Assisted fertilization

Testosterone to improve women’s fertility in assisted reproduction treatments

In the United States several fertility clinics are starting to administer testosterone, mainly transdermally, to increase the number of follicles produced by women undergoing in vitro fertilization treatments.

In some cases, women are asked to take a supplement based on DHEA  ( dehydroepiandrosterone ) which is a steroid hormone, one of the precursors of testosterone.

DHEA is typically administered to slow aging and improve muscle mass.

Now supplementing this precursor would serve to increase pregnancy and birth rates in women who are not responding well to IVF therapy. There is still not enough data to draw any conclusions on the subject even though a new study, published in PNAS ( Proceedings of the National Academy of Sciences)   suggests that male hormones, also called androgens, help guide the development of follicles (structures that contain and finally, they release the oocytes which can be fertilized by the sperms).

Research describes how male hormones increase follicle production in tested mice. The authors believe the study provides potential biological targets to improve fertility in women with reduced ovarian reserve and/or who produce few or no follicles in response to drugs used in IVF treatments .

A great debate has arisen among endocrinologists on the effectiveness of this  male hormone  in the treatment of MAP. This study does not resolve the controversy, but it does suggest that we cannot dismiss male hormones a priori. They might actually do something useful.

As Dr. Vidali states : “ DHEA is not for everyone. First, it increases the number of follicles, but it is not clear that it increases the number of pregnancies. So with #fivet you have more eggs but the chance of pregnancy ends up being the same. Secondly, DHEA activates the immune system and therefore can cause miscarriages. So I certainly would not recommend it in patients who have already had miscarriages. For the moment, therefore, use DHEa only in special cases “

In the study, male hormones were found to promote follicle development in two ways. Firstly by preventing the follicles from dying at an early stage. The authors hypothesize that if a woman does not have enough androgens (male hormones), more follicles than necessary die in the follicular phase, thus preventing them from maturing and reaching the release of the egg cell. Second, androgens make ovarian cells more sensitive to follicle stimulating hormone (FSH) which promotes follicle growth. Androgens allow for the creation of more FSH molecule receptors on the surface of ovarian cells which initiates the process of selecting the dominant follicle in response to the hormone.

It was seen that administering small doses of androgens to mice concurrently with the equivalent of drugs administered to women on ART therapy, developed more mature follicles, compared to mice that did not receive androgens. The androgen-treated female mice also released large numbers of egg cells with ovulation.

The drugs used in IVF treatments are designed to do just that: improve ovulation (production and release of the egg cell from the ovaries. Unfortunately, these drugs are not always effective in women with decreased ovarian reserve.

 If the study data is confirmed in clinical trials, androgens could be used in women with reduced ovarian reserve to increase their ability to produce oocytes (but within the limits previously expressed by Dr. Vidali).

Bibliography:

Aritro Sen, Hen Prizant, Allison Light, Anindita Biswas, Emily Hayes, Ho-Joon Lee, David Barad, Norbert Gleicher, and Stephen R. Hammes; Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and  microRNA-125b  expression Proceedings of PNAS 2014 111 (8) 3008-3013;published ahead of print February 10, 2014,

Kathryn Barlow is an OB/GYN doctor, which is the medical specialty that deals with the care of women's reproductive health, including pregnancy and childbirth.

Obstetricians provide care to women during pregnancy, labor, and delivery, while gynecologists focus on the health of the female reproductive system, including the ovaries, uterus, vagina, and breasts. OB/GYN doctors are trained to provide medical and surgical care for a wide range of conditions related to women's reproductive health.

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