Infertility rates among the pemphigus population.

The impact of pemphigus on male and female infertility is unknown. Infertility affects up to 15% of couples and counseling patients on impact on fertility when given a new medical diagnosis is an important part of medical care. 1 In women, the diagnosis of pemphigus tends to occur at a time when fertility is rapidly declining, making this information even more important. One prior case series described 9 patients with pemphigus vulgaris, 8 of whom were unable to become pregnant. 2 Our goal was to further determine rates of infertility in patients with pemphigus.

The authors confirm that any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies.

SAK and BS developed the study and wrote the manuscript. AH was a subspecialty contributor to manuscript development. DRP assisted with methodology and design. RF provided statistical analysis.

Supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.

A retrospective chart review was performed for patients of reproductive age (ages 15–49) with a diagnosis of pemphigus vulgaris or foliaceus, as confirmed by laboratory testing or clinician assessment, at the University of Minnesota MHealth Dermatology Clinic from 2005 to 2019. Each chart was assessed for diagnosis or mention of infertility via chart review and included review of obstetric/gynecology, primary care, and endocrinology notes as well as utilization of the keyword search function for “infertility.” Mutually exclusive groups were defined as “definite infertility” (DI; meeting criteria as per obstetrician/ynecologist clinician assessment and/or formal infertility definition), “reproductive issues” (RI; infertility or recurrent pregnancy loss discussed in any clinician notes, though the diagnosis was not confirmed by clinician and/or infertility definition), and having a “diagnosis associated with infertility” (DAI) as is listed in Table 1 . We assessed all the above groups so as not to miss an association with pemphigus and infertility. Patients with pemphigus were compared to age- and sex- matched control patients who had been evaluated in our general dermatology clinic without a diagnosis of pemphigus. We then compared controls to those with DI as well as to those with those RI and DAI using Fisher’s exact tests. Measures assessed included demographics, rates of infertility, and for patients who met criteria for infertility, the severity of their pemphigus, associated comorbidities, and medications taken. Demographic characteristics of pemphigus versus control patients Chemotherapy associated with infertility searched and/or extracted from notes (not including cyclophosphamide) were ifosfamide, chlorambucil, cisplatin, procarbazine, busulfan, methotrexate, trastuzumab, doxorubicin, paclitaxel, pembrolizumab, ipilimumab, systemic 5-fluorouracil. Meeting criteria as per obstetrician/gynecologist clinician assessment and/or formal infertility definition. Infertility or recurrent pregnancy loss discussed in any clinician notes, though the diagnosis was not confirmed by obstetrician/gynecologist clinician and/or meeting criteria of formal infertility definition. Obstetric, gynecologic, and endocrine conditions associated with infertility which were extracted from notes included polycystic ovarian syndrome, endometriosis, uterine polyps/fibroids, pelvic inflammatory disease, recurrent bacterial vaginosis, abnormal uterine bleeding, ovarian torsion, mumps, and undescended testes.

Of 46 patients of reproductive age with pemphigus, 3 (6.5%) had DI, 3 (6.5%) had RI, and 6 (13.0%) had DAI (Table 1 ). Two patients with either RI or a DAI had vaginal involvement of their pemphigus; no patients with DI had genitourinary involvement (Table 2 ). Demographic information collected for pemphigus patients with and without fertility were similar. Compared to patients with pemphigus and no fertility issues, patients with DI and RI did not have more severe disease as assessed by rates of hospitalizations and desmoglein titers. Rates of rituximab usage were similar. No patients with pemphigus had received cyclophosphamide. Compared to controls, there was no statistically significant difference in rates of infertility in patients with DI ( P = 1.0; 4.3% controls vs 6.5% pemphigus), in patients with DI and RI ( P = .739; 8.7% vs 13.0%), or in patients with DI, RI, and DAI ( P = .052; 8.7% vs 26.1%). Demographic characteristics of pemphigus patients with and without infertility

Infertility rates in patients with pemphigus do not appear increased relative to the general dermatology population, even when considering patients with possible RI and DAI. This information can aid in counseling patients of reproductive age diagnosed with this condition. Larger prospective studies are needed to confirm these findings. This was a single-center, retrospective chart review at an institution without a dedicated Reproductive Endocrinology and Infertility clinic, which may underestimate rates of infertility. Although the rates of infertility approached significance when including RI, and DAI in addition to DI, including these categories likely overestimates rates of infertility.

The authors made the following disclosures: D.R.P. is a consultant for Biogen, Inc. and Pfizer, Inc., and a clinical trials investigator for Pfizer, Inc., EMD Serono, Priovant, Emerald Health, Kadmon, and Argenx. B.S. is a consultant for Argenx and has served as a clinical trials investigator for Argenx, AstraZeneca, and Elorac. The other authors have no conflicts of interest to disclose.