Approximately 0.5–1.4% of natal males and 0.2–0.3% of natal females meet DSM-5 criteria for gender dysphoria, with many of these individuals self-describing as transgender men or women. Despite recent improvements both in social acceptance of transgender individuals as well as access to gender affirming therapy, progress in both areas has been hampered by poor understanding of the etiology of gender dysphoria. Prior studies have suggested a genetic contribution to gender dysphoria, but previously proposed candidate genes have not yet been verified in follow-up investigation. In this study, we expand on the topic of gender identity genomics by identifying rare variants in genes associated with sexually dimorphic brain development and exploring how they could contribute to gender dysphoria. To accomplish this, we performed whole exome sequencing on the genomic DNA of 13 transgender males and 17 transgender females. Whole exome sequencing revealed 120,582 genetic variants. After filtering, 441 variants in 421 genes remained for further consideration, including 21 nonsense, 28 frameshift, 13 splice-region, and 225 missense variants. Of these, 21 variants in 19 genes were found to have associations with previously described estrogen receptor activated pathways of sexually dimorphic brain development. These variants were confirmed by Sanger Sequencing. Our findings suggest a new avenue for investigation of genes involved in estrogen signaling pathways related to sexually dimorphic brain development and their relationship to gender dysphoria.

Objective To report cases of in vitro fertilization-frozen embryo transfer (IVF-FET) with single blastocyst transfer resulting in di-or tri-chorionic pregnancies, and to review the literature on monozygotic, multi-chorionic pregnancies originating at the blastocyst stage. Design Retrospective case series and literature review. Materials and methods All in vitro fertilization cycles (fresh, frozen, autologous, and donor oocyte) performed between June 2012 and June 2017 at the University of California, San Francisco Center for Reproductive Health, were reviewed retrospectively. Cycles with cleavage-stage embryos or transfer of more than one blastocyst were excluded. Cycles were analyzed to determine if clinical pregnancy occurred with the presence of two or more gestational sacs noted on initial ultrasound. An indepth chart review was performed with further exclusions applied that would lend credence to dizygosity rather than monozygosity such as fetal/neonatal sex discordance, fresh embryo transfer, and natural cycle FET (in which concomitant spontaneous pregnancy could have occurred). Demographic, clinical and IVF-FET cycle characteristics of the resulting patients were collected. Additionally, a review of the English language literature was performed (PUBMED, PMC) using the search words monozygotic twins, dichorionic diamniotic, in vitro fertilization, and single embryo transfer in order to identify cases of DC-DA monozygotic twinning from 1978 to 2017. Resulting articles were reviewed to eliminate all cases of dizygosity and day 3 embryo transfers. We obtained the following data from the literature search: basic patient demographics, type of fertilization, type and day of embryo transferred, number of embryos transferred, gestational ultrasound details, presence of any genetic testing if performed after delivery, and number of live births. Result(s) Two thousand four hundred thirty-four women underwent fresh or frozen single embryo transfer between June 2012 and June 2017 at the University of California, San Francisco Center for Reproductive Health. Of these, 11 women underwent a single blastocyst transfer with subsequent clinical pregnancies identified as multi-chorionic gestations. Four were in downregulated controlled FET cycles, in which concomitant spontaneous pregnancy could not have been possible. We then reviewed all cases of monozygotic dichorionic-diamniotic (DC-DA) splitting in IVF patients reported in the literature from 1978 to 2017. These eight cases demonstrate monozygotic splitting after the blastocyst stage, which challenges the existing dogma that only monochorionic twins can develop after day 3 post-fertilization. Conclusion(s)The accepted theory of monozygotic twinning resulting from the splitting of an embryo per a strict postfertilization timing protocol must be re-examined with the advent of observed multi-chorionic pregnancies resulting from single blastocyst transfer in the context of IVF.

Purpose Treatment of Asherman syndrome (AS) presents a significant clinical challenge. Based on our in vitro data showing that PRP could activate endometrial cell proliferation and migration, we hypothesized that intrauterine infusion of autologous platelet-rich plasma (PRP) may improve endometrial regeneration and fertility outcomes in patients with moderate-severe AS. Materials and methods Subjects with moderate-severe AS were randomized to PRP or saline control administered following hysteroscopic adhesiolysis. Due to relative inability to randomize patients to the control group, after initial randomization of 10 subjects (6 in PRP and 4 in control groups), the remainder were prospectively enrolled in PRP group (n = 9), with 11 historic controls added to control group, for a total of 30 subjects (PRP n = 15; saline control n = 15). Right after hysteroscopy, 0.5-1 mL of PRP or saline was infused into the uterus via a Wallace catheter, followed by estrogen therapy. The primary outcomes were changes in endometrial thickness (EMT, checked in 3 weeks) and in menstrual flow; secondary outcomes were pregnancy and live birth rates. EMT and menstrual bleeding pattern were assessed before and after the intervention. Pregnancy was assessed over a 6-month period. Results There were no statistically significant differences in age, gravidity/parity, cause of AS, preoperative menses assessment, AS hysteroscopy score, and intrauterine balloon placement between the groups. There was no statistically significant difference (p = 0.79) in EMT pre-PRP infusion for control (5.7 mm, 4.0-6.0) and study arm (5.3 mm, 4.9-6.0). There was no statistically significant change (p = 0.78) in EMT after PRP infusion (1.4 mm, − 0.5-2.4) vs saline (1.0 mm, 0.0-2.5). Patients tolerated the procedure well, with no adverse effects. There was no difference in the predicted likelihood of pregnancy (p = 0.45) between the control (0.67, 0.41-0.85) and study arm (0.53, 0.29-0.76). Conclusions PRP was well accepted and tolerated in AS patients. However, we did not observe any significant EMT increase or improved pregnancy rates after adding PRP infusion, compared to standard treatment only. The use of intrauterine PRP infusion may be a feasible option, and its potential use must be tested on a larger sample size of AS patients.

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Now more than ever in this post COVID-19 era, we should aim to be streamlined and cost effective, prioritising our patients access to outpatient care. This approach could be adopted by other clinical services in Ireland to reduce clinic waiting times.