Several medications have been found to increase implantation rates with in vitro fertilization (IVF) when given as adjuncts to follicle stimulating hormone (FSH) stimulation of the ovaries in preparation for oocyte retrieval. Gonadotropin-releasing hormone (GnRH) agonists, oral contraceptives (OCs), and estrogen pretreatment help to synchronize the follicular cohort resulting in an improved ovarian response. Metformin (MET) increases implantation in PCOS women having IVF and dramatically reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in these women. Growth hormone (GH) markedly increases implantation in poor-responding women having IVF. Small doses of human chorionic gonadotropin (hCG) are used to provide LH activity allowing use of pure FSH products and the pen devices that deliver graduated FSH doses. Low-dose aspirin (ASA) increases ovarian response and implantation, and reduces the incidence of severe OHSS. Drugs such as letrozole that increase androgens may prove to be useful agents to increase ovarian response in poor responders.

The use of gonadotropin-releasing hormone agonists (GnRHa) for prevention of chemotherapy-induced gonadotoxicity remains controversial. With the initial dose of GnRHa, the pituitary gland releases endogenous gonadotropins. This initial follicle stimulating hormone (FSH) release stimulates the ovary. After continued GnRHa exposure, further FSH release is prevented. Gonadotropin-releasing hormone analogues can be administered in many formulations with different durations of action. The most common side effects of GnRH analogues are related to the subsequent estrogen deprivation. Vasomotor symptoms, hot flushes, night sweats, vaginal dryness and headaches can occur. Cotherapy of a GnRHa during chemotherapy has been under investigation since the mid 1990s. If prolonged GnRHa administration decreases ovarian blood flow, then less chemotherapy may reach the ovary. Direct effects of GnRHa or FSH on ovarian tissue may influence ovarian response to chemotherapy. For GnRHa to be of benefit to fertility preservation, they would likely need to spare both oocyte quantity and quality.

This chapter presents a study which recognized that the resistance index (RI) of the uterine arteries was around 0.88 until day 13 of a 28-day cycle. The researchers measured the pulsatility index (PI) in 8 women with spontaneous cycles, 20 women undergoing induction of ovulation with clomiphene citrate, and 11 women undergoing controlled ovarian stimulation for in-vitro fertilization with gonadotropin-releasing hormone agonists (GnRH-a), human menopausal gonadotropin (hMG), and human chorionic gonadotropin (hCG). The intraovarian PI showed a gradual decrease from the early follicular (1.05) through the periovulatory (0.99) to the mid-luteal phase (0.85). The detection and quantification of follicular vascularity with pulsed color Doppler is used to predict oocyte recovery rate and hence may be useful in determining the most appropriate time to administer hCG. Oocyte/embryo selection for transfer may benefit from a brief color Doppler examination of each follicle at aspiration and pooling of oocytes with respect to follicles.

NSAIDs are widely considered as the first-line therapy for the pain associated with endometriosis. Combined oral contraceptive pills (COCPs) are generally recommended as the second-line therapy for endometriosis pain. A 2007 Cochrane review concluded that COCPs are at least as effective as gonadotropin-releasing hormone (GnRH) agonists. Medroxyprogesterone acetate is comparable to the androgen danazol, with both agents reducing pain scores by 50-74% compared with placebo. An SC form of depot medroxyprogesterone appears to relieve endometriosis as effectively as the proven approach of the GnRH agonist leuprolide acetate. Cochrane review has shown that there is generally equivalent pain relief achieved with multiple endocrine therapies for endometriosis. The myriad menopausal, androgenic, and hepatic side effects from some of the endocrine agents (e.g. danazol) used to treat endometriosis should serve to underline the importance of ED physician communication and follow-up arrangements with longitudinal care providers.

The future of assisted reproduction lies in optimization of each treatment phase starting with ovarian stimulation through laboratory procedures, selecting the best embryo for transfer, embryo transfer, luteal phase support leading to pregnancy, and the birth of a healthy single ton baby. Gonadotropin-releasing hormone (GnRH) agonists have changed the course of ovarian stimulation for in vitro fertilization (IVF). GnRH antagonists have been introduced recently in ovarian stimulation for pituitary suppression. High implantation and pregnancy rates in oocyte donation cycles irrespective of acceptors' age imply that ovarian stimulation impairs endometrial receptivity in stimulated cycles. Embryo transfer procedure plays a pivotal role in the success of assisted reproduction. Improving embryo implantation continues to pose a major challenge to clinicians. The future developments in assisted reproduction should encompass individualized approach to ovarian stimulation, vitrification, single blastocyst transfer, and development of new tools for genetic testing.

This chapter discusses the physiology of the luteal phase both in natural and stimulated cycles, with emphasis on the current evidence-based approaches for luteal phase support in assisted reproduction. Progesterone (P) and estrogen (E) are required to prepare the uterus for embryo implantation and to modulate the endometrium during the early stages of pregnancy. A meta-analysis of all available quasi randomized trials showed that the use of gonadotropin-releasing hormone (GnRH) agonists increased in vitro fertilization (IVF) pregnancy rates by 80-127 percent in women who responded normally to exogenous gonadotrophins. It was shown that the addition of a high dose of E2 to daily P supplementation significantly improved the probability of pregnancy in women treated with a long GnRH agonist protocol for controlled ovarian stimulation. Vaginal P supplementation before embryo transfer may be useful in quieting uterine contractions and thereby reducing embryo displacement.