Mitochondrial replacement therapy.

PURPOSE OF REVIEW: The present study briefly reviews the history of mitochondrial replacement therapy (MRT); however, the focus is on recent advancements and future directions of the field. Specifically addressing societal and legal concerns and advances in MRT. RECENT FINDINGS: There continue to be new ethical debates surrounding MRT. In addition, there have been advancements in MRT techniques which could improve potential outcomes. Furthermore, advances in genetics continue to provide alternative approaches to treatment of many diseases, including alternatives to MRT. SUMMARY: MRT may be beneficial to eradicate a severely debilitating and often fatal disease. Despite significant supporting safety and efficacy, there are still many social and legal barriers to instituting MRT to clinical practice.

Modern assessment of the uterine cavity and fallopian tubes in the era of high-efficacy assisted reproductive technology.

The high efficacy of modern assisted reproductive technology (ART) and increase in the number of noninfertile patients who are using ART for family building in the United States call into question the relevance of the standard, one-size-fits-all infertility evaluation. Here, we explore whether all patients presenting for ART need uterine cavity and tubal assessment and what tests are most appropriate, efficient, and cost-effective in current times.

Fertility preservation in transgender men and the need for uniform, comprehensive counseling.

Objective: To review the literature to assess best practices for counseling transgender men who desire gender-affirming surgery on fertility preservation options. Design: A scoping review of articles published through July 2021. Setting: None. Patients: Articles published in Cochrane, Web of Science, PubMed, Science Direct, SCOPUS, and Psychinfo. Interventions: None. Main Outcome Measures: Papers discussing transgender men, fertility preservation (FP), and FP counseling. Results: The primary search yielded 1,067 publications. After assessing eligibility and evaluating with a quality assessment tool, 25 articles remained, including 8 reviews, 5 surveys, 4 consensus studies, 3 retrospective studies, 3 committee opinions, and 2 guidelines. Publications highlighted the importance of including the following topics during counseling: (1) FP and family building options; (2) FP outcomes; (3) effects of testosterone therapy on fertility; (4) contraception counseling; (5) attitudes toward family building; (6) consequences of transgender parenting; and (7) barriers to success. Conclusions: Currently, there is a lack of standardization for comprehensive counseling about FP for transgender men. Standardized approaches can facilitate conversation between physicians and transgender men and ensure patients are making informed decisions regarding pelvic surgery and future family building plans.

Creating an Artificial 3-Dimensional Ovarian Follicle Culture System Using a Microfluidic System.

We hypothesized that the creation of a 3-dimensional ovarian follicle, with embedded granulosa and theca cells, would better mimic the environment necessary to support early oocytes, both structurally and hormonally. Using a microfluidic system with controlled flow rates, 3-dimensional two-layer (core and shell) capsules were created. The core consists of murine granulosa cells in 0.8 mg/mL collagen + 0.05% alginate, while the shell is composed of murine theca cells suspended in 2% alginate. Somatic cell viability tests and hormonal assessments (estradiol, progesterone, and androstenedione) were performed on days 1, 6, 13, 20, and 27. Confocal microscopy confirmed appropriate compartmentalization of fluorescently-labeled murine granulosa cells to the inner capsule and theca cells to the outer shell. Greater than 78% of cells present in capsules were alive up to 27 days after collection. Artificially constructed ovarian follicles exhibited intact endocrine function as evidenced by the production of estradiol, progesterone, and androstenedione. Oocytes from primary and early secondary follicles were successfully encapsulated, which maintained size and cellular compartmentalization. This novel microfluidic system successfully encapsulated oocytes from primary and secondary follicles, recapitulating the two-compartment system necessary for the development of the mammalian oocyte. Importantly, this microfluidic system can be easily adapted for sterile, high throughput applications.

Smith-Lemli-Opitz's Syndrome as a Possible Cause of Recurrent Pregnancy Loss: A Case Report.

Based on the known carrier frequency of Smith-Lemli-Opitz's syndrome (SLOS), the prevalence of this disease should be significantly higher than what is observed in the population. This may be due to a higher rate of pregnancy loss in affected embryos. Here, we present the case of a couple who underwent expanded carrier screening (ECS) after experiencing three first trimester pregnancy losses. Both parents were found to be carriers of SLOS mutations, and DNA analysis of the fetal remains of the third loss revealed the aborted fetus had inherited both the maternal and paternal mutations. This suggests SLOS as a reason for this patient's recurrent pregnancy loss (RPL), and therefore, ECS should be considered as part of the RPL work-up.

Beyond the "Jewish panel": the importance of offering expanded carrier screening to the Ashkenazi Jewish population.

OBJECTIVE: To assess whether or not the current American College of Obstetricians and Gynecologists (ACOG) recommendations regarding carrier screening are sufficiently robust in detecting mutations in the Ashkenazi Jewish (AJ) population. DESIGN: Cross-sectional study. SETTING: Outreach program at university community center. PATIENTS: Self-identified Jewish students, 18-24 years of age, interested in genetic carrier testing. INTERVENTIONS: Expanded carrier screening (ECS) with the use of a commercially available targeted genotyping panel including >700 mutations in 180 genes. MAIN OUTCOME MEASURES: Gene mutations found in this population were grouped into three categories based on ACOG's 2017 committee opinion regarding carrier screening: category 1: the four commonly recommended genetic conditions known to be a risk for this population; category 2: 14 genetic disorders that should be considered for more comprehensive screening, including those of category 1; and category 3: the ECS panel, which includes category 2. RESULTS: A total of 81 students underwent screening and 36 (44.4%) were ascertained to be carriers of at least one mutation. A total of 45 mutations were identified, as 8 students were carriers for more than one condition. If testing were limited to category 1, 84% of the mutations would not have been identified, and if limited to category 2, 55% of mutations would have gone undetected. CONCLUSIONS: Individuals of Ashkenazi Jewish descent are at significant risk for carrying a variety of single-gene mutations and therefore they should be offered panethnic ECS to increase the likelihood of detecting preventable disorders.

Efficacy of progestin-only treatment for the management of menopausal symptoms: a systematic review.

IMPORTANCE: Menopause is associated with bothersome symptoms for many women, including mood changes, hot flushes, sleep problems, and fatigue. Progesterone is commonly prescribed in combination with estrogen therapy. Although monotherapy with progestins has been used as treatment of menopausal symptoms in women with contraindications to estrogens, the optimal route, and dosage of progestin monotherapy has not been established. OBJECTIVE: To assess whether progestin as a standalone treatment is effective for treating vasomotor and mood symptoms associated with menopause. EVIDENCE REVIEW: We conducted a systematic review using PubMed and Embase databases from January 1980 to January 2020. We included randomized controlled trials (RCTs) that investigated different forms of progestin for the treatment of vasomotor or mood symptoms associated with menopause. FINDINGS: A systematic search of 892 studies identified seven RCTs involving a total of 601 patients. The available literature was heterogeneous in terms of formulation and dose of progesterone; administration ranged from 5 to 60 mg of transdermal progesterone, 10 to 20 mg oral medroxyprogesterone acetate, and 300 mg of oral micronized progesterone. Duration of treatment also differed between studies, ranging from 21 days to 12 months (median: 12 wks). Three of seven RCTs reported that progestin therapy led to an improvement of vasomotor symptoms (VMS) in postmenopausal women. The largest study administering oral progestin using 300 mg micronized progesterone reported a 58.9% improvement in VMS (vs 23.5% in placebo group, n = 133), whereas the largest study using transdermal progesterone reported no improvement (n = 230). No study reported an improvement of mood symptoms. Side effects, such as headaches and vaginal bleeding, were significant in five of seven RCTs and led to discontinuation of treatment in 6% to 21% of patients. CONCLUSIONS AND RELEVANCE: A beneficial effect was reported in some trials with the transdermal route at longer duration and with oral treatment at higher doses for VMS for progesterone-only therapy. This report may help to inform future studies of progestin-only therapy for the treatment of menopausal symptoms.

Video Summary:http://links.lww.com/MENO/A671.

Gynecologic cancer screening in the transgender male population and its current challenges.

As the transgender community gains visibility and recognition, healthcare disparities have become more apparent. Reports estimate that 1-1.5 million people belong to this community in the United States. Despite efforts to become more inclusive, access to healthcare is challenging in a system built on a binary model that exacerbates gender dysphoria and on healthcare insurance schemes that do not cover gender affirmation therapy. Another large challenge is the paucity of scientific and medical knowledge when it comes to caring for the transgender community. More research to build knowledge is necessary to provide evidence-based quality care. In an attempt to bring guidance for gynecologic and breast cancer screening for the transgender male population, we conducted a review of the literature published in PubMed. Here, we present a review of the challenges, as well as guidelines for breast, uterus, and cervix screening for the transgender male population.