Fertility Drugs

Progesterone a Fertility Drug for Endometrial Support

Progesterone is necessary for the proper development of the endometrium, which is the lining of the uterus.  During the first half of the cycle (from the beginning of menses to ovulation), estrogen stimulates the endometrium to thicken and become more vascular. After ovulation, progesterone is produced (in addition to estrogen) and progesterone causes the endometrium to undergo the final changes (luteinization) necessary to prepare for implantation of an embryo.

Once the ovarian follicles rupture and release the eggs, the remaining structure on the ovary is termed the corpus luteum. The corpus luteum begins to produce progesterone for endometrial support. Elevated progesterone levels are one indication that successful ovulation has occurred. Progesterone levels are usually less than 2 ng/ml during the early part of the cycle and can rise to above 12 ng/ml within 5-6 days after ovulation. Once the embryos embed in the endometrium, and the placenta forms, the placenta produces progesterone.

Inadequate progesterone in the luteal phase of the cycle can lead to a “luteal phase defect”.  This condition occurs when there is insufficient progesterone to properly support endometrial development. Poor ovulatory function is usually the underlying problem and optimizing the ovulation induction treatment protocol will usually improve the progesterone production during the luteal phase and correct the “luteal deficiency”. Treatment is complex and sometimes the wrong doses of Clomid® can actually cause a “luteal phase defect”. Exogenous treatment using progesterone injections, vaginal micronized capsules (Prometrium®), vaginal progesterone gels (Prochieve® or Crinone®), or a vaginal insert (Endometrin®) can also be effective.

Progesterone injections (50 mg or 1 ml of progesterone in oil) are commonly given after egg retrieval during an IVF cycle. This is a very effective treatment but can be painful with time as the “oil” tends to accumulate, it is thick and difficult to inject intramuscularly (usually requires a 1.5-inch needle). A new progesterone formulation that is less viscous and easier to inject is now available in the US (requires compounding) which uses Ethyl Oleate as the base rather than peanut, cottonseed or sesame oil. This has been available in Europe for several years.

During frozen embryo transfer (when Lupron® and exogenous estrogen such as oral Estrace® is used) cycles both intramuscular and transvaginally progesterone is often used to optimize the endometrial development since the ovaries are not making any progesterone on their own.

Treatment cycles using oral ovulation enhancing agents such as Clomid® or Femara® prior to intrauterine insemination (IUI) may be supplemented after the IUI with vaginal progesterone preparations.

Progesterone is virtually always administered to patients undergoing ovulation induction cycles in conjunction with GnRH agonists (Lupron®) or GnRH antagonists (Ganirelix®, or Cetrotide®) for IVF. This is because Lupron®, Ganirelix®, and Cetrotide® interfere with the body’s normal cascade of hormonal events leading to progesterone production by “inhibiting or blocking” GnRH production.