Table 1.
Fertility Preservation Outcomes in Transgender Men After/During Prolonged Testosterone Therapy
| Reference | Study type and design | Population | Testosterone therapy duration | Ovarian stimulation protocol/fertility preservation technique | Oocyte retrieval outcomes |
|---|---|---|---|---|---|
| Discontinuation of testosterone therapy for fertility preservation | |||||
| Gidoni et al.27 | Case report | Transgender man (age, 37 years). Transvaginal ultrasound revealed a 5 mm endometrial thickening, reduced ovarian size, and low follicular reserve. |
Testosterone enanthate administration (250 mg) every 16 days for 168 consecutive months before fertility therapy. | Two cycles of ovarian stimulation with oocyte retrieval for IVF and subsequent embryo cryopreservation. Testosterone suspension for 4 months. GnRH agonist protocol for ovarian stimulation. |
First cycle: Retrieval of 12 MII oocytes, out of which 7 were fertilized, and 4 of these were cryopreserved. Second cycle: Retrieval of 15 MII oocytes, out of which 14 were fertilized, and 12 of these were cryopreserved. |
| Insogna et al.28 | Case report | Transgender man (age, 21 years). Patient with 14 months of amenorrhea after initiation of hormone therapy. Serum AMH levels of 1.06 ng/mL while on testosterone therapy. |
Testosterone administration for 24 consecutive months before fertility therapy. | Two cycles of ovarian stimulation with oocyte retrieval for cryopreservation. Testosterone suspension for ∼3 months. First cycle: Administration of rhFSH (225 IU) and hMG (225 IU). A GnRH antagonist was administered on day 8, followed by hCG (10,000 IU) injection and oocyte retrieval on day 10. Second cycle: Administration of diluted leuprolide acetate (10 IU twice daily), rhFSH (225 IU), and hMG (225 IU). On day 11, hCG (10,000 IU) was administered and oocytes were retrieved. |
First cycle: Retrieval of 11 oocytes, out of which 10 were cryopreserved, and 6 of these were mature (MII). Second cycle: Retrieval of 14 oocytes, out of which 6 were mature (MII). |
| Broughton and Omurtag29 | Case report | Transgender man (age, 30 years). Patient with amenorrhea at fertility therapy initiation. Ultrasound revealed normal uterus and AFC of 25. | Testosterone administration for 26 consecutive months before fertility therapy. | Ovarian stimulation with oocyte retrieval for IVF and subsequent embryo transfer into the uterus of his cisgender partner. Testosterone discontinuation for a more than 3-month period. Fertility preservation protocol: Day 1: Administration of oral contraceptive for 2 weeks. Subsequent administration of GnRH antagonist. Day 8: hCG administration and oocyte retrieval. |
Retrieval of 16 oocytes. Of these, 13 were mature oocytes (MII), and 7 of these were successfully fertilized. |
| Resende et al.30 | Case report | Transgender man (age, 34 years). Patient with amenorrhea at fertility therapy initiation. | Testosterone administration (250 mg) for 24 consecutive months before fertility therapy. | Ovarian stimulation with oocyte retrieval for IVF and subsequent embryo transfer into the uterus of his cisgender partner. Testosterone was discontinued until menses resumption. The exact duration of androgen suspension is not stated. Fertility preservation protocol: Day 1: Administration of folic acid, and rhFSH with rhLH in 2:1 ratio. Day 3: Increase of rhFSH dose (150 IU) and administration of hMG (75 IU). Day 8: Pituitary blockade by administration of cetrotide (1.5 mg daily). Day 10: Increase of rhFSH dose (225 IU) with the same hMG dosage (75 IU). Day 12: hCG administration and oocyte retrieval. |
Retrieval of 16 oocytes. Of these, 13 were mature oocytes (MII) and successfully fertilized. |
| Cho et al.31 | Case report | Transgender man (age, 28 years). Transabdominal ultrasound revealed normal ovaries and uterus. Serum AMH levels of 2.50 ng/mL while on testosterone therapy. |
Testosterone administration (0.6 mg weekly) for 36 consecutive months before fertility therapy. | Ovarian stimulation with oocyte retrieval for cryopreservation. Testosterone suspension for 24 days with oral administration of letrozole (7.5 mg) from the beginning until 7 days after oocyte retrieval. Fertility preservation protocol: Day 1: Testosterone suspension. Day 5: Daily administration of ganirelix acetate (0.25 mg). Day 7: Subcutaneous administration of rhFSH (300 IU) and hMG (150 IU) for 13 consecutive days. Day 14: Administration of hCG (5000 IU), triptorelin (175 IU daily), and rhFSH (300 IU) when follicles reached 17 mm. Transvaginal oocyte retrieval was carried out 36 h after hCG injection. |
Retrieval of 13 oocytes, out of which 11 were mature (MII) and subsequently vitrified. |
| Leung et al.32 | Retrospective cohort study | 26 transgender men (mean age, 28.3±6.7 years), of whom 16 reported testosterone administration before fertility counseling. Mean serum AMH levels of 3.4±1.9 ng/mL. |
Mean duration of 43.9±31.0 months on testosterone therapy within the 16 transgender men undergoing hormone treatment. | Ovarian stimulation for oocyte retrieval and ovarian tissue cryopreservation with subsequent IVF. Testosterone suspension for 4.5±3.5 months (range 1–12 months). The ovarian stimulation protocol is not described. |
Retrieval of 18.6±9.3 oocytes, of which 77.0%±23.3% were mature (MII). |
| Fertility preservation undergoing testosterone therapy | |||||
| Lierman et al.19 | Cross-sectional study | 16 transgender men (mean age, 24.30±6.15 years). The study population was divided into three groups: (1) 4 subjects aged <20 years. (2) 9 subjects aged 20–30 years. (3) 3 subjects aged >30 years. |
Mean duration of 13.4±5.25 months on testosterone therapy at the moment of the oophohysterectomy. | Hysterectomy and bilateral oophorectomy for ovarian tissue cryopreservation and in vitro oocyte maturation. Protocol without suspension of testosterone therapy. |
Mean retrieval of 42.5 COCs for all individuals (n=16). (1) Subjects aged <20: 61.3±76.2 oocytes retrieved. (2) Subjects aged 20–30: 41.0±35.7 oocytes retrieved. (3) Subjects aged >30: 22.0±5.0 oocytes retrieved. |
| Gale et al.33 | Case report | Transgender man (age, 20 years). Transabdominal ultrasound revealed normal ovaries and uterus, with an AFC >40. Serum AMH levels of 19.9 ng/mL while on testosterone therapy. |
Testosterone administration (25 mg weekly) for 18 consecutive months before fertility therapy. | Ovarian stimulation with oocyte retrieval for cryopreservation. Protocol without suspension of testosterone therapy. Fertility preservation protocol: Day 1: Administration of cetrorelix with rhFSH (175 IU daily) and rhLH (75 IU daily). Day 9: Administration of leuprolide acetate (3 mg) and initiation of four doses of cabergoline (0.5 mg every third day). Transvaginal oocyte retrieval 36 h after leuprolide injection. |
Retrieval of 25 COCs. Of these, 22 MII oocytes were successfully cryopreserved. |
| Greenwald et al.34 | Case report | Transgender man (age, 33 years). Hysterosonography and serum AMH levels while on testosterone revealed an ovarian reserve above normal for age. | Testosterone administration (50 mg weekly) for 120 consecutive months before fertility therapy. | Ovarian stimulation with oocyte retrieval for reciprocal IVF. Protocol without suspension of testosterone therapy. Fertility preservation protocol: Day 1: Daily subcutaneous administration of rhFSH (300 IU), hMG (150 IU), and ganirelix acetate. Day 14: Induction of oocyte maturation by subcutaneous injection of leuprolide acetate (40 IU) and hCG (1000 IU). Transvaginal oocyte retrieval 36 h after leuprolide and hCG injection. |
Retrieval of 20 oocytes, of which 16 were mature (MII), and 13 were successfully fertilized. Subsequent to IVF, 5 embryos progressed to blastocysts, and 4 exhibited aneuploidy. |
| De Roo et al.35 | Prospective cohort study | 40 transgender men (mean age, 24.30±6.15 years). Subjects exhibited amenorrhea for an average of 70.59±31.89 weeks. Mean serum AMH levels of 4.66±3.84 ng/mL while on testosterone therapy. |
Mean duration of 13.39±6.11 months on testosterone therapy at the moment of the oophohysterectomy. | Hysterectomy and bilateral oophorectomy for ovarian tissue cryopreservation and in vitro oocyte maturation. Protocol without suspension of testosterone therapy. |
From the 40 transgender men, an average of 37.51±33.58 oocytes were retrieved. |
| Lierman et al.36 | Cross-sectional study | 83 transgender men (mean age, 20.0 [min: 17.6; max: 38.4] years). Serum AMH levels of 2.8 ng/mL while on testosterone therapy. |
Mean duration of 20.75 months on testosterone therapy at the moment of the oophohysterectomy. | Hysterectomy and bilateral oophorectomy for ovarian tissue cryopreservation and in vitro oocyte maturation. Protocol without suspension of testosterone therapy. |
Mean retrieval of 23.0±15.8 COCs. |
| Comparison of fertility outcomes among transgender men | |||||
| Amir et al.37 | Retrospective cohort study | 12 transgender men divided into two groups: (1) 6 transgender men with no history of hormone treatment (mean age, 23.3±4.0 years). (2) 6 transgender men undergoing testosterone therapy (mean age, 30.3±3.8 years). |
Among the 6 individuals on hormone treatment, a mean duration of 7.0±55.3 months on testosterone therapy was reported before fertility therapy. | Ovarian stimulation with oocyte retrieval for cryopreservation and IVF. Mean testosterone suspension for 9.3±5.6 months. Fertility preservation protocol: Daily administration of rhFSH from the third day of menses resumption. GnRH antagonist administration: initiation of therapy with cetrorelix acetate (0.25 mg) from the time E2 levels reached >450 pg/mL and a follicular diameter ≥12 mm was achieved. GnRH agonist administration: Following cetrorelix acetate, triptorelin (0.2 mg/day) was administered at the time follicular diameter >18 mm was evident for at least three follicles. Transvaginal oocyte retrieval was carried out 36 h after triptorelin injection. |
From the group of 6 transgender men on testosterone therapy, 22±9.94 oocytes were retrieved on average. The number of oocytes retrieved did not reveal a significant difference between the two groups (p=0.651). |
| Adeleye et al.38 | Retrospective cohort study | 13 transgender men (mean age, 22.4 years) divided into two groups: (1) 6 transgender men with no history of hormone treatment (2) 7 transgender men undergoing testosterone therapy |
Among the 7 individuals on hormone treatment, a mean duration of 46 months on testosterone therapy was reported before fertility therapy. | Ovarian stimulation with oocyte retrieval for cryopreservation. Mean testosterone suspension for 6 months. Ten ovarian stimulation cycles with GnRH antagonist protocol and average duration of 10 days (range 8–14 days). |
From the group of 7 transgender men on testosterone therapy, an average of 12 mature oocytes (MII) were retrieved and exhibited a maturation rate of 92%. The number of oocytes retrieved did not reveal a significant difference between the two groups (p=0.148). |
AFC, antral follicular count; AMH, anti-Müllerian hormone; COCs, cumulus–oocyte complexes; E2, estradiol; GnRH, gonadotropin-releasing hormone; hCG, human chorionic gonadotropin; hMG, human menotropin; IVF, in vitro fertilization; MII, metaphase II; rhFSH, recombinant human follicle-stimulating hormone; rhLH, recombinant human luteinizing hormone.