Jean Marie Antoine

Pregnancies after replacement of frozen-thawed embryos in a donation program

Eighteen patients with primary (n = 8) or secondary (n = 10) ovarian failure were enrolled in a donation program. In 15 cases, the oocytes were donated anonymously; in 3 cases, they were donated by the sister of the recipient. All the recipients had cyclic steroid replacement therapy that included estrogens and progesterone administered by the transdermal and tranvaginal routes, respectively. The embryos obtained were cryopreserved and replaced with no attempt at synchronization between donor and recipient. Steroid hormonal patterns were within the range for the normal menstrual cycle and endometrial biopsies taken on day 21 or 22 of the treatment cycles were independently assessed as being representative of day 21 +/- 2. Four of 12 transfers were successful (31%): 1 patient aborted at 6 weeks, and the three others were delivered, one normally and two by cesarian sections. The authors practice suggests the following: (1) steroid supplementation by transdermal and transvaginal routes is effective, (2) synchronization between donor and recipient is no longer required with the use of frozen-thawed embryos, and (3) the temporal window is large since all the replacements were done on day 14 of the cycle.

Comparison of growth hormone responses to growth hormone-releasing factor and clonidine* in women with normal or poor ovarian response to gonadotropin stimulation

OBJECTIVEnTo assess the reliability of growth hormone (GH) secretion tests using provocative agents in women of different ovarian status.nnnDESIGNnComparison of GH secretion in response to clonidine (Catapressan; Boehringer Ingelheim, Reims, France) and growth hormone-releasing factor (GH-RF).nnnSETTINGnUniversity Hospital, Hôpital Tenon, Paris, France.nnnPATIENTSnWomen categorized as normal (n = 6) or poor responder (n = 7) to ovarian stimulation with gonadotropins, depending on the follicular development attained at previous IVF attempts.nnnINTERVENTIONSnClonidine (0.300 mg administered orally) once and GH-RF (1 micrograms/kg IV) repeated twice. The tests were performed in random order in each individual on following cycles.nnnMAIN OUTCOME MEASURESnBasal and peak GH values, area under the curve (AUC).nnnRESULTSnPoor responder patients show significantly higher basal levels of FSH, GH, and insulin-like growth factor 1; FSH and basal GH levels are positively correlated. Peak GH levels and AUC are not significantly different in both categories of patients, whether GH-releasing factor or clonidine are used as provocative agents. True positive rate is 56.4% at the cutoff value of 7 micrograms/L, with no significant difference between the patients of the normally or poorly responding groups. At the 10-micrograms/L cutoff level, the true positive rate is almost half in the poor responder group (19.0% versus 38.9%), but the difference is not significant.nnnCONCLUSIONSnThese results raise concern about using the GH secretory response to a single clonidine administration as a predictive test of the therapeutic benefit that could be obtained by co-stimulating the somatotropic axis during a treatment with gonadotropins in poor responder patients, especially when their FSH basal levels are elevated.

Multiple pregnancies: the price to pay

Since 1980, the rate of multiple pregnancies due to assisted reproductive technology has been multiplied by 10, especially for twin pregnancies and for cases involving simple stimulation of ovulation. The prices paid are: an increase in prematurity (82% of deliveries); perinatal mortality (an increase of 74%); and transfer to intensive care units (95% of infants born of multiple pregnancies). This does not take into account the rise in cost per child, which increased by 1.9 for twins and 3.7 for triplets. The solution does not lie in selective embryo reduction but in the reduction of the number of embryos transferred.

Hormonal secretions in singleton pregnancies arising from the implantation of fresh or frozen embryos after oocyte donation in women with ovarian failure

Objective To determine whether levels of human chorionic gonadotropin (hCG), 17 β -estradiol (E 2 ), and progesterone (P) are different in the peri-implantation phase of fresh versus frozen embryos. Design Hormonal secretions were measured on days 9 and 11 after implantation and at 4, 5, and 6 weeks gestation. Patients Thirty-one pregnancies were achieved in 65 patients with ovarian failure. Seventeen singleton pregnancies developed after implantation of 4 frozen and 13 fresh embryos. Results Human chorionic gonadotropin and E 2 , contrary to P, were higher in cases of fresh embryos from the 9th day after transfer to the 5th week at which time they become statistically significant (respectively, for hCG and E 2 , 5,800.3 ± 332.3 versus 2,027.3 ± 916.3 [mean ± SD] mIU/mL for hCG and 562.3 ± 215 versus 291 ± 152 pg/mL for E 2 ). Conclusions This difference might be explained by either the higher number of fresh embryo replaced or by the fact that the number of blastomeres and also their metabolic activity could be reduced after freezing and thawing.

Ultrasonographic Prediction of Ovarian Hyperstimulatton (OHS) After IVF

The incidence of ovarian hyperstimulation syndrome (OHS) ranges from 3% to 6% for the moderate forms and from 0.3% to 4% the severe.1 If it is easy to predict this complication in cases of Polycystic Ovarian Disease (PCO);2 in all the other cases of stimulation, the reports concerning the correlations between the multiple variables (age, weight, type of stimulation, number of ampules of human Menopausal Gonadotropin (hMG) used) with OHS are conflicting. Daily monitoring of 17 B estradiol (E2) and sequential pelvic ultrasonography proved to be beneficial, but they may obviate OHS only after six to eight days of stimulation and a variable number of ampules used. As the pathophysiology of this syndrome is unknown, it is of interest to indicate some predictive factors to avoid cancelling cycles or being faced with severe complications. In 1987, Blankstein et al.,3 attempted to predict OHS by ultrasonographic determination of the number and the size of preovulatory ovarian follicles. Navot et al., in 1988,4 using a stepwise logistic regression performed on 22 variables, identified a “high-risk group” for this syndrome: “young and lean patients, who after relatively few ampules of hMG, develop high estradiol levels and multiple small follicles”.

Traitement des dystrophies ovariennes polykystiques au cours de fecondation in vitro. considerations physiopathogeniques

More than 60% of patients with polycystic ovary disease (PCO) cannot conceive after repeated ovulation inductions with Clomifene citrate although there is ovulation or more frequently follicle luteinization. Because of hyperstimulation, therapy with hMG has been superseded by low doses of purified FSH with variable results according to authors. It has been even claimed that there was no benefit to replace hMG with FSH. However, on the basis of the PCO physico-pathology, namely LH hypersecretion and androgen hyperproduction, it would be rational to associate the desensitization of the pituitary with LH-RH agonist and the ovary stimulation with variable doses of hMG or purified FSH. In the series where such therapy associating LH-RH agonists with purified FSH was applied, the results concerning suppression of LH and androgen secretion, and the occurrence of pregnancy were interesting. However, the risk of hyperstimulation still occurred. Thus, the first part concerns the critical review of these results while, in the second part, our experience in in vitro fecundation will be reported.