IVF endocrinology: the Edwards era

Abstract

Through pioneering human IVF as a global infertility treatment, Robert Edwards and his clinical partner Patrick Steptoe launched the field of IVF endocrinology. Following repeated failures with oocytes collected in human menopausal gonadotrophin (HMG) primed cycles timed to injection of human chorionic gonadotrophin (HCG), the first successful IVF pregnancy came from a spontaneous menstrual cycle. Intensive endocrine monitoring was used to track pre-ovulatory follicular development and collect a single ripe egg timed to the natural LH surge. Despite this groundbreaking achievement, ovulation induction was clearly required to make IVF treatment clinically robust and reliable. Ovarian stimulation with clomiphene citrate was used to achieve the first maternity from a superovulated human IVF cycle in 1980. HMG/HCG regimens were then successfully introduced-including substitution of 'pure' follicle-stimulating hormone as the principal ovarian stimulant. The application and success of IVF treatment were dramatically enhanced by the introduction of gonadotrophin-releasing hormone analogues that enabled elective control of endogenous gonadotrophin release during ovarian stimulation. Programmed gonadotrophin regimes yielding double-digit oocyte numbers became normal: 'more is better' was the ethos. Bob Edwards expressed increasing concern over the cost, complexity and potential long-term health risks of such high-order ovarian stimulation. In later life he repeatedly called for a return to minimalist approaches based on the natural menstrual cycle to improve oocyte quality over quantity. This article reviews the application of ovulation induction to human IVF and celebrates Edwards' abiding impact on the field, which firmly grounds him in the reproductive endocrinology pantheon.

Clinical Value of Basal Serum Progesterone Prior to Initiate Ovarian Hyper-Stimulation with GnRH Antagonists: A Retrospective Cohort Study

“…During the study period, women receiving this type of regimen systematically underwent a transvaginal sonography and a serum basal progesterone assessment on day 3 of the menstrual cycle (thus prior to initiation of hyper-stimulation). More specifically, inclusion criteria were as follows: (1) indication for IVF-ICSI, (2) regimen of COH with the use of gonadotropins and GnRH antagonists, (3) availability of serum progesterone assessment at day 3 of the menstrual cycle, (4) age 18-42 years, (5) normal uterine cavity (women with endometrial polyps, submucosal fibroids and uterine malformations were excluded) and (6) no hormonal treatment (estroprogestins, progestins or GnRH agonist) during the last 2 months prior to initiate the treatment cycle. Women could be enrolled for more than one cycle.…”

“…However, several essential issues of the procedure remains to be definitely clarified or improved, including the indications to treatment [1] and the clinical and embryological management [2] . A neglected but potentially relevant area of interest here is the monitoring of the controlled ovarian hyperstimulation (COH) [3,4] .…”

Low-cost in vitro fertilization: current insights

“…Although Edwards and Steptoe tried and then largely abandoned both this medication and tamoxifen,59,60 others have continued to demonstrate that clomiphene can be a cost-effective way to achieve full-term IVF pregnancies 60. The advantages of clomiphene include oral administration, low price, and widespread availability in many parts of the world 53.…”

“…At most, modest forms of ovarian stimulation aimed at stimulating the growth of a limited number of Graafian follicles should suffice 60,83,84…”

Redrawing the boundary of medical expertise: medically assisted reproduction and the debate on Italian bioconstitutionalism

“…Specifically, the Law obliged the treating practitioner to fertilize no more than three oocytes during one IVF cycle and to transfer all the embryos created into the patient's uterus simultaneously (Repubblica Italiana 2004). By setting this "three embryo" standard, the pro-life members of the Italian Parliament sought to prevent the creation of surplus embryos and their cryopreservation, the constitutive elements of IVF (Gianaroli et al 2000;Hillier 2013) and thereby to ensure the protection of a new technologically created entity -the embryo outside the women's body (Metzler 2011). Drawing on the concept of boundary-work (Gieryn 1983(Gieryn , 1995, I explore how the Italian Parliament justified the expansion of the jurisdictional powers of the State into a domain traditionally occupied by the medical profession, namely, the prescription of treatment methods, and how the Italian Constitutional Court justified the constitutional illegitimacy of the Parliament's actions.…”