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.

Hysterectomy for the Transgendered Male: Review of Perioperative Considerations and Surgical Techniques with Description of a Novel 2-Port Laparoscopic Approach.

Transgendered individuals can suffer a significant amount of psychological distress that can be alleviated through hormonal treatments and/or gender-affirming surgery. The World Professional Association for Transgender Health considers a hysterectomy and bilateral salpingo-oophorectomy medically necessary gender-affirming procedures for the interested transgendered male. Several surgical approaches have been described in the literature, most of which endorse a laparoscopic approach. This review summarizes the available literature on surgical techniques in addition to reporting our institutional outcomes using a novel 2-port laparoscopic approach. Additional preoperative and perioperative considerations are needed when caring for this patient population and are reviewed.

Evolution of Knowledge, Awareness, and Practices regarding Zika Virus from 2016 to 2017.

Objective: Our team created a knowledge, attitudes, and practice (KAP) survey in order to assess changes over time in healthcare provider and community member awareness of Zika virus symptoms, transmission, treatment, and current and future concerns. Study Design: The cross-sectional survey was issued at an academic medical center in Washington, DC, and via an online link to healthcare providers and community members between June and August 2016. Survey distribution was then repeated the following year, from March to April 2017. Outcomes were compared by survey year and healthcare provider versus community member status using SAS Program Version 9.4. Results: Significant differences in knowledge, attitudes, and practices existed between 2016 and 2017 survey time points. By 2017, more respondents had knowledge of various Zika virus infection characteristics; however healthcare provider knowledge also waned in certain areas. Attitudes towards Zika virus infection displayed an overall decreased concern by 2017. Practice trends by 2017 demonstrated fewer travel restrictions to Zika-endemic areas and increased mosquito protective measures within the US. Conclusions: Our results provide novel insight into the transformation of knowledge, attitudes, and practice of community members and healthcare providers regarding Zika virus since its declaration as a public health emergency of international concern in 2016.

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.

Prior and novel coronaviruses, Coronavirus Disease 2019 (COVID-19), and human reproduction: what is known?

OBJECTIVE: To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. DESIGN: Review of English publications in PubMed and Embase to April 6, 2020. METHOD(S): Articles were screened for reports including coronavirus, reproduction, pathophysiology, and pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Reproductive outcomes, effects on gametes, pregnancy outcomes, and neonatal complications. RESULT(S): Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin-converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following Coronavirus Disease 2019 (COVID-19) infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-Coronavirus 2 (CoV-2) adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or Middle East respiratory syndrome (MERS), but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. Coronavirus Disease 2019 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. CONCLUSION(S): Coronavirus Disease 2019 infection may affect adversely some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.

Management of Bilateral Ectopic Pregnancies after Ovulation Induction Using Unilateral Salpingectomy and Methotrexate for the Remaining Ectopic with Subsequent Intrauterine Pregnancy.

Bilateral ectopic pregnancy is a rare phenomenon which is found with increased frequency when using assisted reproductive technology (ART). This diagnosis is most often made incidentally and intraoperatively, as ultrasound and serial ß-hCG trends have shown poor efficacy for accurate diagnosis. Management of bilateral ectopic pregnancies is most commonly reported using bilateral surgical removal of the ectopic pregnancy (salpingostomy and/or salpingectomy). We present a case of an ART patient with incidentally found bilateral tubal ectopic pregnancies, where multiple management strategies including medical and surgical techniques were used concurrently which resulted in a subsequent spontaneous intrauterine pregnancy. While the standard of care is difficult to establish, we recommend individualizing management decisions based on the patient's reproductive goals and overall risk profile.

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.