First Childbirth after Fertility Preservation and Gender Reassigning Surgery from Indian Transgender Community

Abstract

Fertility preservation (FP) is critical for those members of the transgender community who desire biological offspring in the future. As gender-affirming hormone therapy and gender-affirming surgeries (GASs) negatively affect future fertility potential, awareness amongst care providers and the transgender population regarding FP and family-building options is the need of the hour. As the first case of childbirth after transgender FP and GAS in India, this will be a beacon of hope for transgender family-building options in India.

INTRODUCTION

The transgender community is an underserved population, from reproductive to fertility aspects. Of particular concern is the poor utilisation of fertility preservation (FP) services, as gender-affirming hormone therapy (GAHT) may negatively affect future fertility potential. Moreover, gender-affirming surgeries (GASs) usually lead to permanent sterility in these patients. Even though the desire for biological parenthood in transgender individuals ranges from 13% to 54%,[1,2] the percentage of people accessing FP options is negligible. Gaining access to FP counselling may be harder for transgender people compared to cisgender individuals, for various reasons including non-availability of services or knowledgeable people in the healthcare sector, cultural and social bias of healthcare providers, financial barriers and lack of support from own families.[3] The ability to biologically parent a child can be, especially complicated in transgenders, as a result of hormonal treatments, surgeries or not having the biological means to become a parent using ‘traditional’ methods. ESHRE FP guidelines[4] and ASRM committee[5] emphasise the need for FP counselling before gender reassigning therapies.

According to the latest data available, as per the 2011 census,[6] 0.49 million people have been identified as transgenders, in India. As the number of gender-affirming surgeries in the world is increasing,[7] the need for more structured and comprehensive FP options is also essential. In India, currently, no data is available regarding the percentage of transgenders who wish to preserve their gametes or wish to pursue parenthood. This, being the first reported case of attaining biological parenthood after gender-reassigning surgeries in India will be a beacon of hope for our transgender brethren who want to have their biological progeny, employing FP.

CASE REPORT

Access to FP options in India is currently limited, due to the lack of awareness amongst the transgender population, healthcare providers, discrimination at multiple levels of the healthcare system, the sheer cost of treatment and the lack of adequate legal support. Our core goal was to address existing gaps in the healthcare system by offering compassionate and comprehensive FP services to the transgender community.

The index case was that of a transman aged 29 years, who approached the fertility unit of a multi-speciality hospital, enquiring about the possibility of biological parenthood after gender assigning treatments. The patient had not started on gender reassigning treatments, at this point. The transman was accompanied by the cisgender female partner and various options of family building such as, (1) doing embryo transfer in the transman itself after GAHT and acquiring desired physical attributes, (2) Doing embryo transfer in the cisgender female partner after a legal marriage (co-in vitro fertilisation [IVF]) and (3) Doing embryo transfer using cis female partner’s oocytes and donor sperm after a legal marriage, were discussed. Transman and his cis female partner wanted to proceed with cryopreserving the embryos using transman’s oocytes and donor sperm and transferring it to the cis female partner after marriage. Legal advice was sought, as we could not find any similar case in India, and affirmative confirmation was received regarding FP and the possibility of transferring embryos to a legally married partner. As per the legal advice, since FP is the basic right of the individual regardless of age and gender orientation, and after legal marriage, transman and cis female partner are eligible for all rights assigned to the heterosexual couple in the country, we can proceed with the planned procedures. We proceeded with pre-IVF evaluation after having detailed counselling about the process of ovarian hyperstimulation, which includes vaginal bleeding, transvaginal ultrasonography (USG), possible estrogenic symptoms due to raised hormonal levels and possible distressing symptoms because of the vaginal manipulations including oocyte aspiration. Transman’s ovarian reserve was within normal limits expected for the age, with regular cycles, an anti-Mullerian hormone of 2.75 ng/dL and antral follicle count of 18. Transman was induced bleeding with norethisterone acetate 5 mg twice daily for 5 days. On the second day of bleeding, recombinant follicular stimulating hormone (FSH) was started at 200 IU once a day along with tablet letrozole 2.5 mg once daily at night-time. Started on gonadotropin releasing hormone (GNRH) antagonist 0.25 mg on d5 of stimulation once the lead follicle was 14 mm. A dual trigger, with 250 µg of recombinant human chorionic gonadotropin and GNRH agonist 0.4 mg, was given when the lead follicle was 18 mm. Oocyte pickup was done 34.5 h later, using Cook’s single-lumen 17F needle. 9 mature oocytes were obtained from 15 cumulus oocyte complex aspirated. Intracytoplasmic sperm injection (ICSI) with donor sperm was performed in 9 mature oocytes and 8 D2 embryos were frozen. During the process of ovarian stimulation and oocyte retrieval, transman had gender dysphoric symptoms, especially at the time of transvaginal ultrasounds which was managed by detailed counselling sessions and a compassionate approach from the whole team in our reproductive medicine unit. Transman underwent GASs and hormone therapy as per WPATH[8] protocol. After acquiring the legal status of male gender as reflected in his AADHAR card and got legally married to a cis female partner. The cis female partner was evaluated before embryo transfer and was found to have a submucous fibroid which was removed by hysterolaparoscopy. Endometrial preparation was done by modified natural cycle and 2 D3 (D2 embryos were thawed and cultured to D3) embryos were transferred using a Cooks Guardia sure view catheter. Pregnancy was confirmed by a beta-HCG assessment after 12 days of embryo transfer, continued uneventfully till term and delivered a 2.8 kg healthy male baby by lower segment cesarean section (LSCS).

DISCUSSION

The current FP options available for transgender men are 1) oocyte cryopreservation, 2) embryo cryopreservation after IVF or ICSI with partner’s or donor sperm and 3) Ovarian tissue cryopreservation with or without in vitro maturation (IVM).

Oocyte and embryo cryopreservation are widely available in all fertility centres where IVF is being practised and can be performed before or after starting hormone replacement therapy.[9,10] A case report by Wallace et al. describes the first case of transgender male undergoing oocyte cryopreservation before starting masculinising hormone therapy.[11] There is no clear consensus on the effects of androgen therapy on the ovarian reserve or fertility outcome or the timing of ovarian stimulation after suspending the hormone therapy.[12,13,14] Various studies proposed a time gap of 3–6 months while a case report of two transmen undergoing ovarian stimulation without suspension of GAT[15] was also published. After controlled ovarian hyperstimulation, the oocytes obtained can be cryopreserved for the future, or fertilised with donor sperm or sperm from the partner depending on the options preferable for the patient. The embryos can be frozen or freshly transferred to the surrogate or female cis partner or the patient itself depending on the patient’s preference and laws prevailing in the country.

Ovarian tissue cryopreservation (OTC) is generally performed by laparoscopy under general anaesthesia, excising a part or whole of the ovary and keeping cryopreserved for future use. The tissue can be thawed and reimplanted into the patient’s body and stimulated to produce mature oocytes later. The advantages compared to oocyte or embryo cryopreservation are, that it does not have the need to stop the hormone therapy, it can be done in the same sitting as GAS, and it is the only option available in the pre-pubertal age group. Freezing can be done by slow freezing or vitrification.[16] Even though there is a lack of data in transgender population, it has been used in success with cancer patients and pre-mature insufficiency patients.[17,18,19]

Oocytes at different stages of maturation are retrieved from the surgically removed ovarian tissue and cultured in vitro and fertilised through ICSI. This could be an option to avoid negative features following tissue re-transplantation after OTC, such as the need for a second intervention carried out under general anaesthesia, interruption of hormone therapy and multiple vaginal ultrasound requirements for COS.[20,21] However, with the current studies available, we cannot recommend it for routine use in the transgender population.[22]

Number of oocytes retrieved and maturity of oocytes in transgender males are comparable with cisgender females undergoing oocyte cryopreservation.[23] The total dose of gonadotropins used was higher in the transgender group in the study by Leung et al.[24] The authors ascribe it to the more aggressive stimulation as it is a ‘one shot deal’. Regarding the FP outcome after OTC/IVM in the available literature is not enough to recommend it as a standard procedure. A study by Christodoulaki et al.[25] suggested spindle cell transfer to attain similar blastulation rates in transgender patients compared to cisgender patients.

One study,[26] which is a case report says, of three transgender men who underwent FP two had transferred the embryo to cisgender partners and delivered. The study by Leung et al. reported 16 transgender men undergoing oocyte cryopreservation and seven doing embryo transfer in their cisgender partners, all achieving live births. Another study[27] by A. Ghofranian et al. describes the experience of 81 couples, with at least one of them identify as transgender, reported to a single centre for fertility treatments. Of the 141 planned cycles, 106 progressed to fertility treatment. Twelve live births were achieved from 15 IVF and co-IVF cycles. One live birth and seven ongoing pregnancies were reported from 76 intrauterine insemination cycles.

A case report[28] of a 26-year-old transman, who was on testosterone therapy for 4 years, undergoing FP and co-IVF describes aggressive stimulation with recombinant follitropin alpha 450 units and lutropin alpha 150 units for 10 days and triggered with leuprolide acetate. They had retrieved 56 COCs of which 29 mature oocytes were there. Another case report[29] from the same centre where a transman, 20 years old, who was on testosterone therapy for 18 months, was stimulated with recombinant follitropin alpha 175 units and lutropin 75 units. The trigger used was leuprolide acetate 3 mg on the 9^th day of stimulation followed by retrieval of 25 COC, and 22 mature oocytes were obtained. The ability of the pituitary to mount a physiological response after prolonged testosterone exposure is questioned in both cases, where there was a rise in LH 12-h post-trigger as noted in both cases and retrieval of mature oocytes. GNRH agonist trigger is ideal in such cases for rapid luteolysis and to reduce the risk of OHSS.

Young age, testosterone exposure and aggressive stimulation may be contributing to the robust response in these cases. Mild stimulation is another approach that can be considered in transman ovarian stimulation to reduce the oestrogenic symptoms and incidence of OHSS. This again points towards the need for guidelines for transman ovarian stimulation who are on various stages of gender-assigning treatments. Continuous testosterone administration and the use of aromatase inhibitors during ovarian stimulation may potentially reduce the distressing effects of hormonal ovulation induction[30] without affecting the outcomes which again needs to be confirmed in further studies.

Embryo cryopreservation is a method that has been in practice for a longer period, whereas oocyte cryopreservation attained the status of ‘no longer an experimental treatment’ after ASRM 2013.[31] Embryo survival is >95%[32] for vitrified blastocysts compared to 80%–90% for vitrified oocytes.[33,34] But when the clinical outcome of fresh and frozen oocytes was compared, there was no significant difference in fertilisation rates (80.7% vs. 78.2%) and clinical pregnancy rates (40.8% vs. 33.3%).[35] The advantage of oocyte freezing usually suggested is the maintenance of reproductive autonomy. In transman FP, if the partner is a cisgender female, the need for donor sperm is obvious. But in the event of a change in the partner to a transgender female who has not undergone GRS where the availability of the partners sperm will be there, embryo cryopreservation limits the possibility of having biological parenthood for both partners at the same time. This must be included in the counselling for FP if the transman is opting for the cryopreservation of the embryo using donor sperm. Counselling regarding the success rates in terms of clinical pregnancy rates and live birth rates based on age, AMH and co-existing conditions which affect ovarian response also needs to be included.[36,37] Setting realistic expectations regarding the number of cryopreserved oocytes as well as the number of planned oocyte cryopreservation cycles needed to achieve the goals, particularly in older individuals is to be discussed in detail.[38]

FP journey can worsen gender dysphoria in transgender people and can be emotionally and psychologically draining. Therefore, efforts should be made to include counselling in all stages of FP to alleviate anxiety and pain. This includes creating a compassionate and inclusive atmosphere in the fertility clinic and establishing a non-discriminatory and gender-neutral policy.[39] Fertility clinics should provide gender-free bathrooms and documentation with appropriate pronouns.[39]

In India, FP options for transgender people are still in the infantile stage. No literature is available regarding the family-building aspirations of transgender people or the number of transgender people who have undergone any kind of FP previously. FP for transgender females, especially before starting GAHT is much more technically simple, widely available and less costly. However, we could not find any reported case of FP in transwomen in the Indian scenario.

In our hospital, two more transgender men have done their embryo cryopreservation before gender assigning procedures and many enquiries are coming about the transgender family-building options. Our three patients had done FP before starting their GAHT. More people coming ahead for FP from the transmen category before and after the initiation of testosterone therapy will only provide more insight to make an optimal protocol for FP along with GAHT, as GAHT is primarily done by endocrinologists.

CONCLUSION

The first reported case of childbirth through FP after gender-reaffirming surgeries could be a guiding way to more transgender people coming ahead for the dream of their biological parenthood. More people doing FP only will bring out more studies on the effect of GAHT on ovarian response, the optimal time duration of discontinuation of GAHT, if needed and various family-building options possible in the legal framework of India. Preserving the uterus in patients who are on long-term testosterone also needs to be evaluated. Further studies in the Indian context are needed to make an optimal protocol. Moreover, it is very evident that a multidisciplinary approach is essential for comprehensive FP in transgender patients. Collaboration between endocrinologists, reproductive specialists, legal experts and mental health specialists is crucial to address the complex needs and concerns of this group of patients. Close follow-up of children growing up in these families is also an essential part to make the family-building guidelines in India.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Author’s contribution

All authors were involved in the writing and editing of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author, upon reasonable request.