ART outcomes in female to male transgender patients: a new frontier in reproductive medicine

Abstract

BACKGROUND: Surmounting evidence suggests that frozen embryo transfer results in higher pregnancy and live birth rates compared to fresh transfer during in vitro fertilization (IVF) (1, 2). There is conflicting data regarding neonatal outcomes: preterm birth, pre-eclampsia and birth weight (3, 4). The effect of embryo cryopreservation on the placental morphology is not well understood. OBJECTIVE: To evaluate differences in placental morphology from infants conceived with cryothaw compared to fresh transfer in IVF. MATERIALS AND METHODS: A retrospective cohort study from 2009 through 2015 of live births resulting from IVF with autologous oocytes. The placentas were divided into two groups, those from cryothaw embryo transfers and those from fresh embryo transfers. Gross and histologic placental specimens were examined. Morphologic pathology was categorized into anatomic (e.g. cord malinsertion or circumvallate), infectious (choramnionitis), inflammatory (e.g. villitis of unknown etiology, deciduitis), and vascular/thrombotic (placental abruption, intervillous thrombus, maternal and fetal vascular malperfusion). T-tests and Chi square were used for analysis with 95% confidence intervals (CIs). Logistic regression modeling was used to control for age, race, body mass index, fertility diagnosis and gestational age gestational age at delivery. RESULT(S): A total of 838 placentas were reviewed; 13% from cryothaw transfers and 87% from fresh transfers. Gestational age was similar between the two groups, (38.5 vs. 37.7 weeks p¼ 0.2). The mean birth weight of singleton infants was higher in the cryothaw group (3241.6 grams) than in the fresh group (3099.5 grams, p¼0.001). There was no difference in the proportion of placentas submitted to pathology in frozen vs. fresh group (36% vs. 40%, p>0.05). Controlling for regression modeling, there were fewer vascular/thrombotic morphologies in the cryothaw transfers when compared to the fresh (aOR¼0.31, CI¼0.11-0.81, p<0.05). There were also fewer anatomic morphologies in the cryothaw group as compared to the fresh group (aOR¼ 0.24.

Short-term testosterone use in female mice does not impair fertilizability of eggs: implications for the fertility care of transgender males

“…Transgender men who have been undergoing testosterone therapy and who wish to obtain eggs for fertilization or freezing are generally stimulated with gonadotropins. This is usually done following a period of T cessation that is sufficient for the menstrual cycle to resume (Adeleye et al, 2019;Broughton and Omurtag, 2017;Leung et al, 2018). There is strong evidence that transgender men who have taken T can produce viable, developmentally competent eggs after discontinuing its use (Adeleye et al, 2019;Broughton and Omurtag, 2017;Leung et al, 2018;Light et al, 2014), but to date, there are no publications regarding the quality and developmental capacity of eggs retrieved from transgender men who remain on HT.…”

“…However, the ovarian tissue follicular pool is not diminished (De Roo et al, 2016;Van Den Broecke et al, 2001) (Light et al, 2014). Case reports have been published of subjects successfully undergoing IVF after temporarily discontinuing testosterone therapy for 1-12 months, and healthy live births were reported (Adeleye et al, 2019;Broughton and Omurtag, 2017;Leung et al, 2018). These data suggest that the follicular pool and oocyte quality are preserved.…”

“…Accordingly, if a transgender male presents for fertility treatment now or in the near future and plans to have the pregnancy carried by a cis-female partner or gestational carrier, the best option is in vitro fertilization (IVF) after ovarian stimulation and oocyte retrieval. Due to the unknown effects of high-level testosterone on ovarian response and oocyte quality, the current recommended practice before IVF is discontinuation of testosterone to allow the resumption of menses (Adeleye et al, 2019;Broughton and Omurtag, 2017;Leung et al, 2018). While this treatment regimen can be effective, HT cessation for the purpose of fertility treatment has been reported to cause significant psychological distress in the form of gender dysphoria attributed to the genderincongruous effects of testosterone withdrawal, estrogen exposure, and menses (Armuand et al, 2017).…”

Testosterone use in female mice does not impair fertilizability of eggs: Implications for the fertility care of transgender males

“…Accordingly, if a transgender male 73 presents for fertility treatment now or in the near future and plans to have the pregnancy carried 74 by a cis-female partner or gestational carrier, the best option is in vitro fertilization (IVF) after 75 ovarian stimulation and oocyte retrieval. Due to the unknown effects of high-level testosterone 76 on ovarian response and oocyte quality, the current recommended practice before IVF is 77 discontinuation of testosterone to allow the resumption of menses (Adeleye et al, 2019;78 Broughton and Omurtag, 2017; Leung et al, 2018). While this treatment regimen can be 79 effective, HT cessation for the purpose of fertility treatment has been reported to cause 80 significant psychological distress in the form of gender dysphoria attributed to the gender-81 incongruous effects of testosterone withdrawal, estrogen exposure, and menses (Armuand et 82 al., 2017).…”

“…The difference in 366 E2 levels after eCG was surprising because a similar number of oocytes were collected after 367 stimulation. In human IVF cycles, the peak E2 level achieved directly correlates with the 368 number of oocytes collected at the time of retrieval (Chenette et al, 1990), and during reported 369 IVF cycles in transgender males, the peak E2 levels, as well as the number of oocytes 370 collected, have been reported to be similar to female controls, although higher doses of 371 gonadotropins were used for transgender males (Leung et al, 2018). Lower E2 levels here may 372 reflect the lower number of CLs in the T group.…”