Vanquishing multiple pregnancy in in vitro fertilization in the United States-a 25-year endeavor.

The practice of in vitro fertilization has changed tremendously since the birth of the first in vitro fertilization infant in 1978. With the success of early in vitro fertilization programs in the United States, there was a substantial rise in twin births nationwide. In the mid-1990s, more than 30% of in vitro fertilization cycles resulted in twin or higher-order multifetal pregnancies. Since that time, we not only have witnessed improvements in laboratory and treatment efficacy but also have seen a dramatic impact on pregnancy outcomes, specifically regarding twin pregnancies. Because the field evolved and the risks of multifetal pregnancies became more salient, in 2019, the rate of twin pregnancies had dropped to <7% of cycles. This improvement was largely because of technical advancements and revised professional guidance: culturing embryos longer before transfer, improved freezing technology, embryo preimplantation genetic testing, and revised professional guidance regarding the number of embryos to transfer. These developments have led to single-embryo transfer becoming the standard of care in most scenarios. We used national in vitro fertilization surveillance data of all autologous in vitro fertilization cycles from 1996 to 2019 to illustrate trends in the following improved outcomes: autologous embryo transfer cycles involving blastocyst-stage embryos, vitrified embryos, preimplantation genetic testing cycles, total number of embryos being transferred per cycle, and single-embryo transfer usage over time. Among deliveries from autologous embryo transfers, we highlighted trends in singleton births over time and proportion of deliveries involving twins, triplets, quadruplets, or greater. The notable progress in reducing the rate of multifetal pregnancies with in vitro fertilization was largely attributed to a series of technical and clinical actions, culminating in an 80% reduction in the incidence of multiple births without a loss in overall treatment effectiveness.

A multinational study of acute and long-term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT.

Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (GALT), documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L.

A Case-Control Study of Follicular Fluid Cytokine Profiles in Women with Diminished Ovarian Reserve.

Ovarian reserve is an important determinant of a woman's reproductive potential, and women with diminished ovarian reserve (DOR) often seek in vitro fertilization (IVF). The underlying etiology of DOR is unknown, but follicular fluid cytokine concentrations likely play a role in follicular development and maturation. The present study seeks to investigate the expression of cytokines in follicular fluid (FF) of women with DOR undergoing IVF and explore correlated functional pathways. One hundred ninety-four women undergoing ovarian stimulation were recruited at the time of oocyte retrieval. Women were classified as having DOR if they met one or more of the following criteria: AMH < 1 ng/ml, FSH > 10 mIU/ml, and/or AFC < 10. Controls included women undergoing IVF for male factor, tubal factor due to tubal ligation, or planned oocyte cryopreservation (non-oncologic). The concentrations of 480 cytokines and related growth factors in follicular fluid were determined using a multiplex immunoassay. Fifty-nine cytokines had significantly different concentrations (53 higher and 6 lower) in the DOR relative to the control group after adjusting for age and body mass index (BMI) (false discovery rate; FDR < 0.1). Using the most informative 44 biomarkers as indicated by a random forest (RF) model, an area under the curve (AUC) of 0.78 was obtained. Thus, follicular microenvironment differs between women with DOR and normal ovarian reserve. The differentially expressed cytokines belong to diverse processes that are primarily involved in follicular maturation and ovulation. These changes may play an important role in treatment outcomes in women with DOR.

National egg-freezing trends: cycle and patient characteristics with a focus on race/ethnicity.

OBJECTIVE: To describe the trends and characteristics of oocyte cryopreservation (OC) cycles stratified by self-reported race/ethnicity in the United States DESIGN: Retrospective cohort analysis using the Society for Assisted Reproductive Technology Clinical Outcome Reporting System SETTING: US fertility clinics PATIENTS: All patients undergoing OC from 2012 through 2016 INTERVENTIONS: None MAIN OUTCOME MEASURES: The OC cycle trends were analyzed on the basis of race/ethnicity: non-Hispanic white, non-Hispanic black, Asian/Pacific islander, Hispanic, and other (American Indian, Alaskan native, or mixed race). RESULTS: Between 2012 and 2016, there was a total of 29,631 OC cycles; the total number of cycles increased yearly from 2,925 in 2012 to 8,828 in 2016. When compared with the demographics of the United States, OC was underused by some minority patient groups because majority of the cycles (66.5%) were performed in white patients. The total number of OC cycles increased annually among all the ethnic groups, most notably among Asian patients. The patients of all the ethnic backgrounds were most commonly under 35 years of age and underwent 1 OC cycle, except for Asian patients, who most frequently underwent OC between the ages of 35 and 37 years and were more likely to have undergone ≥2 cycles than patients of other minority groups. After adjustment for cofounders, there were no clinically significant differences in oocyte yield and the percentage of maturation across the racial/ethnic groups. CONCLUSIONS: Nationally, OC cycles have been increasing in number, most often in patients under the age of 35 years, with similar proportions of patients of minority groups pursuing OC over time. The oocyte yield was comparable across the ethnic groups. Future research regarding subsequent thawing outcomes is warranted.

Tranexamic Acid for Prevention and Treatment of Postpartum Hemorrhage: An Update on Management and Clinical Outcomes.

IMPORTANCE: Postpartum hemorrhage (PPH) remains a major cause of maternal mortality worldwide, occurring in both vaginal and cesarean deliveries. We have witnessed improvements in both prevention and treatment of PPH. Tranexamic acid (TXA) has been investigated as a potential adjunct therapy to uterotonics within this setting. OBJECTIVE: The aim of this article is to summarize existing recommendations on the use of TXA in obstetrics and review current data on clinical outcomes after TXA use. EVIDENCE ACQUISITION: We reviewed guidelines from a number of professional societies and performed an extensive literature search reviewing relevant and current data in this area. RESULTS AND CONCLUSIONS: In the prevention of PPH, TXA use before both vaginal and cesarean deliveries reduces the amount of postpartum blood loss and should be considered in patients at higher risk for hemorrhage. In the treatment of PPH, TXA should be initiated early for maximal survival benefit from hemorrhage, and it provides no additional benefit if administered more than 3 hours from delivery. Overall, current evidence assessing the risks of TXA use in an obstetric population is reassuring.