic resonance imaging with a radiologist experienced in Mullerian anomalies, and an examination under anesthesia. A definitive diagnosis is critical to the successful management of these conditions, and individualized management plans are required for each patient depending on their specific anomaly and their preferences for treatment.

Do women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF?A retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P0.05 was considered to be statistically significant.A total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24-28 weeks (5.5 versus 1.0%, P = 0.021).Minority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

Objective To describe the incidence of first trimester clinical pregnancy loss in the infertile population during the first wave of the COVID-19 pandemic in New York City. Design Web-based cross-sectional survey. Setting New York City-based academic reproductive medicine practice. Patient(s) A total of 305 infertile patients with a confirmed intrauterine pregnancy in their first trimester between December 1, 2019, and April 1, 2020, were matched by age and treatment type to pregnant patients from the year prior. Intervention(s) None. Main Outcome Measure(s) First trimester clinical pregnancy loss rate. Result(s) In total, the first trimester pregnancy loss rate was lower in the COVID-19 era cohort compared with that in the pre-COVID-19 era cohort (11.9% vs. 20.1%). There was no difference between cohorts in the pregnancy loss rate of women conceiving via fresh embryo transfer (19.6% vs. 24.4%) or via frozen embryo transfer with preimplantation genetic testing (5.4% vs. 9.5%,). In women conceiving via frozen embryo transfer without preimplantation genetic testing, the pregnancy loss rate was statistically lower in the COVID-19 group (12.5% vs. 24.5%). There was no difference in the pregnancy loss rate by treatment type when stratifying by COVID-19 testing or symptom status. Of the 40 (13.1%) patients with a pregnancy loss, there was no difference in self-reported COVID-19 symptoms or symptom type compared with results in those who did not experience a pregnancy loss. Conclusion Despite patients expressing significant worry about COVID-19 and pregnancy, our data provides reassuring information that the first trimester pregnancy loss rate is not elevated for women conceiving via assisted reproductive technology during the global COVID-19 pandemic.

Objective To determine if the time from oocyte retrieval to frozen embryo transfer (FET) in the natural cycle affects reproductive or neonatal outcomes. Design Retrospective cohort. Setting Not applicable. Patient(s) Five hundred and seventy-six consecutive freeze-all cycles from January 2011 to December 2018 followed by natural cycle FET of a single blastocyst. Intervention(s) None. Main Outcome Measure(s) Primary outcome of live birth; secondary outcomes of preterm delivery (24–37 weeks) and small for gestational age (SGA) with a multivariable logistic regression performed with adjustment for age, infertility diagnosis, ovulatory trigger type, and preimplantation genetic testing (PGT). Result(s) Before adjustment for confounding, we found a statistically significantly different live-birth rate (57.7% vs. 48.6%) for natural cycle FET occurring in the first versus second menstrual cycle, respectively. In a multivariate analysis, performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle did not statistically significantly impact the odds of live-birth rate. After adjustment for age, diagnosis, and ovulatory trigger type, only PGT was associated with statistically significantly increased odds of live birth compared with no PGT. There were no differences in the incidence of SGA (male, 6.6% vs. 2.3%; female, 9.8% vs. 11.1%) or preterm delivery (1.6% vs. 5.6%) between both groups. Conclusion(s) Performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle after ovarian stimulation did not statistically significantly impact the odds of live birth or neonatal outcomes.

What is the impact of low body mass index (BMI) on live birth rates and obstetric outcomes in infertile women treated with IVF and fresh embryo transfer?This was a retrospective cohort study of infertile patients in an academic hospital setting who underwent their first oocyte retrieval with planned autologous fresh embryo transfer between 1 January 2012 and 31 December 2018. The primary study outcome was live birth rate. Secondary outcomes were IVF treatment and delivery outcomes. Underweight patients were stratified into a significantly underweight group (body mass index [BMI]17.5 kg/mA total of 5229 patients were included (significantly underweight, 76; mildly underweight, 231; normal weight, 4922), resulting in 4798 embryo transfers. After oocyte retrieval, there were no significant differences between groups for total oocytes, mature oocyte yield and number of supernumerary blastocysts cryopreserved. Among women who had an embryo transfer, there were no significant differences in the live birth rates in significantly (31.0%, odds ratio [OR] 0.67, confidence interval [0.95, CI] 0.40-1.13) and mildly (37.7%, OR 0.95, CI 0.73-1.33) underweight patients compared with normal-weight patients (35.9%). Additionally, there were no statistically significant increased risks of preterm delivery, Caesarean delivery or a low birthweight (2500 g) neonate.Mildly and significantly underweight infertile women have similar pregnancy and live birth rates to normal-weight patients after IVF treatment. In addition, underweight patients do not have an increased risk of preterm delivery (37 weeks), Caesarean delivery or a low birthweight neonate.