We consider that fertility counseling is effected by the legal, ethical and cultural background in every country. Therefore this guide has no strict rules or fixed regulations. The recommendations are based on the latest evidence and are a proposal for a counseling framework. The first part focuses on communication, and the second part focuses on the impact of medical transition on fertility and fertility preservation options.
Timing; Offer fertility counseling as early as possible, at least before the start of PS, GAHT or GAS. Continue offering fertility counseling repeatedly over time since reproductive wishes might changes over time. However, it’s important to note that offering fertility counseling should not be pronatalist nor gatekeeping (Chen et al., Citation2019; Light et al., Citation2018; Stolk et al., Citation2023).
Language; Use chosen names and pronouns correctly and consistently. Use gender-neutral, non-binary and gender-sensitive language where appropriate. For example, try to replace semen and oocytes with gametes to make less reference to gendered assumptions about gametes. Make sure to know and understand the basic terms and concepts within TGD communities or ask the patient the (medical) terms they would like to use during the consultation (Armuand et al., Citation2017).
Environment; Provide a safe, non-judgmental and culturally sensitive environment. This may inclue the provision of appropriate information pamphlets, bathrooms, and training of (non)medical staff. In the consultation room make sure that TGD people feel respected and heard and be open to engage in discussion that may cause some discomfort for you as clinician (Ellis et al., Citation2015; Lai et al., Citation2021).
Developmental stages; Assess current fertility knowledge, understanding and ability to consider the future. Provide developmentally appropriate information for adolescents and young adults. Evaluate the adolescent’s ability to consider their future and explore their understanding of the consequences of their decision (Harris et al., Citation2020; Kyweluk et al., Citation2018).
Information; Act as knowledgeable providers of objective information and do not encourage or discourage fertility preservation based on your own assumptions. Make sure that TGD people keep their autonomy and give notice to their own view on parenthood (Armuand et al., Citation2017; Bartholomaeus & Riggs, Citation2020; Kerman et al., Citation2021).
Journey to parenthood; Include the whole journey to parenthood in the conversation. Pay attention to their reproductive capacity, the option to carry a pregnancy, the importance of genetic offspring, and parenting desire and partnering possibilities (i.e. sexual attraction). Identify other parenting options, including choosing not to parent, adoption, fostering, donor gametes or surrogacy, and discuss the legal and financial implications of each option (Boguszewski et al., Citation2022; Chen et al., Citation2019; Lai et al., Citation2021; Stolk et al., Citation2023).
Pregnancy; Oocyte maturation and ovulation is possible during or after testosterone treatment and (un)intended pregnancies may occur. When retaining uterus and ovaries most individuals are physically able to conceive and carry a pregnancy even after long-term testosterone use (Ellis et al., Citation2015; Light et al., Citation2014; Moseson et al., Citation2021). However, testosterone therapy may be contraindicated during pregnancy or while attempting to become pregnant given its potential virilizing effects on the fetus (Muthusamy et al., Citation2010). Therefore, testosterone should be discontinued 3 months before trying to conceive.
Pre-, peri- and postpartal care; Since there is an increased risk of depression and dysphoria during and after pregnancy (Hoffkling et al., Citation2017; van Amesfoort et al., Citation2023), we advise gender-affirming preconception care, prenatal counseling, obstetric care, labor and delivery, chest/breast feeding supportive services and postpartum guidance (Coleman et al., Citation2022).
Retaining ovaries; Studies show mixed results but overall no damage to the ovarian tissue and an active ovarian functioning after long term testosterone treatment. Therefore we suggest it is safe to retain ones ovaries to preserve fertility (Kumar et al., Citation2022).
Timing of oocyte/embryo vitrification; Studies show no difference in outcomes between TGD people who pursued oocyte cryopreservation prior to or after starting testosterone, even after long-term testosterone exposure of more than 10 years (ranging from 10 to 17 years) (Amir, Yaish, Samara, et al., Citation2020; Israeli et al., Citation2022; Leung et al., Citation2019). Therefore, it is mostly a personal choice for people to pursue fertility preservation before or after the start of GAHT. For example, barriers for pursuing fertility preservation after the start of testosterone are temporarily discontinuation of testosterone or the future wish for GAS.
Oocyte/embryo vitrification; Prepare TGD people for internal vaginal examinations (if transrectal or transabdominal ultrasound is not feasible/available), daily hormone (FSH, hMG, GnRHa, r-hCG) injections, resulting in elevated estradiol levels, return of blood loss and the ovarian pick-up method which is transvaginal. The ovarian pick-up can be either with or without sedation depending on the availability of anesthesia. When anesthesia is not available the ovarian pick up might cause severe distress and pain (Asseler et al., Citation2023).
Result of oocyte/embryo vitrification; Discuss the number of retrieved and vitrificated oocytes. In cis women, the oocyte-to-baby rate/live birth rate is around 20 oocytes (Martin et al., Citation2010; Stoop et al., Citation2012). However, this is largely depended on age. A more recent observational study found a similar live birth rate in the group between 6 and 15 oocytes compared to 16–25 (Bahadur et al., Citation2023). So far, this is not studied in TGD people. In a case series of seven TGD people, the live birth rate was 100% with a mean retrieved oocytes of 14.3 ± 6.1 SD (Leung et al., Citation2019). As a consequence, multiple rounds of hyperstimulation are sometimes necessary to obtain the desired amount of oocytes.
Testosterone use; For both oocyte/embryo cryopreservation and pregnancy we suggest a cessation of approximately 3 months (time of full oocyte maturation/taking into account the ∼70 days from antral follicle formation to ovulation) when using testosterone. Though, the optimal wash-out period is unknown, testosterone exposed oocytes from TGD people show an impaired fertilization rate and embryo development (Bailie et al., Citation2023; Lierman et al., Citation2021). However, several cases show successful oocyte vitrification without discontinuation (Cho et al., Citation2020; Gale et al., Citation2021; Greenwald et al., Citation2022; Moravek et al., Citation2023; Stark & Mok-Lin, Citation2022). So, when the dysphoria of cessation testosterone is too much, after shared-decision making and counseling for the unknown effects of testosterone on the oocyte, one can opt for continuing testosterone during ovarian stimulation preferably within a research protocol, until better evidence is provided. Testosterone or other masculinizing hormone therapy should be discontinued prior to and through any pregnancy.
Blood loss; To prevent (potential) distress due to menses during testosterone cessation a progestins or GnRH agonist can be used (Stolk et al., Citation2023). Before ovarian stimulation a menses is not required when a direct embryo transfer into the uterus is not planned (Moravek et al., Citation2023).
Estradiol peak; If PS was started at Tanner stage 2 or 3 an aromatase inhibitor to limit the peak estradiol levels may potentially result in less chest tissue growth when a mastectomy is not (yet) performed (Martin et al., Citation2021). We suggest to study this in a research protocol to first prove the effect and safety.
Colpectomy; After removing of the vaginal tissue transvaginal ultrasound and pick-up is no longer feasible and needs to be transabdominal ultrasound-guided or laparoscopic, this results into a higher complication risk during ovum pick-up and a lower number of retrieved oocytes.
Adolescents; Fertility preservation is not necessary in assigned female at birth adolescents since they can most likely pursue this at a later age if they are willing to temporarily discontinue testosterone at that time. Due to the invasiveness of the procedure it may be disruptive to perform the procedure in virgo/very young patients, nonetheless it is technically possible and successful (Amir, Oren, et al., Citation2020) also after using PS (Insogna et al., Citation2020; Martin et al., Citation2021).
Ovarian cortex cryopreservation; In vitro maturation (IVM) is still experimental due to unsuccessful fertilization techniques (Lierman et al., Citation2021). Currently, ovarian cortex is only successful with autologous transplantation (Dolmans et al., Citation2021), which is no feasible option for most TGD people. For young adults ovarian hyperstimulation is not always feasible before oophorectomy, due to increasing gender dysphoria triggered by internal examinations, hormone injections, and bleeding. For these persons ovarian cortex preservation may be considered, with possible future techniques for IVM in sight. For some autologous transplantation may be an option in the future if their desire for children develops in the absence of IVM strategies at that time.
Eliran Mor MDCosts; In countries were fertility preservation is offered by health care insurance there is a higher fertility preservation rate (Amir, Yaish, Oren, et al., Citation2020; Brik et al., Citation2019; Mattelin et al., Citation2022). In the countries with self-pay the main barrier for pursuing fertility preservation are costs (Rogers et al., Citation2021).
Future gamete use; The use of stored gametes is largely depended on the gametes of the future partner, the carrier (e.g. TGD person themselves, partner or gestational carrier) and the use of donor gametes. Before the start of fertility preservation we advise to discuss the options related to the patient.
Oocyte donation; If the pregnancy is carried by a partner or gestational carrier via oocyte donation of the TGD person we advise to discuss the medical risks (i.e. higher risk for pre-eclampsia (Keukens et al., Citation2022) and the legal and ethical difficulties of oocyte donation.
Timing; We advise sperm banking before the start of PS or GAHT. Since most adolescents continue with GnRH agonist (van der Loos et al., Citation2022) as anti-androgen, spermatogenesis will never be initiated (de Nie et al., Citation2022) and after starting GAHT most studies show impaired or absent spermatogenesis (Jiang et al., Citation2019; Jindarak et al., Citation2018; Leavy et al., Citation2017; Sinha & Ferrando, Citation2020).
Results of cryopreservation; Studies show an impaired semen quality before the start of GAHT. Therefore we advise to evaluate trans specific life-style factors (e.g. ejaculation frequency, wearing tight undergarments, and tucking) and discuss the different semen quality outcomes and consequences of intrauterine insemination (IUI), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for future use. For example, if the semen quality is low, discuss a cessation of tucking for 3 months (time to full regeneration) before obtaining a new semen specimen. Taken into consideration what the impact of these adaptations mean for someone’s personal life.
Restoring spermatogenesis; PS reversibly inhibits spermatogenesis but, there is limited evidence on the time to restore spermatogenesis after starting PS (Adeleye et al., Citation2023; Peri et al., Citation2021). For GAHT the timeline is uncertain and can vary widely (3–18 months) based on the type of anti-androgen therapy that was used (Adeleye et al., Citation2019; de Nie et al., Citation2023; Sermondade et al., Citation2021). In presents of the testis, conception via penis-vagina intercourse after discontinuing GAHT is still successful (de Nie et al., Citation2023). For both sperm banking and conception via intercourse we suggest semen analysis every 3 months after discontinuing GAHT.
Azoospermia; Testicular sperm extraction (TESE) may be performed when there is a non-obstructive azoospermia during sperm banking via masturbation or an inability for masturbation due to severe genital dysphoria. First, optimize (trans specific) life-style factors for 3 months, if present, similar to semen cryopreservation before performing a TESE.
Adolescents; TESE is an option for adolescents in early puberty who are not able to physically or mentally perform a semen sample via masturbation. This is probably successful from Tanner 3–4, with testicular volume > 10 ml (Peri et al., Citation2021) and therefore may require a delay in the start of PS. A TESE may be combined with placement of the subcutaneous GnRH agonist implant. Children born after TESE-ICSI procedure from cisgender males show no long-term effects on development and health outcomes (Meijerink et al., Citation2016).
Testicular tissue cryopreservation; Spermatogonial stem cells or testicular tissue cryopreservation are still experimental for both autologous transplantation and IVM (Wyns et al., Citation2021). Since autologous transplantation is not possible after orchiectomy TGD people will be depended on IVM.
Costs; In countries were fertility preservation is coffered by health care insurance there is a higher fertility preservation rate (Amir, Yaish, Oren, et al., Citation2020; Brik et al., Citation2019; Mattelin et al., Citation2022). In the countries with self-pay the main barrier for pursuing fertility preservation are costs (Rogers et al., Citation2021).
Future gamete use; The use of stored gametes is largely depended on the gametes of the future partner, the carrier (e.g. partner with uterus or gestational carrier) and the use of donor gametes. Before the start of fertility preservation we advise to discuss the options related to the patient.
TGD people may have different desires, values, challenges and considerations concerning parenthood compared to cisgender people. During their transition TGD people may experience changes in their fertility desires as they explore their gender identity and undergo medical transition. Therefore, it is of utmost importance that all TGD people have access to gender sensitive and culturally competent fertility counseling and preservation before and during their medical transition. Fertility preservation is a crucial aspect of transgender healthcare that enables TGD people to have the option of geneticparenthood. Fertility preservation still holds lots of barriers for TGD people. For example, lack of access to healthcare services, discriminatory laws that prohibit assisted reproductive technology, adoption, or surrogacy for TGD people and financial constraints by insufficient healthcare insurance. To promote equitable access to reproductive healthcare for all TGD people, it is crucial to challenge unjust laws and policies and replace them with evidence-based, inclusive practices.
Adeleye, A. J., Stark, B. A., Jalalian, L., Mok-Lin, E., & Smith, J. F. (2023). Evidence of spermatogenesis in the presence of hypothalamic suppression and low testosterone in an adolescent transgender female: A case report. Transgender Health, 8(1), 104–107. https://doi.org/10.1089/trgh.2021.0034
Anderson, R. A., Amant, F., Braat, D., D'Angelo, A., Lopes, S. M. C. D., Demeestere, I., Dwek, S., Frith, L., Lambertini, M., Maslin, C., Moura-Ramos, M., Nogueira, D., Rodriguez-Wallberg, K. (2020). ESHRE guideline: Female fertility preservation. Human Reproduction Open, 2020(4), hoaa052. https://doi.org/10.1093/hropen/hoaa052
Bahadur, G., Homburg, R., Jayaprakasan, K., Raperport, C. J., Huirne, J. A. F., Acharya, S., Racich, P., Ahmed, A., Gudi, A., Govind, A., & Jauniaux, E. (2023). Correlation of IVF outcomes and number of oocytes retrieved: A UK retrospective longitudinal observational study of 172 341 non-donor cycles. BMJ Open, 13(1), e064711. https://doi.org/10.1136/bmjopen-2022-064711
Bailie, E., Maidarti, M., Hawthorn, R., Jack, S., Watson, N., Telfer, E., & Anderson, R. (2023). The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool. Reproduction and Fertility, 4(2), 335. https://doi.org/10.1530/RAF-22-0102
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