Didier Chardonnens

Possible interactions between leptin, gonadotrophin-releasing hormone (GnRH-I and II) and human chorionic gonadotrophin (hCG)

Leptin is a metabolic signal to the reproductive axis, where it increases the plasma levels of luteinising hormone (LH) and follicle stimulating hormone (FSH). Since the placental regulation of human chorionic gonadotrophin (hCG) mimics that of the pituitary LH, we undertook this study to see if leptin could be involved in the secretion and synthesis of hCG in first-trimester trophoblast. We incubated cytotrophoblastic cells (CTB) with GnRH-I or GnRH-II, for 4 or 48 h and collected the media at different times thereafter. GnRH-II was more potent than GnRH-I when incubated for 4 h with CTB. Leptin secretion, as measured at 4 h, was significantly stimulated by GnRH-II. When measured at 24 h leptin values were also increased as compared to controls. Neither GnRH-I, nor GnRH-II had any effect on leptin secretion when incubated for 48 h with CTB. Leptin was also added to perifused placental explants, and samples (in which hCG was measured) were collected every 3 min. Leptin significantly stimulated hCG secretion by explants and induced a pulse of hCG immediately (within 6 min) after its injection, increasing significantly the area under the curve (P=0.04) and the amplitude (P=0.02) of hCG pulses. We conclude that GnRH-II is more effective than GnRH-I in stimulating leptin secretion. This difference could be explained by the existence of two different types of placental GnRH receptors or two different pathways of GnRH degradation. Furthermore, we observe that leptin has a significant stimulatory effect on hCG pulsatility.

Triptorelin acetate administration in early pregnancy : case reports and review of the literature

When using a long protocol with cycle day 23 gonadotrophin-releasing hormone agonists (GnRH-a) administration, an elevated estradiol level or a missed period 10-14 days after initiating pituitary downregulation should alert the physician to the possibility of a pregnancy. We report 4 pregnancies occurring during pituitary downregulation with Triptorelin acetate in 366 in-vitro fertilization (IVF) cycles resulting in 3 deliveries of 4 normal neonates at term and 1 first trimester abortion. This supports published data reporting a 1% spontaneous pregnancy incidence in women undergoing pituitary desensitization GnRH-a during the luteal phase prior to planned IVF treatment, a 15.9% abortion rate and a 1.7% malformation rate. Our cases together with other published data suggest that pregnancy outcome is not adversely affected by GnRH-a administration during the luteal phase of the conception cycle. However, long term follow-up of these babies is still lacking and the number of reported cases is too small adequately to rule out the possibility of any detrimental effect related GnRH-a administration in pregnancy.

The apparent late half-life of human chorionic gonadotropin (hCG) after surgical treatment for ectopic pregnancy A new approach to diagnose persistent trophoblastic activity

OBJECTIVE The disappearance kinetic of human chorionic gonadotropin (hCG) follows a biexponential decay with a rapid initial fall followed later by a slow disappearance. This kinetic is characterised by two half-lives: an early and a late. The objective of this study was to determine if and which half-life could be used clinically to detect persistent trophoblast after conservative surgery in patients with ectopic pregnancy. DESIGN Retrospective analysis of patients having undergone salpingostomy by laparoscopy for an ectopic tubal pregnancy between January 1990 and October 1993. SETTING Gynaecology Department of an University Hospital. PATIENTS 104 women with diagnosed tubal ectopic pregnancy were treated by salpingostomy performed under laparoscopy. In seven cases, persistent trophoblast was diagnosed on the basis of plateauing or increasing peripheral hCG values. MAIN RESULTS From the individual disappearance curves of hCG we calculated the early half-life (early T0.5, from samples obtained between 0 and 48 h postsurgery) and the late half-life (late T0.5, from samples obtained between 2 and 7 days postsurgery). Late T0.5 but not early T0.5 were significantly (P<0.0001 and P=0.416 respectively) longer in women (n =7) in whom a persistent trophoblast was diagnosed. Early T0.5 was dependant on the preoperative value of hCG, whereas late T0.5 was independent. We propose to use late T0.5 as a parameter to follow ectopic pregnancies after treatment.