A woman's menstrual cycle consists of different phases. After ovulation the luteal phase starts and lasts until the next menstruation. It is named after the corpus luteum, the yellow body. This consists of the remnants of the ovulated egg in the ovary and produces different hormones, including progesterone. Progesterone stimulates proliferation of the lining of the uterus, preparing for implantation.
When in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), are used for subfertility treatment, fertilisation takes place outside the human body. It is standard protocol to obtain as many eggs as possible. The woman's pituitary gland is desensitised, making it possible to stimulate the ovaries. This process is called controlled ovarian hyperstimulation. In this way more mature eggs are produced, increasing the chance of successful fertilisation. This hyperstimulation causes a luteal phase defect, meaning that the multiple yellow bodies are unable to produce sufficient progesterone.
As a low progesterone level may lower the chance of implantation, the luteal phase needs to be supported. This may involve oral, vaginal or intramuscular progesterone, human chorionic gonadotropin (hCG) (which stimulates progesterone production) or gonadotropin-releasing hormone (GnRH) agonists. GnRH agonists stimulate the production of GnRH, a hormone responsible for follicle stimulating hormone (FSH) and luteinizing hormone (LH) which triggers ovulation and develops the yellow body. GnRH agonists are thought to restore LH levels and support the luteal phase naturally.
Many different interventions, dosages and administration routes of luteal phase support have been investigated. We made six different comparisons, with an average of six studies for each comparison. We found six statistically significant results. Progesterone was more effective than placebo for live birth and clinical pregnancy. There are two different forms of progesterone, micronized (natural) and synthetic. When we compared these the results favoured synthetic progesterone. When we compared progesterone with progesterone + a single dose of GnRH agonist, the results favoured GnRH agonist supplementation for live birth and clinical pregnancy. In the comparison of progesterone with progesterone + multiple-dose GnRH agonist the results again favoured GnRH agonist supplementation. We also found that the use of hCG was linked to a significantly higher risk of ovarian hyperstimulation syndrome (OHSS), a side effect.
Because the number of studies in each comparison was small, we cannot be too certain about the results. This uncertainty is enhanced by the unclear methodology and high risk of bias of most of the included studies.