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For transgender patients and providers, fertility preservation options bring choices, concerns

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Transgender patients visiting an endocrinologist to discuss the initiation of cross-sex hormone therapy are doing so during a period of newly increased awareness and advocacy. Today, gender incongruence is no longer considered a mental health disorder, and professional societies have outlined standards of care for transgender individuals that support increased access to gender-affirming HT.

But as more transgender patients are accessing necessary interventions — and gender transitions are initiated at younger ages — new questions are arising. The loss of fertility, which may occur as an unintended consequence of HT, can now be prevented. Available options for patients, which include oocyte and sperm cryopreservation, are increasingly more common and accessible. The changes are forcing new conversations for transgender health care providers, many of whom are struggling to keep up with a rapidly changing field.

Providers should bring up fertility preservation with patients or their parents as soon as medical intervention is considered, according to Courtney Finlayson, MD. Source: Craig Finlayson. Printed with permission.

“Fertility treatments have exploded and allowed for a better awareness of this issue,” Sheryl Kingsberg, PhD, chief of the division of behavioral medicine in obstetrics and gynecology at University Hospitals Cleveland Medical Center, and a professor in reproductive biology and psychiatry at Case Western Reserve University School of Medicine, told Endocrine Today. “[Losing your fertility] used to be considered the price you pay for transitioning. That no longer is a required price.”

Many transgender patients remain unaware of their fertility preservation and reproductive options, according to experts. Many providers have not received proper training regarding transgender fertility counseling, which is now formally recommended by the Endocrine Society before beginning any HT.

“In the medical community, there is a growing awareness about this, but a lot of work still needs to be done,” Courtney Finlayson, MD, endocrinologist for the Gender and Sex Development Program at Ann and Robert H. Lurie Children’s Hospital of Chicago, told Endocrine Today. “In the recent Endocrine Society guidelines on transgender care, there are recommendations that, before every type of medical intervention, fertility preservation should be discussed. That is new. In the trans community, there is a growing awareness regarding options for fertility preservation, but, from what we see so far in the research, patients have a limited understanding of their specific fertility preservation options.”

Sheryl Kingsberg

In a survey of transgender individuals conducted in Toronto, presented at the Endocrine Society’s 2017 annual meeting, data showed nearly one-fourth of transgender adults regarded their own fertility as important; however, most cited a lack of knowledge regarding reproductive options. Within the cohort of 213 adults, only 3% reported banking sperm or eggs before beginning HT, and 77% reported never discussing fertility preservation with a health care provider. The most commonly reported barriers to fertility preservation cited were cost (41%), lack of awareness of options (21.6%) and not wanting to delay HT (19.7%).

“There still is not enough awareness about this,” said Kingsberg, who formerly chaired a postgraduate course for the American Society for Reproductive Medicine on transgender fertility. “The whole concept of transgender as an identity has grown, in large part due to social media and availability of the internet. Although it is now a common topic to discuss, the prevalence remains low, and a lot of transgender individuals were isolated for a long time.”

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Starting the conversation

The most recent edition of the Standards of Care produced by the World Professional Association for Transgender Health (WPATH), published in 2011, advises that health care professionals — including mental health professionals recommending HT or surgery, hormone-prescribing physicians and surgeons — discuss reproductive options with transgender patients before initiating medical treatments for gender dysphoria.

“These discussions should occur even if patients are not interested in these issues at the time of treatment, which may be more common for younger patients,” the guideline states.

Lisa Campo-Engelstein

Any decisions regarding fertility are fraught with additional complicating factors for transgender patients, according to experts. A transgender man opting to freeze oocytes, for example, should also consider the potential distress that may come with discontinuing HT to later carry a pregnancy, the cost and burden of in vitro fertilization for either the patient or a potential partner, or the difficulty and cost involved in selecting a surrogate. Providers must confront a host of additional issues regarding how best to proceed with transgender adolescents, particularly those who have yet to begin puberty.

“It needs to be brought up early,” Lisa Campo-Engelstein, PhD, an associate professor at the Alden March Bioethics Institute at Albany Medical College who specializes in reproductive ethics, told Endocrine Today. “Historically, reproduction has been relegated to an elective area of medicine. We see that even in oncology with cancer patients. The same thing happens with transgender care. We want to treat what you are coming in for, which is gender-affirming treatment. That is what is most important. Fertility preservation is on the back burner.”

The key, Campo-Engelstein said, is to move the issue of fertility to the “front burner” for transgender patients — and to discuss options not just early, but often.

“For many people, biological children are hugely important, and [losing that option] is a side effect of hormone treatment that is irreversible,” said Campo-Engelstein, also the co-editor of Reproductive Ethics: New Challenges and Conversations. “Patients need to know about their options, and they need to have the discussion more than once. Transgender youth are so eager to start treatment, that they may not think twice about how these treatments can affect their fertility.”

Finlayson said patients, particularly pediatric patients, need time to absorb the complexity of the issue.

“What happens is people start talking about this right before a person wants to start estrogen or testosterone, and it can put pressure on the decision, and delaying gender-affirming hormones can be a deterrent to fertility preservation,” Finlayson said. “This should be discussed as early as you start talking about medical intervention. I start talking about it even with fairly young kids, if we’re talking about pubertal suppression. Usually I bring it up in the context of discussing side effects of medication.”

Teresa K. Woodruff, PhD, the Watkins Professor of Obstetrics and Gynecology at Northwestern University’s Feinberg School of Medicine and founder and director of the global Oncofertility Consortium, also saw similarities between patients with cancer and transgender individuals who seek fertility preservation. Woodruff, who coined the term “oncofertility” in 2006 to describe the merging of oncology and reproductive medicine, has now expanded the reach of the consortium to include transgender fertility concerns.

“The cancer patient is not able to wait for eventual sterility before they can act,” Woodruff told Endocrine Today. “The Oncofertility Consortium provides that a priori discussion about fertility in the setting of iatrogenic treatments. Over time, patients who had disorders of sex determination, as well as pediatricians managing transgender youths, in particular, began to think about what the future fertility concerns would be for their patients. That represented a starting point for this larger exploration, which has been fascinating.”

Woodruff said an ideal conversation will involve the family unit in addition to the patient — some of whom may have conflicting views on the matter.

“At some level, even though this is a conversation that some parents and guardians are interested in, the individuals themselves can sometimes be conflicted regarding the biological origin of gametes,” Woodruff said. “For someone transitioning between sexes, that decision can be fraught. So, there is a much broader conversation here that we hope is happening. It depends on the individual, their age and their family circumstances.”

Cost is also an important consideration that should be discussed, according to Maurice Garcia, MD, MAS, associate professor of urology and director of the Transgender Surgery and Health Program at Cedars-Sinai Medical Center in Los Angeles.

“Providers who offer these surgeries should be familiar, roughly, with how much it costs to freeze sperm,” Garcia, who has specialized in gender-affirming surgery for 5 years, told Endocrine Today. “Once you’ve frozen your cells, you have to maintain them. For sperm banking, it’s around $1,000 to $1,300 initially, and between $150 to $200 a year to store. For transgender men, freezing eggs costs more because the process requires hormones and a procedure to harvest the eggs. Transgender couples can be opposite and same sex and so have use for in vitro fertilization. In vitro fertilization can cost anywhere from $15,000 to $30,000 a try, and that often is not covered by insurance. ... Also, none of it is guaranteed. It’s not fair to talk to someone about risks and then not give them any sense of what’s around the corner.”

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Fertility preservation options

The 2017 Clinical Practice Guideline published by the Endocrine Society states that techniques for cryopreservation of oocytes, embryos and ovarian tissue continue to improve, and oocyte maturation of immature tissue is being studied. For natal males with gender incongruence in a later phase of puberty or adulthood who wish to begin HT, spermatogenesis is sufficient for cryopreservation and storage of sperm. In vitro spermatogenesis is currently under investigation. Restoration of spermatogenesis after prolonged estrogen treatment has not been studied.

Maurice Garcia

For natal females with gender incongruence, the effect of prolonged treatment with exogenous testosterone on ovarian function is uncertain, according to the guideline.

Options for adolescents in early puberty are limited. Treating early pubertal youths with gonadotropin-releasing hormone (GnRH) analogues, for example, will temporarily impair spermatogenesis and oocyte maturation, the guideline states, and delaying or temporarily discontinuing GnRH analogues to promote gamete maturation is an option, but one that is often not preferred.

“This is where it becomes challenging,” Finlayson said. “One option would be to go off the pubertal blocker, but then the patient would have to allow enough puberty to occur to retrieve mature eggs or sperm. That’s a lot of puberty. That’s going to introduce the secondary sex characteristics that they were likely trying to prevent with the blocker. So, we present that as an option, but I have never had a patient choose to do that.

“We are hoping that we will be able to offer gonadal cryopreservation options, just like they do with oncology patients,” Finlayson said. “I don’t think anyone is currently offering that in the transgender population. But likely within 10 years, that is going to be different. I hope that the options will be so much better.”

For transgender men who have initiated HT and wish to carry a pregnancy, either with a biological preserved oocyte or donated material, there is little guidance available regarding when to stop or restart testosterone therapy.

“There is just not a lot of data,” Garcia said. “There are not evidence-based guidelines regarding when to get off testosterone [to become pregnant]. If you’re on testosterone, it is affecting the complex interplay of hormones that support pregnancy in someone with ovaries. I’ve talked to colleagues who have suggested that a reasonable amount of time to be off hormones is 6 to 9 months before attempting pregnancy. It can vary. Whoever a patient sees for this will follow their hormone levels, and it could take less or more time before the pituitary axis gets back to ‘normal’ to be ready for pregnancy.

“I tell patients, ‘I can’t give you black and white answers. It’s something you must see for yourself,’” Garcia said. “But I always tell them they need to find a fertility specialist they trust because they will be working with that person closely.”

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An unintended consequence

Patricia Robertson, MD, a maternal fetal medicine specialist with UCSF Women’s Health, recalled a recent transgender male patient in her care who said a provider told him he could not become pregnant while taking testosterone.

“He had a 20-lb weight gain and went to one clinic, where he was told he had an ovarian cyst,” Robertson said. “And then he went to another one and found out he was 30 weeks pregnant.”

Although initially shocked, the patient went through with the pregnancy and had a healthy baby, Robertson said, but the care team confronted several issues. The patient, for example, wanted a caesarean section to avoid any distress related to a vaginal birth.

“I didn’t want that for him because it’s higher risk,” Robertson said. “But, I sent him to our psychiatrist for her opinion, and she felt a vaginal birth could be harmful to him because he was early in his transition, and this would exacerbate his gender dysphoria. She recommended a [caesarean] section. He only had 10 weeks to transition from thinking he wasn’t pregnant to becoming a dad. We restarted him on testosterone at about 3 weeks [after the birth].”

Teresa Woodruff

Health care providers must inform transgender men taking testosterone that they can become pregnant and must use contraception if they want to avoid pregnancy, Robertson said.

Woodruff also underlined the importance of discussing contraception when going over fertility preservation options with patients.

“Just as in a cancer setting, we often think about sterilization as the outcome, but an unintended consequence can be pregnancy,” Woodruff said. “We should be talking about this from the male and female perspective. As we’re moving beyond the cancer tent to those individuals who are transitioning, the bottom line is, in these cases, we must think about these individuals as being sexual. Talking about hormonal contraception or barrier contraception is important for their overall health. The broader context is to always consider a conversation about contraception, particularly for young people.”

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Creating a positive experience

As awareness about transgender health in general grows, Robertson said it is important for providers to create a welcoming atmosphere for patients. Things that may seem small, like a rainbow triangle posted outside the office, can convey a message of understanding to a marginalized patient population, opening the door wider for discussions about complex issues like fertility.

“Whenever my young man would come in, he couldn’t use his preferred name because of issues with the electronic medical records,” Robertson said. “That’s important. This is a tiny population ... but they have the worst health outcomes of everyone under the LGBT umbrella, in terms of violence suffered, depression, unemployment. They are going to be attuned to how welcoming the office is.”

The importance of a broad care team participating in shared decision-making regarding any fertility preservation measures is also important, Campo-Engelstein said.

“I’m working on a project right now where we are interviewing transgender individuals about their experiences with health care providers, and it was horrifying to me to see how many trans patients felt their doctors were judging them,” Campo-Engelstein said. “I don’t think it was necessarily intentional. It is important to be open and respectful, which seems like an obvious message. Patients also need to have an interdisciplinary team. This is a complex issue. You need the behavioral scientist, the psychologist. You might need an ethicist. You might need a reproductive endocrinologist. This can be emotionally challenging, so I would also recommend support groups. Sometimes talking to others who have gone through this can be helpful to the patient.”

Woodruff said an optimal experience for transgender patients can be achieved when the conversation around fertility preservation is part of the standard of care in every office.

“In the cancer world, we say oncofertility should be considered the same way we would consider a referral to plastic surgery or to reconstruction or to genetics,” Woodruff said. “If this is just part of the referral network, then it doesn’t seem odd.”

Additionally, Robertson said, providers should “keep an open mind” about what transgender patients may need or want, which can vary widely from person to person.

“Many transgender people do not undergo bottom surgery,” Robertson said. “You have to keep track of what testing needs to be done, if, for example, a transgender man still has a uterus. Most transgendered people prefer not to have to teach their health care providers about trans health, but until provider education is improved, that is what is happening.” – by Regina Schaffer

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References:

Hembree WC, et al. J Clin Endocrinol Metab. 2017;doi:10.1210/jc.2017-01658.

Kim BH, et al. Abstract #SUN110. Fertility among people of transgender experience. Presented at: ENDO 2017; April 1-4, 2017; Orlando, Fla.

The Oncofertility Consortium. Available at: www.oncofertility.northwestern.edu/. Accessed Jan. 10, 2018.

World Professional Association for Transgender Health. Standards of Care, Version 7. Available at: www.wpath.org/site_page.cfm?pk_association_webpage_menu=1351. Accessed Jan. 11, 2018.

For more information:

Lisa Campo-Engelstein, PhD, can be reached at the Alden March Bioethics Institute at Albany Medical College, 47 New Scotland Ave., Albany, NY 12208; email: campoel@amc.edu.

can be reached at the Alden March Bioethics Institute at Albany Medical College, 47 New Scotland Ave., Albany, NY 12208; email: campoel@amc.edu. Courtney Finlayson, MD, can be reached at the Ann and Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave., Box 54, Chicago, Il 60611; email: cfinlayson@luriechildrens.org.

can be reached at the Ann and Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave., Box 54, Chicago, Il 60611; email: cfinlayson@luriechildrens.org. Maurice Garcia, MD, MAS, can be reached at Cedars-Sinai Medical Center, 8635 W. Third St., Suite 1070W, Los Angeles, CA 90048; email: maurice.garcia@cshs.org.

can be reached at Cedars-Sinai Medical Center, 8635 W. Third St., Suite 1070W, Los Angeles, CA 90048; email: maurice.garcia@cshs.org. Sheryl Kingsberg, PhD, can be reached at MacDonald Women’s Hospital, Mailstop 5034, 11100 Euclid Ave., Cleveland, OH 44106; email: sheryl.kingsberg@uhhospitals.org.

can be reached at MacDonald Women’s Hospital, Mailstop 5034, 11100 Euclid Ave., Cleveland, OH 44106; email: sheryl.kingsberg@uhhospitals.org. Patricia Robertson, MD, can be reached at UCSF Medical Center, 505 Parnassus Ave., San Francisco, CA 94143; email: patricia.robertson@ucsf.edu.

can be reached at UCSF Medical Center, 505 Parnassus Ave., San Francisco, CA 94143; email: patricia.robertson@ucsf.edu. Teresa Woodruff, PhD, can be reached at Northwestern University Feinberg School of Medicine, 420 E. Superior St., Chicago, Il 60611; email: tkw@northwestern.edu.

Disclosures: Garcia reports he is a consultant for American Medical Systems, Coloplast and Pfizer and is the owner of MLM Medicus, LLC, and Safe Medical Designs, LLC. Woodruff is director of the Oncofertility Consortium at Northwestern University. Campo-Engelstein, Finlayson, Kingsberg and Robertson report no relevant financial disclosures.