Female Infertility and NIH Women's Health Research

Signs, Symptoms, and Risk Factors

Infertility is typically defined as not being able to conceive after 12 months of regular, unprotected sex. It can affect both men and women; male factors contribute significantly to infertility in about half of cases.¹ Infertility also includes cases where women can achieve pregnancy but are not able to carry the pregnancy to term due to miscarriages, stillbirths, or other complications.² The term "subfertility" is sometimes used interchangeably with infertility, but it can also describe any form of reduced fertility in which conception takes a prolonged period of time. In the United States, around 13% of women aged 15 to 49 years have impaired fecundity.³

A variety of factors can contribute to female infertility, including:^{4 , 5}

• Ovulatory dysfunction, which can be caused by conditions such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI), and certain endocrine disorders
• Conditions that obstruct the fallopian tubes, such as pelvic inflammatory disease (PID)
• Age
• Endometriosis
• Uterine fibroids
• Previous pelvic surgery

Other factors, such as body weight (e.g., being underweight, having obesity), smoking, and environmental exposures, can increase the risk of female infertility as well. Despite the variety of known causes for infertility in women, around 15% to 30% of female infertility cases are considered idiopathic.⁵

Diagnosis and Treatment

A comprehensive medical history that includes reproductive history, menstrual history, and surgical history can help determine if ovulatory dysfunction, uterine or tubal pathologies, or prior pelvic surgery are potential factors in female infertility. Diagnosis also typically involves a physical exam to assess patients for signs and symptoms of PCOS, uterine fibroids, endometriosis, and other conditions that can compromise fertility. Certain laboratory tests can evaluate ovulatory function or ovarian reserve. Hysterosalpingography can be used to detect obstructions in the fallopian tubes, and transvaginal ultrasound, sonohysterography, and hysteroscopy can be used to identify structural abnormalities in the uterus.^{5 , 6}

Treatment strategies for female infertility vary depending on the underlying causes. Women with ovulatory dysfunction may respond well to pharmacological interventions. For example, letrozole and clomiphene citrate have been used to induce ovulation in women with PCOS.⁷ In vitro fertilization (IVF) can increase the chances of pregnancy when tubal dysfunction is a contributing factor to female infertility (e.g., in women with PID or endometriosis), and both IVF and intrauterine insemination may be beneficial for women with idiopathic infertility.⁵ Hysteroscopic surgery can remove intrauterine lesions that prevent implantation, such as uterine fibroids, lesions from endometriosis, and cervical polyps.^{8 , 9}

In addition to the physical effects of infertility, there is a significant psychological impact. Infertility has been shown to affect self-esteem and increase rates of anxiety and depression.^{10 , 11} Some of the medications used to treat female infertility, including letrozole and clomiphene citrate, have potential side effects that can contribute to poor mental health, fatigue, headache, and interrupted sleep.¹¹ Miscarriage (especially recurrent miscarriage) and stillbirth are also associated with a high risk of depression.¹²

Ongoing Research

Current research in female infertility encompasses a wide array of topics. Studies are investigating novel methods for diagnosing, managing, and preventing the conditions that can compromise female fertility. These include gynecologic comorbidities such as PCOS, endometriosis, and uterine fibroids. There is also interest in improving fertility in women who are over the age of 35. Other research focuses on developing fertility-sparing treatments for other conditions; the emerging field of oncofertility is concerned with finding strategies for preserving fertility in people who require chemotherapy, radiotherapy, and other treatments for cancer.^{13 , 14}

The Fertility and Infertility Branchat the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is dedicated to supporting research that can help people who are experiencing infertility. This branch funds basic, clinical, and translational research on a wide variety of topics related to reproductive health, including ovarian and uterine function, preimplantation genetics and development, reproductive neuroendocrinology, and fertility preservation. The Fertility and Infertility Branch also supports a national network of centers that promote the establishment of translational research programs in the reproductive sciences. This network, the National Centers for Translational Research in Reproduction and Infertility (NCTRI), also provides resources for researchers who are pursuing careers in the field of reproduction and infertility research.