The birth control pill significantly affects ovarian reserve— or the number of immature eggs in a woman’s ovaries— which can be a predictor of future fertility.

This is according to a team in Denmark, who reported to the European Society of Human Reproduction and Embryology annual meeting last month that two markers for the ovarian reserve are markedly suppressed after prolonged birth control pill use: the levels of anti-Mullerian hormone (AMH) in the blood, and the number of early (antral) follicles (AFC) in the ovary.  Ovaries are also markedly shrunken after prolonged pill use.

“During the last three years we have counseled 900 women, and 300 men, about their ability to conceive naturally,” team leader Kathrine Birch Petersen told Bioscience Technology via email. “The proportion of oral contraceptive users was 28 percent. We were surprised to find several young women with apparent diminished ovarian reserve parameters (ovarian volume, AFC and AMH). We found out it was due to the pill.”

Masking naturally diminished ovarian reserve

Birch Peterson’s Fertility Assessment and Counseling Clinic at Copenhagen University Hospital is a public clinic in the Capital Region of Denmark. “The Clinic was initiated due to the increasing number of fertility treatments in Denmark,” says Birch Petersen. “Every tenth child is born after assisted reproduction.”

Her team decided to assess the reliability of preconception lifestyle and biological factors as predictors of fertility. Available evidence, which the new study does not challenge, has indicated that reproductive cycles return after a few months post-pill, with pregnancy likely among younger women within about six months

But one concern for women taking birth control pills long term has been whether reproductive status is masked by them.

The phrase “ovarian reserve” refers to the ability of ovaries to churn out oocytes (eggs) that are fertilization-competent.  The Danish group found that AMH and AFC levels were 19 percent and 16 percent lower, respectively, in pill users than in women not taking the pill. Furthermore, ovarian volume was significantly smaller by between 29 and 52 percent— with the greatest shrinkage occurring in women aged 19 to 29.9 years.

The study looked at 833 women (aged 19 to 46 years) attending the Fertility Assessment and Counseling Clinic from August 2011 to April 2012, both users and non-users of birth control pills. About 30 percent were former pill users.

Even after statistical adjustment for age, body-mass index, smoking, maternal age at menopause, maternal smoking during pregnancy and prematurity, AMH levels were still up to 30 percent lower, and AFC levels were up to 20 percent lower, in pill users than non-pill users.

Not permanent

Birch Petersen’s team does not believe these changes are permanent. But as a result of the study, she said, women in the Pre-conceptional Care Program who have been on the contraceptive pill are now advised that their ovaries may look older and smaller, and may possess only a few small antral follicles, with low levels of AMH for a period of time after stopping. They are told this likely does not reflect future fertility for most women.

But it could matter to women undergoing premature menopause. Naturally diminished ovarian reserves could be masked by the above. It is therefore possible ovarian reserve assessment should be repeated after stopping birth control pills.

“Worldwide, 160 million women are on the pill,” Birch Petersen told Bioscience. “One percent will go into early menopause before the age of 40. The pill can mask the symptoms of early menopause, and this is why women could consider repeating the tests after six months [off the pill], if they have a low ovarian reserve.”

Next up, says Birch Petersen: “To examine what happens with the ovarian reserve parameters after one, three and six months.” The team will be writing a paper on the conference data and sending it out for publication this fall.

Note: This story has been updated to correct a typo. 160 million women are on the pill, not 16 million.