Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment

Replacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because of the known rapid recovery of pituitary function after antagonist cessation. This randomized two-center study was performed to compare nonsupplemented luteal phase characteristics after three different strategies for inducing final oocyte maturation. Forty patients underwent ovarian stimulation using recombinant (r-)FSH (150 IU/d, fixed) combined with a GnRH antagonist (antide; 1 mg/d) during the late follicular phase. When at least one follicle above 18 mm was observed, patients were randomized to induce oocyte maturation by a single injection of either r-human (h)CG (250 microg) (n = 11), r-LH (1 mg) (n = 13), or GnRH agonist (triptorelin; 0.2 mg) (n = 15). Retrieved oocytes were fertilized by either IVF or intracytoplasmatic sperm injection, depending on sperm quality. Embryo transfer was performed 3-4 d after oocyte retrieval. No luteal support was provided. Serum concentrations of FSH, LH, estradiol (E(2)), progesterone (P), and hCG were assessed at fixed intervals during the follicular and luteal phase. The median duration of the luteal phase was 13, 10, and 9 d for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.005). The median area under the curve per day (from 4 d post randomization until the onset of menses) for LH was 0.50, 2.34, and 1.07 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.001). The median area under the curve per day for P was 269 vs. 41 and 16 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P < 0.001). Low pregnancy rates (overall, 7.5%; range, 0-18% per started cycle) were observed in all groups. In conclusion, the nonsupplemented luteal phase was insufficient in all three groups. In the patients receiving r-hCG, the luteal phase was less disturbed, compared with both other groups, presumably because of prolonged clearance of hCG from the circulation and the resulting extended support of the corpus luteum. Despite high P and E(2) concentrations during the early luteal phase in all three groups, luteolysis started prematurely, presumably because of excessive negative steroid feedback resulting in suppressed pituitary LH release. Hence, support of corpus luteum function remains mandatory after ovarian stimulation for IVF with GnRH antagonist cotreatment

Preconception care and fertility

Preconceptional health has been shown to be an important determinant of fertility, fecundity and perinatal outcomes. In recent years the impact of periconceptional factors on developmental programming, and the health of the resultant child have become increasingly clear. Since fertility specialists care for couples during this critical phase, they have a unique opportunity to collaborate with the couple to optimise preconceptional health and thus fertility and pregnancy outcomes. In this review article, the current evidence available for the importance of preconceptional health care is considered, specific lifestyle and dietary interventions are described and the care of the medically complicated patient prior to fertility treatment is discussed. Finally strategies for overcoming challenges in implementing preconceptional care into the fertility clinic are addressed

Follicle development during the normal menstrual cycle

An understanding of the factors which determine initiation of follicle growth, recruitment and dominant follicle selection may increase our understanding of the underlying process of ovarian aging. In this article, these aspects of the normal menstrual cycle are reviewed. The morphological and endocrinological development in the early follicle is described from the primordial follicle stage. The degree of follicle-stimulating hormone (FSH) dependency is discussed, as is the relationship of estradiol (E2) production to follicle diameter. The principles governing mono-follicular selection are outlined, and the FSH 'threshold' and 'window' concepts are highlighted. Maximum FSH levels in the early follicular phase are shown to be variable between individuals. The relevance of this and the means by which individual sensitivity to FSH may be altered at the ovary in the context of ovarian aging are discussed

Impact of ovarian hyperstimulation on the luteal phase

The contemporary approach to ovarian stimulation in IVF treatment results in supraphysiological concentrations of progesterone and oestrogen in the luteal phase. These sex steroids act directly and indirectly to mature the endometrium, thus influencing its receptivity to implantation. The development of endometrial receptivity is a complex process that may be altered by inappropriate exposure to sex steroids. Alterations in the oestrogen to progesterone ratio, growth factor concentrations and cell adhesion molecule profiles may occur after ovarian stimulation, potentially affecting the receptivity of the endometrium. Recent clinical IVF studies have shown that implantation rates and corpus luteum function are influenced by oestrogen concentrations during the early luteal phase. Few comparative studies have been performed, but after ovarian stimulation there is a reduced implantation rate and a higher pregnancy loss rate before pregnancies can be detected clinically compared with natural cycle conceptions. Novel approaches to ovarian stimulation aimed at achieving a more physiological luteal phase endocrinology are now being developed. Data from a recent pilot study by our laboratory, involving minimal ovarian hyperstimulation and no luteal phase support, are discussed

Embryo implantation: biology, evaluation, and enhancement

Purpose of review: implantation is an essential step in the development of a pregnancy, but often fails in humans. In assisted reproductive technologies, implantation failure continues to impair treatment outcomes, with distressing results for patients and physicians.Recent findings: morphokinetics, comprehensive chromosome screening, and the analysis of embryo-derived products detectable in spent culture media offer new means of assessing embryo viability. However, all await validation in randomized controlled trials. Genomic, transcriptomic, and secretomic technologies are similarly being exploited to define specific biomarkers of endometrial receptivity with the aim of identifying novel therapeutic interventions. However, to date no single, clinically relevant molecular marker capable of indicating endometrial receptivity has been reported. Recent work continues to describe the key signalling pathways which result in acceptance or rejection of the implanting embryo. In-vitro studies have revealed that the decidualized endometrium plays an important role in natural embryo selection, which could change our understanding of the aetiology and treatment of reproductive failure.Summary: recent developments in analytical techniques have initiated a search for biomarkers of embryo quality and endometrial receptivity, and in-vitro studies have revealed novel roles for the decidualized endometrium as a biosensor of embryo qualit