New POI Guideline Streamlines Diagnosis

An updated guideline for the management of premature/primary ovarian insufficiency (POI) simplifies criteria for an early diagnosis to better inform treatment.

The guideline, published in the journal Climacteric, includes 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI based on the latest evidence.

New data suggest a global POI rate of approximately 3.5%, higher than previously thought, the authors noted. The guideline was a joint effort by the European Society of Human Reproduction and Embryology (ESHRE), American Society for Reproductive Medicine (ASRM), Centre for Research Excellence in Women’s Health in Reproductive Life (CRE WHiRL), and the International Menopause Society (IMS).

“This update is vital to increase education to healthcare providers regarding the importance of pursuing a prompt diagnosis,” said Mark Trolice, MD, professor at the University of Central Florida, Orlando, and director of The IVF Center in Winter Park, Florida, in an interview.

“In addition to infertility, POI has significant negative health consequences. By establishing an early diagnosis, healthcare providers can implement effective preventive strategies,” said Trolice, who was involved in reviewing the guideline.

“The classic symptoms of ovarian insufficiency are menopausal symptoms due to the hypoestrogenic ovaries, such as vasomotor symptoms of hot flashes and vaginal dryness,” he noted.

The incidence of POI has remained steady at approximately 1% in the United States, Trolice told Medscape Medical News. Among ethnic groups, POI occurs at similar frequencies in White, Hispanic, and Black women but at lower frequencies in women of Asian descent, he said.

Key Changes

Several significant changes from the previous guideline issued in 2015 include new diagnostic criteria. The guideline prompts the diagnosis of POI if the patient experiences, before the age of 40 years, amenorrhea or irregular menstrual cycles for at least 4 months and her follicle-stimulating hormone (FSH) level > 25 IU/L.

“Other criteria have used 3 months of amenorrhea and FSH > 30 IU/L that is repeated 1 month apart without intervening menses,” Trolice told Medscape Medical News.

How It Plays Out in Practice

After meeting the initial new diagnostic criteria, patients with a history of previous chemotherapy, radiotherapy, pelvic or ovarian surgery, or bilateral salpingo-oophorectomy should be diagnosed with iatrogenic POI, according to the updated algorithm.

Patients not in those categories should be counseled and educated about genetic testing options that are now available, according to the guideline. Although access to next-generation sequencing is not universally available, it is important to use, when possible, to determine the etiology of POI to inform risk assessment at the individual and family level, the authors wrote.

Those who opt for genetic tests and have normal results should be screened for autoimmune conditions, according to the algorithm.

Other notable updates include a recommendation to use anti-Müllerian hormone for confirmation, but not as the primary diagnostic test for POI. The guideline also includes information about changes in muscle parameters associated with POI (an emerging area of interest in need of more research) and a recommendation for bone mineral density testing using dual-energy x-ray absorptiometry every 1-3 years in women with POI who have osteoporosis or low bone density, based on individual risk factors.

In addition, the guideline recognizes, with a strong recommendation, that healthcare providers should be aware of the potentially significant impact on psychological health and quality of life and offer psychological health and quality-of-life assessments to all women with POI.

Limitations and Research Gaps

The authors acknowledged that supporting evidence for most POI management options is limited, but the guidelines address an expanded list of 40 clinical questions that reflect emerging knowledge about the condition, such as the reduced role of anti-Müllerian hormone in diagnosis, and including preservation of fertility, use of hormone therapy, and use of complementary nonhormonal management strategies, they wrote.

Clinical Considerations for Fertility and Beyond

The cause of POI is unknown in 75%-90% of cases; however, with the advances in analysis of genetic mutations, approximately one third of women with POI can be diagnosed with a genetic cause, Trolice told Medscape Medical News.

“The evaluation consists of a karyotype, serum prolactin and thyroid-stimulating hormone (TSH) testing, along with adrenal antibody and fragile X messenger ribonucleoprotein 1 (FMRP) testing,” said Trolice. “Women diagnosed with POI can experience intermittent ovulation function resulting in pregnancies in 5%-10% of cases. Nevertheless, the standard approach to having a child is oocyte donation, embryo donation, and adoption,” he said.

A woman with POI who has no desire for children and no contraindications can be treated with hormone replacement therapy until the natural age of menopause for symptomatic relief of hypoestrogenism and to maintain bone mineral density, said Trolice. Weight-bearing exercises, along with daily elemental calcium and vitamin D3, can benefit women with low bone mineral density, he noted.

“Future research should address improved genetic analysis for the cause of POI as well as options for fertility that may involve the use of stem cells and/or activation of primordial ovarian follicles,” Trolice added.

The guideline wasdeveloped and funded by the ESHRE, ASRM, CRE WHiRL, and IMS. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of ObGyn News.

Heidi Splete is a medical journalist based in the Washington, DC, area, with more than 25 years of experience covering a range of medical specialties. She began her career as a full-time medical journalist for the International Medical News Group, now part of Medscape, and she served as managing editor of Dermatology News for 2 years before becoming a freelance writer. Her work includes reporting the latest medical news and covering medical meetings remotely and in person. She has a master’s degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University.