Fertility preservation provision in the NHS in Scotland: guidance

Annex D

Fertility Preservation for transgender and non-binary people

While it is preferable for transgender and non-binary people to store eggs or sperm before starting gender-affirming hormone treatment, sometimes this is not possible, and consideration must be given to how best to manage that situation. In some cases, it may be considered more appropriate to defer gamete storage (perhaps for years) despite imminently starting gender-affirming hormone treatment, to allow continuing consideration of the wish for such storage. Gamete storage can be considered at any time up until surgical removal of the gonads.

For egg cryopreservation

The procedures required prior to oocyte cryopreservation, such as hormonal ovarian stimulation and transvaginal ultrasound (TVS), can have a negative impact on gender dysphoria; successful management requires sensitivity and awareness of these issues, e.g. offering transabdominal ultrasound monitoring (Armound et al 2017).

Patients may be on testosterone, and some also on GnRH agonists. Thus, they will be hypogonadotrophic, much like women on long-term agonists e.g. for endometriosis. Importantly, intrafollicular testosterone concentrations are 100-200 nmol/l (Kristensen et al 2018), thus serum testosterone concentrations are not relevant to the huge concentrations that the oocyte is exposed to during normal development.

Options for ovarian stimulation:

1. For many of these young patients (who will have a high ovarian reserve), an antagonist cycle with GnRH trigger will be appropriate.

2. It is very important to consider if there is pituitary suppression, resulting in likely non-response to GnRHa trigger. In that case, hCG trigger will be needed.

3. For some patients on long-term GnRHa treatment, it may be appropriate to stop that medication in advance of ovarian stimulation, or to continue it and use a down-regulation protocol. This may be associated with an increased risk of OHSS where the ovarian reserve and response is high.

4. Add letrozole (e.g. 5mg daily) during stimulation to minimise E2 rise. There is evidence that slightly greater follicle growth before trigger is of value (eg 2 x19mm or 3 x18mm)

5. Lower testosterone dosage while maintaining some gender-affirming effect can be achieved by using testosterone gel at e.g. 25mg/day for two to three months before ovarian stimulation. This is likely to allow at least partial recovery of gonadotrophin section and ovarian activity, which may have a positive effect on the response to ovarian stimulation.

Thus, a routine requirement to stop gender-affirming testosterone therapy before starting ovarian stimulation is not necessary. This is the practice in other centres with substantial experience of this (e.g. Karolinska Institute, Stockholm), and successful egg recovery while the patient continues on testosterone treatment has been reported (Cho et al 2020).

For sperm cryopreservation

Patients may be on long-term GnRH agonists and oestradiol treatment. They will be hypogonadotrophic, and spermatogenesis is likely to be suppressed (though not always completely). There is also some evidence that even before endocrine treatment is started, trans women are more likely to show oligospermia (Li et al 2018). The procedures for sperm cryopreservation can have a negative impact on gender dysphoria; successful management requires sensitivity and awareness of these issues.

Options

1. Assess sperm production at presentation. If there are sperm present, store them. More than one semen sample may be needed to ensure an adequate number of sperm are stored (as with cancer patients).

2. If severe oligo/azoospermia, discuss stopping endocrine treatment. It may take many months for spermatogenesis to be restored, and stopping treatment may not be acceptable to some patients.

3. If they do accept to stop treatment, it seems reasonable to offer a repeat assessment at three to six months and at intervals thereafter, until sufficient sperm can be stored.

References

Armuand G, Dhejne C, Olofsson JI, Rodriguez-Wallberg KA Transgender men’s experiences of fertility preservation: a qualitative study. Hum Reprod. 2017;32:383-390

Cho K, Harjee R, Roberts J, Dunne C. Fertility preservation in a transgender man without prolonged discontinuation of testosterone: a case report and literature review. Fertil Steril. 2020; 14:43-47.

Kristensen SG, Mamsen LS, Jeppesen JV, Bøtkjær JA, Pors SE, Borgbo T, Ernst E, Macklon KT, Andersen CY. Hallmarks of Human Small Antral Follicle Development: Implications for Regulation of Ovarian Steroidogenesis and Selection of the Dominant Follicle. Front Endocrinol (Lausanne). 2018 12:376.

Li K, Rodriguez D, Gabrielsen JS, Centola GM, Tanrikut C Sperm cryopreservation of transgender individuals: trends and findings in the past decade. Andrology. 2018; 6:860-864.