For the majority of couples dealing with infertility, there is an identified cause for the problem. For about 15 percent of infertile couples, however, the cause of infertility has yet to be explained. These women are often thought of has having unexplained infertility. For these patients, endometrial receptivity for implantation is impaired.
Since the hormone progesterone is stimulated by luteinizing hormone and human chorionic gonadotropin during the luteal phase of the menstrual cycle, it is a key factor for the endometrium to undergo changes that allow implantation. Progesterone also sustains the survival of the embryo by shifting the immune system to produce non-inflammatory T-helper cytokines, which are extracellular signals that influence the immune cells to behave in a manner conducive to pregnancy.
When progesterone production is inadequate, luteal phase dysfunction also occurs, and implantation failure occurs as a consequence. Progesterone supplementation is the most commonly used therapy when luteal phase dysfunction is thought to occur. Luteal phase support is a common practice in IVF cycles, since luteal phase dysfunction may occur as a result of some assisted reproductive therapies, such as the use of gonadotropin-releasing hormone stimulating agents.
Controlled ovarian hyperstimulation is usually combined with intrauterine insemination (IUI) or in-vitro fertilization for couples with unexplained infertility. Some recent studies shown that luteal phase support with progesterone has dramatically positive effects on ovarian stimulation and IUI cycles for these patients. Other studies have shown no benefit of luteal phase support. With contradicting findings available, further studies are required to determine what exactly is the impact of luteal phase support on intrauterine insemination.
In a 2009 randomized control trial to determine the impact of luteal phase support to improve reproductive outcome, 200 women were randomized into two groups to undergo IUI with or without luteal phase support. The results of the study showed virtually no difference between treatment and control groups, since the pregnancy and live birth rates were not statistically different.
Supporting the luteal phase in IVF cycles may be a logical step to help improve pregnancy rates, however there is hardly consensus among practitioners regarding the use of progesterone supplements, especially in patients with unexplained infertility.
It is important as well to understand that luteal phase support is contraindicated for patients undergoing ovulation induction. If the goal of ovarian stimulation during IUI cycles is to stimulate multiple follicles to develop, then the treatment overrides the physiological feedback mechanisms that normally ensure that only one or two large follicles achieve ovulation. With multiple follicles and corpora lutea develop, large amounts of estrogen and progesterone are secreted, which suppress LH and FSH. Thus, it is important to ensure that the correct diagnosis of unexplained infertility has been made.