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Martin CE, Lewis C, Omurtag K. Successful oocyte cryopreservation using letrozole as an adjunct to stimulation in a transgender adolescent after GnRH agonist suppression. Fertil Steril. In press.
) describing the successful cryopreservation of 22 oocytes in a transgender adolescent after pubertal blockade with GnRH agonist is an important addition to the literature (2Martin CE, Lewis C, Omurtag K. Successful oocyte cryopreservation using letrozole as an adjunct to stimulation in a transgender adolescent after GnRH agonist suppression. Fertil Steril. In press.
). Before this, there was only one published case, by Rothenberg et al (3Rothenberg S.S. Witchel S.F. Menke M.N. Oocyte cryopreservation in a transgender male adolescent.), of a transmasculine youth who underwent oocyte cryopreservation while on GnRH agonist therapy. That report, a critical proof of concept that stimulation after puberty blockade is feasible, had a somewhat disappointing outcome with only four oocytes cryopreserved. There are important differences between the two cases that may help extend our understanding. In the current study, they were taken off of the GnRH agonist before ovarian stimulation, whereas in the study of Rothenberg et al. (3Rothenberg S.S. Witchel S.F. Menke M.N. Oocyte cryopreservation in a transgender male adolescent.), the GnRH agonist was maintained. Additionally, Martin et al. (2Martin CE, Lewis C, Omurtag K. Successful oocyte cryopreservation using letrozole as an adjunct to stimulation in a transgender adolescent after GnRH agonist suppression. Fertil Steril. In press.
) reported using high starting gonadotropin doses and Rothenberg et al. (3Rothenberg S.S. Witchel S.F. Menke M.N. Oocyte cryopreservation in a transgender male adolescent.) took the “low and slow approach,” which may explain the outcome partially. Of course, the differences also could be attributable to case-by-case variability, and data are too limited to draw any conclusions about the appropriate management of GnRH agonists at the time of ovarian stimulation and/or the best protocol.Accordingly, we still need to arrive at viable protocols to maximize fertility yields. However, as we work to figure out “what” is effective maximally in terms of gamete preservation, we need to ensure a respectful and comfortable “how.” Minimizing dysphoria during stimulation is critical, as prior studies have demonstrated that fertility preservation processes can be distressing for TGNB youth, even when the individual strongly desired fertility preservation and reported an overall satisfactory experience (4Ethical considerations in fertility preservation for transgender youth: a case illustration.). The study by Martin et al. (2Martin CE, Lewis C, Omurtag K. Successful oocyte cryopreservation using letrozole as an adjunct to stimulation in a transgender adolescent after GnRH agonist suppression. Fertil Steril. In press.
) is the first to describe using letrozole concurrently with ovarian stimulation in this population—a strategy used in oncology to minimize “oncologic burden,” here used in a transgender adolescent to minimize “gender burden” via estradiol elevations. Estradiol levels peaked at 510 pg/mL, and though the patient did experience mild breast enlargement, the tissue atrophied after 3 months of testosterone therapy. Other ways to enhance experience include inclusive signage, training of staff, transabdominal monitoring or pediatric probes, asking about the preferred language to describe genitalia and gametes, maintaining levonorgestrel intrauterine devices or etonorgestrel implants to control bleeding, and using multidisciplinary teams including mental health. Families also should be prepared for a longer than typical stimulation cycle and counseled about the overall lack of data on egg quality in this scenario.Reproductive endocrinologists have long been at the forefront of pushing the frontiers of science in meeting patient needs: in the 1970s with in vitro fertilization, in the 1980s with intracytoplasmic sperm injection, and more recently, with oocyte vitrification and ovarian tissue cryopreservation for fertility preservation, both of which no longer are considered experimental. With proper research oversight to prevent the harms of experimentation, as well as collaboration with TGNB people to ensure respectful treatment and patient-centered care, we can use principles based on known practices and probable extrapolations (e.g., we stimulate people with Kallmann syndrome without difficulty and they often did not go through puberty) to meet patients’ needs with assurances that our steps can move the field forward and are unlikely to cause significant harm. We will never get the data we need without concurrently trying to help the TGNB population build their desired families, so why the apprehension? Just think of where Louise Brown’s parents would be if Edwards, Steptoe, and Purdy had not pushed the boundaries of fertility care back then.
ReferencesEthics Committee of the American Society for Reproductive MedicineAccess to fertility services by transgender persons: an ethics committee opinion.
Fertil Steril. 104: 1111-1115Martin CE, Lewis C, Omurtag K. Successful oocyte cryopreservation using letrozole as an adjunct to stimulation in a transgender adolescent after GnRH agonist suppression. Fertil Steril. In press.
Rothenberg S.S. Witchel S.F. Menke M.N.Oocyte cryopreservation in a transgender male adolescent.
N Engl J Med. 380: 886-887Ethical considerations in fertility preservation for transgender youth: a case illustration.
Clin Pract Pediatr Psychol. 6: 93-100Article InfoPublication HistoryPublished online: July 08, 2021
Publication stageIn Press Corrected ProofFootnotesYou can discuss this article with its authors and other readers at https://www.fertstertdialog.com/posts/33241
IdentificationDOI: https://doi.org/10.1016/j.fertnstert.2021.06.020
Copyright©2021 American Society for Reproductive Medicine, Published by Elsevier Inc.
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