In the 1940s, doctors believed that a heterosexual couple’s infertility was due to mental issues. Specifically, it was due to the woman’s mental issues; for example, her “unconscious hatred towards [her] husband or fear of sexual intercourse”, might trigger an “adrenaline-like response in vaginal muscles leading to painful intercourse or expulsion of semen”. In other words, the woman’s mental state led to a physical response that prevented her husband’s sperm from reaching her egg and resulted in infertility.
In truth, infertility – which is defined as the failure to conceive after one year of having regular, unprotected intercourse and which affects one in six couples worldwide – is not due to the mental state of any one partner, no matter his or her sex. Rather, the root cause of infertility is fairly equally split between partners in a heterosexual relationship: one-third of infertility cases are due to female reproductive issues, one-third are due to male reproductive issues, and one-third are due to either the male and female reproductive issues together or from completely unknown causes.
And yet, as Dr. Piraye Yurttas Beim, Founder and CEO of Celmatix, explains, the burden of care for infertility is not equally split. One of the goals of Celmatix, a pre-clinical stage biotech company focused on women’s health, is to allow women not only to survive but also to thrive well past midlife. To do so, however, Dr. Beim notes society needs better fertility treatments – and a more equal approach to fertility – than it has.
One of the therapeutics that Dr. Beim and the Celmatix team is developing, an Oral Follicle Stimulating Hormone (FSH) Receptor Agonist, will help achieve those goals by increasing fertility in both women and men. For women, current injectables with FSH have already been shown to regulate ovulation, and as many as 50% of women who start to ovulate are able to become pregnant. For men, FSH injectables are already used in Europe to improve men’s sperm quality, and thus, fertility – but haven’t yet been utilized as a male infertility treatment in the United States. Celmatix is aiming to offer these benefits of FSH therapy for both women and men but in an oral form – a pill – rather than as an injectable to eliminate some of the challenges of the latter. For example, Celmatix’s oral form of FSH would potentially open the possibility for it to be prescribed through a women’s OB/GYN or a male’s GP rather than through a fertility specialist: visits to which can have a range of out of pocket costs.
Payor costs may be lowered through Celmatix’s pill as well. The dose of an oral FSH can be titrated more finely than injectable hormones can be; therefore, doses could be more personalized – that is, adjusted for each individual – than is possible today. Injectables don’t have the same flexibility, and hyper-response to them can lead to life-threatening conditions, like ovarian hyperstimulation syndrome. For those with health insurance, payors may get the majority of the emergency treatment costs, including hospitalizations, which can cost multiple thousands of dollars in total.
Plus, an oral fertility medication that can help both men and women democratizes infertility treatments. Currently, even male-based infertility is addressed through treatment processes such as in vitro fertilization (IVF): a treatment that requires dozens of needle injections – which 53% of adults fear and which women fear at a greater rate than men – and places the (physical) burden on the woman in the partnership: the one who has to receive the IVF treatments. As Dr. Beim notes, “I think men would be happy to take the burden off their female partners but aren’t educated enough to know that they can.”
Science, in contrast, has often perpetuated the opposite idea: that women shoulder the responsibility for infertility treatments. A 2006 literature review concluded that only one article, of 157 total on gender and reproductive health, targeted men; about a decade later, a study found 81% of federally-funded US clinics with family-planning services provided preconception care and education to women. Only 38% provided the same to men.
In the 1940s, meanwhile, outrightly blaming infertility on a woman’s mental state was a fairly common medical practice. Physicians, psychiatric and non-psychiatric alike, endorsed these “psychogenic infertility” diagnoses: the idea that infertility that resulted from conditions such as the female patient’s so-called belief that sex was dirty, doubt about her ability to be a good parent, fear of sexual intercourse, hatred of her husband, “neurotic loneliness”, repressed fear or hostility, resentment about her role in society, or stress. As medical writer Randi Hutter Epstein summarized in her article, “Emotions, Fertility, and the 1940s Women”, these diagnoses benefited the physicians; she writes, “when [physicians] couldn’t help a patient with their medical solutions, labeling the problem as a mental one helped minimize the number of undiagnosable cases in [the physicians’] statistical reporting.” A 2018 article adds that, due to the negative stigma around men’s infertility – from anxiety around semen analysis to connotations of impotence – women are still taking the blame for infertility, even today.
Women who are dealing with infertility already have “lasting trauma” in addition to this societal scapegoating: research has found they have depression and anxiety levels similar to individuals with cancer, H.I.V. and heart disease. Blaming them for infertility only increases this psychological stress along with anxiety, decreased self-esteem or and self-efficacy, depression, guilt, relationship problems, self-stigmatization, and stress. Up to 40% of women experiencing infertility have a psychiatric diagnosis, most often anxiety or depression, and may even have a physical condition too that prevents them from getting pregnant.
Celmatix’s second product helps treat some of these women: those with polycystic ovarian syndrome (PCOS). PCOS, a hormonal disorder that causes enlarged ovaries, affects an estimated 9% to 13% of women of reproductive age worldwide but 70% of cases go undiagnosed. The 30% who are diagnosed often need around two years and multiple doctors to receive the correct diagnosis.
PCOS is also one of the most common female causes of infertility, but, currently, there are no first-line treatments that actually address this health condition. Instead, treatment options, like lifestyle management, focus on managing symptoms, including mood swings, unwanted hair, and weight gain. Celmatix’s product in development, a novel melatonin receptor agonist, will be that first-line – and first of its kind – disease-modifying treatment for women with PCOS.
With Celmatix’s melatonin receptor agonist, women with PCOS would potentially be able to manage their fertility before it even becomes a potential issue. In other words, they can move from reactive care (waiting until an issue arises) to proactive care (managing fertility before an issue arises). “We’re increasingly thinking ahead to manage fertility,” Dr. Beim said, “I think the future of fertility is proactive management.”
Celmatix is providing that proactive management by addressing some of the biological causes of infertility for both women and men. In the process, the team is also reinforcing the ideas that infertility is not just a woman’s issue and that infertility treatments should not be limited only to women. Instead, those treatments – as well as the blame for and the burden of infertility – should be extended to both sexes in a way that psychogenetic diagnoses, like subconscious spousal hatred or fear of intercourse, never were.
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