Premature Ovarian Failure

So, you and your partner have been trying to get pregnant for several months, and in keeping with the fertility guidelines for your age, you decide it’s time to seek out a fertility specialist. There are many different causes of infertility, but one the of more frustrating ones is called primary ovarian insufficiency (POI), which is also known as premature ovarian failure (POF). You are considered to have primary ovarian insufficiency (POI) if you are younger than 40 and your ovaries no longer normally ovulate (release eggs).

What Is Primary Ovarian Insufficiency (or Premature Ovarian Failure)?

At one time primary ovarian insufficiency (POI) was referred to as premature menopause.  This was inaccurate because women with POI can on occasion produce estrogen and ovulate, therefore having an infrequent period. However, there is a low probability of conceiving on their own, unlike women with a natural menopause who have no periods and therefore no chance of conceiving.

Technically speaking, primary ovarian insufficiency, commonly referred to as POI, is the development of hypergonadotropic (high FSH [follicle-stimulating hormone] level) hypogonadism (estrogen deficiency) with the cessation of normal function of ovaries in women before the age of 40. POI was previously referred to as premature ovarian failure (POF).

Even though the presenting symptoms are similar to menopause, POI is not a natural phenomenon. Natural menopause is defined by permanent cessation of menstrual periods for more than 12 months and occurs at an average age of 51. POI can be diagnosed at any age. In the U.S., POI affects 1 in every 1,000 women between the ages of 15-29 and 1 in every 100 women between the ages of 30-39. POI is associated with:

  • An absence of, or infrequent, irregular periods
  • Possible symptoms of estrogen deficiency, such as:
    • Vaginal dryness
    • Hot flashes
    • Mood swings
  • FSH levels in the menopausal range

What Causes POI?

In 75-90% of women who experience POI, the cause remains unexplained. Known causes of POI include:

  • Chromosomal defects, such as Turner syndrome and fragile X premutation carriers.
  • Certain genetic mutations and enzyme deficiencies.
  • A history of ovarian surgery.
  • Exposure to chemotherapy or pelvic radiation.
  • Autoimmune and metabolic disorders, such as galactosemia.

How is POI Diagnosed?

Most women with POI have a history of both normal puberty and regular periods prior to the development of POI, with the most common presenting symptom being a change in menstrual cycles.

The occurrence of hot flashes or vaginal dryness may be suggestive of POI when in combination with irregular periods or no period. However, the absence of these symptoms does not exclude POI.

If POI is suspected, evaluation may include:

  • Blood tests assessing a Day 2 or 3 FSH and estradiol level.
  • Blood test for AMH (anti-müllerian hormone) level.
  • A transvaginal sonogram, to assess the antral follicle count (AFC) in the ovaries.

The diagnosis of POI is made in women younger than 40 years old with irregular periods in association with an elevated FSH in the postmenopausal range. Estradiol levels will be low.

In situations when there is no period, a random FSH and estradiol level can be evaluated. In these situations, an elevated FSH in the postmenopausal range is once again consistent with POI. However, some may have occasional intermittent ovarian function, so a normal FSH and estradiol level may be seen in an ovulatory cycle.

Women with POI generally have an undetectable AMH level, and on transvaginal sonogram, ovaries will be small, with minimal to no follicles visualized.

In the setting of irregular periods or no period at all, it is important to exclude other endocrine causes of menstrual cycle dysfunction, such as thyroid disorder, which can be excluded by evaluation of a TSH level (thyroid stimulating hormone), as well hyperprolactinemia, which can be excluded by checking a prolactin level.

How is POI treated?

Unfortunately, there is no treatment for POI that will return natural ovarian function.

Important issues to consider in the management of POI include:

  • Estrogen-deficiency symptoms.
  • Emotional health.
  • Fertility.
  • Sexual function.
  • Bone health.
  • Cardiovascular health.
  • Risk for development of other endocrine disorders, such as:
      • Hypothyroidism.
      • Diabetes
  • Rarely, adrenal insufficiency.

The diagnosis of POI can be emotionally traumatic and increase the risk for depression and anxiety.  Part of this is due to the obvious interference with the desire to plan a family.

Treatment options related to POI are meant to stave off complications associated with reduced estrogen levels, such as hormone replacement therapy, as well as calcium and vitamin D supplementation, to decrease the risk of osteoporosis.

Unless there is an absolute contraindication, hormone replacement therapy can:

  • Reduce risk of osteoporosis.
  • Reduce risk of cardiovascular disease.
  • Maintain sexual health.
  • Improve quality of life.

How Does POI Affect Fertility?

Loss of ovarian function has obvious implications on fertility and the ability to conceive. Unfortunately, fertility treatments, such as IVF (in vitro fertilization) are often unsuccessful in women with POI, as the ovaries tend to be unresponsive to the stimulation medications.

Although POI affects ability to conceive, it does not preclude the ability to carry a pregnancy. As a result, women with POI are candidates for IVF with donor eggs.

Dr. Matthew Lederman is a board-certified Reproductive Endocrinologist and Infertility Specialist, and is often acknowledged for his compassionate care, devotion to patients and his clinical expertise. Prior to joining RMA of NY in 2014, Dr. Lederman treated patients at the Continuum Reproductive Center at St. Luke’s Roosevelt Hospital Center. After graduating from the University of Michigan, Dr. Lederman received his medical degree from the Chicago Medical School and completed his residency in Obstetrics and Gynecology as well as his fellowship in Reproductive Endocrinology and Infertility at the Albert Einstein College of Medicine/Montefiore Medical Center.