NICHD Primary Ovarian Insufficiency Research Information

In its aim to understand, treat, and prevent infertility, NICHD conducts and supports laboratory research, clinical trials, and epidemiological studies that look at normal ovarian function and at how changes in that function impact overall health as well as fertility. Although much of this research is not specific to POI, our understanding of the condition benefits from these activities.

This research includes, but is not limited to:

• Investigations in genetics, genomics, and epigenetics and studies about how these factors and processes influence typical and atypical development and function, including ovarian development and function
• Basic biophysical mechanisms that underlie cell biology and tissue function and how these factors influence development that specifically targets the nervous, endocrine, and reproductive systems
• Improving existing diagnostics and creating new methods for detecting and diagnosing endocrine, metabolic, and reproductive diseases
• Integrated programs of basic, clinical, and translational research in developmental biology, endocrinology, neuroendocrinology, genetics, epigenetics, and other factors relevant to reproductive system disorders
• Research on the quality of gametes (precursors of sperm and eggs)
• Studies of the relationships among diet, reproduction, development, and infertility
• Research on fertility preservation and on how these types of assisted reproductive technologies may affect health and developmental outcomes

The causes of POI are still little understood. Although many of its symptoms can be treated successfully, infertility is unavoidable in most women with POI. Understanding more about the complex biology behind the condition will help scientists as they work to devise more effective ways to treat symptoms and, ultimately, to prevent the condition from developing. NICHD conducts and supports research on genes, hormones, and other contributory factors in its push to improve understanding and make further headway against POI.

• Institute Activities and Advances
• Other Activities and Advances

Institute Activities and Advances

Researchers in NICHD's Division of Intramural Research (DIR) are studying genetic factors that are known to cause or contribute to POI. NICHD researchers in the Program in Reproductive and Adult Endocrinology (PRAE) and those funded by the NICHD have identified several genes more common in women with POI than in women who do not have the disorder. One of these genes is FMR1, mutations in which are known to cause Fragile X syndrome; certain mutations in this gene have been linked to Fragile X-Associated POI (FXPOI). Other genes being investigated are BMP15, DAZL, and FOXO3.

Researchers are also investigating the causal role of autoimmunity in POI. Researchers in the NICHD's Section on Epigenetics and Development compared women with and without POI. They discovered that several autoimmune diseases were more common among women with POI, especially if they also had Turner syndrome. The findings suggest that factors contributing to the ovarian insufficiency seen in POI also might play a role in autoimmunity.

PRAE researchers also identified a potential target of the autoimmune response that causes some cases of POI and were able to slow the immune system attack on the ovaries in mice with POI. For details on this finding, visit NIH Researchers Slow Immune Attack on Ovaries in Mice.

Other research supported by the Fertility and Infertility Branch (FIB) has addressed issues related to eggs, their quality, and their quantity in POI, as well as ways to save the eggs as a way to preserve fertility. FI Branch research also examines various methods of assisted reproductive technology and their effectiveness.

In addition to the physical components of POI, the NICHD aims to reveal new evidence about the emotional aspects of the disorder so that healthcare providers can offer appropriate psychological support to women with POI. PRAE research has shown that women with POI are much more likely than other women to experience depression at some point during their lives.¹ Future studies will investigate whether hormonal changes, perhaps combined with a particular genetic makeup, might predispose some women to depression and anxiety.

PRAE research also showed that two-thirds of women were dissatisfied with the way they received their POI diagnosis from their healthcare provider. In addition, research has pointed to the positive role spirituality plays in patients' ability to cope with their diagnosis and suggest therapeutic avenues for reducing emotional suffering.²

Other Activities and Advances

• The National Centers for Translational Research in Reproduction and Infertility (NCTRI) (Formerly the Specialized Cooperative Centers Program in Reproduction and Infertility Research [SCCPIR]) is a national network of research-based centers, supported by the FI Branch, that aims to promote interactions between basic and clinical scientists with the goal of improving reproductive health.
• Researchers working for and with support from across the NIH have made significant advances in the understanding of the FMR1 gene and its relationship to Fragile X syndrome, Fragile X-Associated Tremor and Ataxia Syndrome and FXPOI. The NIH Research Plan on Fragile X Syndrome and Associated Disorders outlines research opportunities related to these three disorders and helps coordinate research and promote timely detection, diagnosis, treatment, and prevention of these disorders.
• In 2008, the NICHD co-sponsored a conference to devise a new approach to addressing ovarian insufficiency. The Institute joined other Institutes and organizations in the field to convene the conference, Orphan Mechanisms of Primary Ovarian Insufficiency: Passion for Participatory Research. The meeting recommended establishing an international research consortium and disease registry for POI, formed under the guidance of an umbrella organization, to provide a means of increasing basic and clinical knowledge about the disease.³