Fine-tuning the dose of recombinant human follicle-stimulating hormone alfa to individualize treatment in ovulation induction and ovarian stimulation cycles: a real-world database analysis.

Introduction: Fine-tuning of injectable gonadotropin doses during ovulation induction (OI) or ovarian stimulation (OS) treatment cycles with the aim of using doses low enough to minimize the risk of excessive ovarian response while maintaining optimal efficacy may be facilitated by using an adjustable-dose pen injector. We examined the incidence and magnitude of individualized gonadotropin dose adjustments made during cycles of OI or OS, followed by either timed intercourse or intrauterine insemination, with or without oral medications, and assessed the relationship between patient characteristics and dosing changes using real-world evidence. Methods: This was an observational, retrospective cohort study using electronic medical records from a large US database of fertility centers. Data from patients who had undergone a first recombinant human follicle stimulating hormone alfa (r-hFSH-alfa/follitropin alfa) treated OI/OS cycle followed by timed intercourse or intrauterine insemination between 2015 and 2016 were included. Percentages of OI/OS cycles involving r-hFSH-alfa dose adjustments (in increments of ±12.5 IU or greater) with or without oral medications (clomiphene citrate or letrozole) were analyzed. Results: Of 2,832 OI/OS cycles involving r-hFSH-alfa administration, 74.6% included combination treatment with orals; 25.4% involved r-hFSH-alfa alone. As expected, the starting dose of r-hFSH-alfa was lower for cycles that used r-hFSH-alfa with orals than r-hFSH-alfa only cycles (mean [SD]: 74.2 [39.31] vs 139.3 [115.10] IU). Dose changes occurred in 13.7% of r-hFSH-alfa with orals versus 43.9% of r-hFSH-alfa only cycles. Dose adjustment magnitudes ranged from ±12.5 IU to ±450 IU. The smallest adjustment magnitudes (±12.5 IU and ±25 IU) were used frequently and more often for dose increases than for dose decreases. For r-hFSH-alfa with orals and r-hFSH-alfa only cycles, the smallest adjustments were used in 53.5% and 64.5% of cycles with dose increases and in 35.7% and 46.8% of cycles with dose decreases, respectively. Discussion: In OI/OS cycles followed by timed intercourse or intrauterine insemination, r-hFSH-alfa dose adjustments were frequent. In cycles that included orals, r-hFSH-alfa starting doses were lower and dose changes were fewer than with r-hFSH-alfa alone. Smaller dose adjustments facilitate individualized treatment with the goal of reducing the risks of multiple gestation, cycle cancellation, and ovarian hyperstimulation syndrome.

Follicle flushing does not improve live birth and increases procedure time: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing ART using autologous gametes. INTERVENTION(S): A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020. MAIN OUTCOME MEASURE(S): Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes. RESULT(S): Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant. CONCLUSION(S): Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.

Polycystic Ovarian Syndrome: Impact on Adult and Fetal Health.

Women with the polycystic ovarian syndrome (PCOS) may have an increased risk for complications in pregnancy including miscarriage, gestational diabetes mellitus, hypertensive disorders of pregnancy, higher rates of cesarean delivery, and abnormalities in fetal growth. In addition, PCOS has been associated with the development of type II diabetes mellitus, hypertension, cardiovascular disease, obstructive sleep apnea, endometrial cancer, depression and anxiety, and nonalcoholic fatty liver disease. In understanding that PCOS is a disease impacting more than just a woman's fertility, prevention and early identification of risk factors for affiliated conditions is essential.

COVID-19 in pregnancy.

Evidence continues to emerge on the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) in pregnancy. Compared with previous coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome), recent reports suggest that pregnant women who contract SARS-CoV-2 have lower rates of maternal and fetal complications; however, the incidence of preterm birth remains elevated. The potential for vertical transmission is still under investigation. Universal testing of women admitted to labor and delivery is being encouraged in most centers.

Fertility Preservation Before Deployment: Oocyte and Sperm Freezing in Members of the Active Duty Military.

Active duty military service and deployment has the potential to compromise fertility through combat-related genitourinary injury, gonadotoxic exposures, and physical separation from a partner. Despite a growing interest among the military community as well as promising efficacy and safety data, fertility preservation remains an uncovered benefit for active duty soldiers. In 2016, the Pentagon proposed a program that would cover oocyte and sperm cryopreservation for any member of the active duty military desiring its use. Regrettably, that funding was not secured and predeployment fertility preservation remains an out-of-pocket expense. Today, advocacy groups, non-for-profit organizations, and physicians remain vigilant in their attempts to drive another government initiative through Congress. While activism continues, it is important to stress the value of fertility preservation counseling in soldiers' predeployment preparation and military family planning.

Evaluating the Utility of Intralipid Infusion to Improve Live Birth Rates in Patients with Recurrent Pregnancy Loss or Recurrent Implantation Failure.

CONTEXT: Intralipid is used to improve clinical outcomes in patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF) with elevated natural killer (NK) cells. Data supporting this practice is conflicting but suggestive of minimal benefit. AIMS: The aims of this study are to determine if intralipid infusion improves live birth rates and if is a cost-effective therapy in the RPL/RIF population. SETTINGS AND DESIGN: This was a large REI private practice, retrospective cohort study. SUBJECTS AND METHODS: Charts of 127 patients who received intralipid from 2012 to 2015 were reviewed and compared to historical control data. T-tests and Chi-square analyses evaluated demographics and cycle statistics. Chi-square analyses assessed impact on clinical pregnancy and live birth rates. Cost analysis was performed from societal perspective with a one-way sensitivity analysis. RESULTS: Patients with live births were noted to have a higher average number of previous live births and were more likely to have had a frozen embryo transfer in the intralipid cycle in comparison to those with unsuccessful pregnancy outcomes. Neither clinical pregnancy nor live birth rates were significantly improved from baseline rates quoted in the literature (P = 0.12 and 0.80, respectively). Intralipid increased costs by $681 per live birth. If live birth rates were >40% using intralipid and <51% without intervention, neither strategy was favored. CONCLUSIONS: Intralipid does not improve live birth rates and is not cost-effective for patients with RIF or RPL and elevated NK cells. This study supports the growing literature demonstrating the minimal benefit of screening for and treating elevated peripheral NK cells.

Assisted Reproductive Technology and Epigenetics.

Assisted reproductive technology (ART) is responsible for 1.7% of births in the United States annually. Despite a large number of studies promoting the efficacy and safety of these practices, there have been reports of imprinting disorders occurring at higher frequencies in children born through ART. Driven by findings in animal studies, it has been postulated that various ART procedures employed at critical points in embryonic development may predispose the genomic imprinting process to errors. Alterations in DNA methylation patterns at imprinting control centers have been reported by some studies to occur more frequently in children with imprinting disorders conceived by ART compared with spontaneous conception, though these findings are not consistently demonstrated and controversy has surrounded the strength of these associations. The rarity of imprinting disorders with a reliance of studies on disease registry cohorts, wide variations in ART protocols, and a lack of proper control groups limit the ability to substantiate associations between imprinting disorders and ART. Large, prospective cohort studies with a focus on molecular etiologies of these conditions are needed to discern whether a true association exists. Based on current evidence, the absolute risk of imprinting disorders after ART is low and screening for imprinting disorders in children conceived by ART is not warranted.

Isolated Absent Thelarche in a Patient With Neurofibromatosis Type 1 and Acromegaly.

BACKGROUND: Isolated absent thelarche is a rare condition that is infrequently reviewed in the literature. CASE: A 28-year-old woman with neurofibromatosis type 1 and acromegaly presented with absent breast development despite hormone therapy. Examination noted a normally developed woman with acromegalic features and Tanner stage I breasts. Hormone studies and karyotype were normal. Magnetic resonance imaging of the patient's brain demonstrated a voluminous pituitary. Chromosome microarray analysis diagnosed the neurofibromatosis 1 microdeletion syndrome. Breast ultrasonography and surgical consultation were offered. CONCLUSIONS: Neither neurofibromatosis type 1, acromegaly, nor neurofibromatosis 1 microdeletion syndrome are linked to absent thelarche. After attempting hormone therapy, patients with absent thelarche should be evaluated for congenital breast anomalies, estrogen receptor abnormalities, or gene defects. Psychological and surgical consultation should also be offered.