“Lights and Shades” of Fertility Preservation in Transgender Men Patients: A Clinical and Pathological Review
Abstract
:1. Introduction
2. Materials and Methods
3. Fertility Preservation Options for Transgender Men
- Oocyte/Embryo cryopreservation;
- Ovarian tissue cryopreservation (OTC) and in vitro maturation (IVM).
3.1. Oocyte/Embryo Cryopreservation
3.2. Ovarian Tissue Cryopreservation and In Vitro Maturation
3.2.1. Ovarian Tissue Cryopreservation
3.2.2. In Vitro Maturation
3.2.3. Fertility Preservation Outcomes in Transgender Men Patients
4. Psychological and Emotional Impact of FP on Transgender Men Patients
5. Histopathological Changes in Genital Organs and in Breast after HT
6. Effects of Gender-Affirming Hormonal Therapy (GAHT) on the Ovaries
7. Impact of GAHT on the Uterus
8. Impact of GAHT on Mammary Tissue
9. Discussion and Possible Future Approaches
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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---|---|---|---|---|---|
Sapino et al. [32] | 2 transgender men | No control | Histologic | Mean: 30 months | Epithelial atrophy; in patient 2, apocrine metaplasia; and hyalinosis of periductal and interlobular stroma. |
Burgess et al. [33] | 29 transgender men | 10 cisgender men patients with gynecomastia and 10 cisgender healthy women | Histologic | At least 18 months | Normal acini (28/29), normal ducts (29/29), fibrosis (29/29), cysts (13/29), apocrine metaplasia (15/29), epithelial hyperplasia (9/29), and microcalcification (8/29). |
Slagter et al. [34] | 23 transgender men | 10 cisgender women | Histologic | 18–24 months | Marked reduction in glandular tissue, involution of the lobuloalveolar structures, prominence of fibrous connective tissue, and reduction in fat tissue. |
Ramos et al. [35] | 34 transgender men | Expected results in cisgender women according to American College of Radiology—Breast Imaging Reporting and Data System (ACR BI-RADS®). | Mammography and breast ultrasound | Not available | Higher frequency of dense breast in transmen (66–6%) compared to expected results for cisgender women. |
Study ID | Population | Control | Assessment | Average Duration of HT Intake | Findings |
---|---|---|---|---|---|
Amirikia et al. [36] | 10 transgender men | 3 PCO and 3 cisgender women | Histologic | 14 to 84 months (mean: 35 months) | Thickening of tunica albuginea and basal membrane (PCOS-like). |
Futterweit et al. [37] | 19 transgender men | 12 age-matched cisgender women | Histologic | 12 to 120 months (mean: 37 months) | PCOM (13/19), multiple cystic follicles (17/19), diffuse ovarian stromal hyperplasia (16/19), collagenization of the outer cortex (13/19), and luteinization of stromal cells (5/19). |
Miller et al. [38] | 32 transgender men | 36 cisgender women | Histologic | 12 to 96 months | Normal number of primordial follicles, follicular cysts, and corpora albicantia in all the patients; graafian follicles in a significant number of patients; current corpus luteum (1/32); and recent corpora lutea (3/32). |
Spinder et al. [39] | 26 Transgender men undergoing GAS | 9 age-matched cisgender women | Histologic | 9 to 36 months (mean: 18 months) | Normal primordial and developing follicles in all patients (26/26). Multicystic ovaries (18/26), collagenization of the tunica albuginea (25/26), diffuse stromal hyperplasia (21/26), luteinization of theca interna (18/26), luteinized stromal cells (7/26), presence of corpora lutea (4/26), and corpora albicantia (26/26). PCOM (18/26). |
Pache et al. [40] | 17 transgender men | 13 cisgender women | Histologic | 11 to 72 months (mean: 21) | Increase in macroscopic volume of the ovaries (11/29), thickened and collagenized ovarian cortex (28/29), primordial follicles (28/29), higher number of healthy antrals and atretic vs. control (27 ± 13 vs. 11 ± 5), healthy antral follicles (18/29), atretic follicles (29/29), theca interna hyperplasia (29/29), diffuse stromal hyperplasia (29/29), and luteinized stromal cells were organized in clusters (12/29). |
Chadha et al. [41] | 11 transgender men | 10 cisgender women | Histologic | 11 to 72 months (mean: 21) | Increased number of cystic follicles and atretic follicles, collagenized and thicker ovarian cortex, theca interna hyperplasia and luteinization of follicles, stromal hyperplasia accompanied by clusters of luteinized cells, and higher AR receptor expression in 11/11. |
Mueller et al. [42] | 45 transgender men | No control | Transvaginal ultrasonography | 24 months | No significant changes. |
Grynberg et al. [43] | 112 transgender men | No control | Histologic | 24 to 108 months (mean: 44) | Macroscopical enlargement (90/224 ovaries), stromal hyperplasia (112/112), PCOM (89/112), and strong correlation with mean ovarian volume and number of antral follicles. |
Ikeda et al. [44] | 11 transgender men | 10 cisgender women with gynecologic malignancies who did not receive HT. | Histologic | 17 to 164 months (mean: 70) | In transmen group, thicker ovarian cortex, more hyperplastic collagen, ovarian stromal hyperplasia and stromal luteinization, but similar number of primordial follicles and early stage (primary, preantral, and early antral) follicles in the two groups. Higher rate of atretic follicles in transmen group. |
Loverro et al. [45] | 12 transgender men | No control | Histologic | Mean: 32 months | Multifollicular ovaries (10/12) and corpora lutea presence (2/12). |
Caanen et al. [46] | 56 transgender men | 80 cisgender women | 3D transvaginal ultrasonography | >12 months | No significant differences in PCOM between transmen group (17/53—32.1%) and control group (23/75—30.7%). |
De Roo et al. [47] | 40 transgender men | No control | Histologic, in vitro maturation, and immunohistochemical | Mean: 14 months | 1313 COC retrieved from the medulla of 35 patients; primordial follicles 68.52%, 20.26% intermediate, and 10.74%primary follicles. After 48 h IVM, 34.30% metaphase II oocytes obtained, with 87.10% having a normal spindle structure. |
Khalifa et al. [48] | 27 transgender men; 5 prior undergoing bilateral oophorectomy | No control | Histologic | 24 patients received androgen from 19 to 288 months. | Bilateral cystic follicles (23/23) and higher follicular density. |
Borràs et al. [19] | 70 transgender men undergoing GAS after HT | No control | Preoperative transvaginal ultrasonography and AMH assessment, after surgery histologic evaluation. | Not available | Antral follicles (43/47), presence of dominant follicle or corpus luteum (0/47). Thickening of tunica albuginea and luteinization of stromal cells (68.6%). Negative correlation between testosterone levels and total antral follicles. |
Study ID | Population | Control | Assessment | Average Duration of HT Intake | Findings |
---|---|---|---|---|---|
Futterweit et al. [37] | 19 transgender men | 12 age-matched cisgender women | Histologic | 12 to 120 months (mean: 37 months) | Proliferative endometrium (12/19), inactive (7/19), and leiomyomata (4/19). |
Miller et al. [38] | 32 transgender men | 36 cisgender women | Histologic | 12 to 96 months | Inactive endometrium (26/32), atrophic (6/32), and leiomyomata (5/32). Cervical mucosa atrophy (24/32) and focal interstitial eosinophilic infiltration (9/32) |
Chadha et al. [41] | 11 transgender men | 10 cisgender women | Histologic and immunohistochemical | 11 to 72 months (mean: 21) | Inactive endometrium (67% of samples), atrophic (33% of samples), and proliferative/active endometrium (0% of samples). AR expression more pronounced in myometrial and endometrial stroma in transmen group vs. control. |
Mueller et al. [42] | 45 transgender men | No control | Transvaginal ultrasonography | 24 months | Lower endometrial thickness. |
Perrone et al. [49] | 27 transgender men | 43 cisgender women, 13 fertile age, and 30 menopause | Histologic | 12 to 72 months (mean: 34 months) | Inactive endometrium (27/27) and nonfunctional polyps (5/27). Ki67 expression in transmen group similar to the menopausal group; both lower than fertile women group. |
Grynberg et al. [43] | 112 transgender men | No control | Histologic | 24 to 108 months (mean: 44) | Proliferative endometrium (54/112), atrophic endometrium (50/112), and leiomyomata (19/112). |
Loverro et al. [45] | 12 transgender men | No control | Histologic | Mean: 32 months | Proliferative endometrium (10/12), secretory endometrium (2/12), myometrial fibrosis (5/12), myometrial hypertrophy (2/12), and normal myometrium (5/12). |
Khalifa et al. [48] | 27 transgender men; 5 prior undergoing bilateral oophorectomy | No control | Histologic | 24 patients received androgen from 19 to 288 months | Proliferative endometrium (5/27), secretory endometrium (2/27), inactive endometrial glands (20/27), and focal decidua-like endometrial stromal change (16/27); cervical metaplasia (ectocervical or in zone of transformation—17/27). |
Grimstad et al. [50] | 94 transgender men | No control | Histologic | 0 to 12 months (22/94), >12 to 24 months (30/94), >24 to 48 months (19/94), and >48 months (23/94) Mean: 36.7 ± 36.6 months | Proliferative endometrium (61/94), atrophic endometrium (23/94), secretory endometrium (4/94), endometrial polyps/myomas (9/94), adenomyosis (7/94), complex hyperplasia without atypia (1/94), and other benign disease (4/94). |
Hawkins et al. [51] | 81 transgender men | No control | Histologic | Mean: 48 months (duration of preoperative HT noted only on 70 patients) | Proliferative endometrium (33/81), atrophic endometrium (40/81), endometrial polyps (9/81), and no cases of endometrial hyperplasia or malignancy. |
Asseler et al. [52] | 51 transgender men | 77 cisgender women | Transvaginal ultrasonography | Mean: 30.2 months | Significantly lower endometrial thickness in transmen group compared with cisgender women: median 3.9 mm (interquartile range [IQR] 2.8–5.1) and 4.9 mm (IQR 4.0–6.3), respectively (p < 0.001), after correcting for confounding factor. |
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D’Amato, A.; Cascardi, E.; Etrusco, A.; Laganà, A.S.; Schonauer, L.M.; Cazzato, G.; Vimercati, A.; Malvasi, A.; Damiani, G.R.; Di Naro, E.; et al. “Lights and Shades” of Fertility Preservation in Transgender Men Patients: A Clinical and Pathological Review. Life 2023, 13, 1312. https://doi.org/10.3390/life13061312
D’Amato A, Cascardi E, Etrusco A, Laganà AS, Schonauer LM, Cazzato G, Vimercati A, Malvasi A, Damiani GR, Di Naro E, et al. “Lights and Shades” of Fertility Preservation in Transgender Men Patients: A Clinical and Pathological Review. Life. 2023; 13(6):1312. https://doi.org/10.3390/life13061312
Chicago/Turabian StyleD’Amato, Antonio, Eliano Cascardi, Andrea Etrusco, Antonio Simone Laganà, Luca Maria Schonauer, Gerardo Cazzato, Antonella Vimercati, Antonio Malvasi, Gianluca Raffaello Damiani, Edoardo Di Naro, and et al. 2023. "“Lights and Shades” of Fertility Preservation in Transgender Men Patients: A Clinical and Pathological Review" Life 13, no. 6: 1312. https://doi.org/10.3390/life13061312