Maud Pasquier

FOXO3a variants in patients with premature ovarian failure

© 2007 The Authors Journal compilation

L'insuffisance ovarienne prématurée

Premature ovarian failure (POF) is defined by at least four months of amenorrhea with elevated gonadotropins (usually above 40 UI/L) detected on two occasions a few weeks apart, in a woman before the age of 40. It occurs in 1 out of 10,000 in women below the age of 20, 1/1,000 below 30 and 1% in women before the age of 40. In 80% of POF cases, the etiology is unknown, except for Turner syndrome. The different etiologies identified are 1) iatrogenic following chemotherapy and/or radiotherapy, 2) autoimmune, 3) viral, 4) genetic (RFSH, FOXL2, FRAXA, BMP15, GDF9, GALT, 17 hydroxylase...). Management of these patients includes hormone replacement therapy in order to avoid an increase in cardiovascular risk and osteoporosis related to hypoestrogenism. Infertility is common, as only 3 to 10% of the patients will have natural conception. When fertility is desired, women with POF should be oriented towards oocyte donation centers. Research is currently performed in order to identify new genes involved in POF.

Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels

BACKGROUND Serum androgen levels correlate with ovarian sensitivity to follicle-stimulating hormone (FSH) but in practice, standard baseline serum testosterone (T) levels prior to in-vitro fertilization (IVF) may not be the most appropriate marker for determination. METHODS Infertile women enrolled in an IVF programme were included in this study. Serum T and Delta4-androstenedione (A), and the androgen precursor 17-hydroxyprogesterone (17-OHP) were measured before and 24 h after a gonadotrophin-releasing hormone agonist stimulation test (GAST). An early follicular phase antral follicle count (AFC) was also performed. Patients were subsequently enrolled in a long gonadotrophin-releasing hormone agonist protocol with a standard FSH dose (150 IU) for 7 days to assess the association between androgen levels and ovarian responsiveness to FSH. RESULTS The GAST elicited a significant increase in serum androgen levels that was well correlated with AFC. 17-OHP showed the greatest response to GAST and strongest correlation with AFC. The 17-OHP response to GAST differentiated patients with high ovarian reserve (OR) from those with low or normal OR as assessed by AFC, whereas only the estradiol response could differentiate those with low AFC. GAST-stimulated serum levels of 17-OHP were also correlated with ovarian response to FSH. Using receiver operating characteristic curve analysis, stimulated 17-OHP levels were predictive of the ovarian response to controlled ovarian stimulation, with similar power to that observed with AFC but lower power than with anti-Müllerian hormone. CONCLUSIONS Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP.

“Empty follicle syndrome” after human error: pregnancy obtained after repeated oocyte retrieval in a gonadotropin-releasing hormone antagonist cycle

OBJECTIVE To report a case of empty follicle syndrome (EFS) after human error occurring in hCG administration and discuss the specific management of this event in a GnRH antagonist cycle. DESIGN Case report. SETTING A university hospital. PATIENT(S) A 27-year-old woman admitted for a first oocyte retrieval resulting in empty follicle syndrome. The cause was the lack of administration of hCG injection 36 hours earlier. MAIN OUTCOME MEASURE(S) Serial measurements of hCG, LH, and P. RESULT(S) Because no injection of GnRH antagonist had been given for 2 days, the occurrence of endogenous LH surge was assessed by measurement of serum LH, P, and E(2). In the absence of any spontaneous LH surge, EFS was successfully treated by administering 250 microg of recombinant hCG in the evening of the first failed ovarian puncture and rescheduling the second oocyte retrieval 36 hours later. Four oocytes were retrieved and two resulting embryos were transferred. Pregnancy was obtained and patient gave birth to a healthy male baby at term. CONCLUSION(S) Our case is the first report of pregnancy obtained after a successful treatment of EFS in a GnRH antagonist cycle. In contrast to GnRH agonist down-regulated cycles, the management of EFS in GnRH antagonist cycles has to take into account the possible occurrence of spontaneous endogenous LH surge.

Place des inductions de l’ovulation

L’induction d’ovulation, qu’elle serve à traiter un trouble de l’ovulation ou à améliorer la fertilité de femmes normalement ovulatoires, est l’un des traitements de l’infertilité le plus pratiqué. Cependant, c’est aussi un des traitements pour lequel on manque le plus de données concernant les pratiques et les résultats du fait, d’une part, de la multiplicité des médecins pratiquant ce type de traitement (du généraliste au gynécologue-obstétricien) et, d’autre part, du fait qu’il n’existe pas de recueil des données comme pour l’AMP. Il se vend en France environ 2,4 millions de comprimés de citrate de clomiphène par an, soit à raison de 10 cp/cycle, 240 000 cycles de traitement chaque année. Pour les gonadotrophines, l’évaluation est encore plus délicate. Les ventes annuelles représentent 4 380 000 d’équivalents (eq) 75 UI. La part utilisée pour les 50 000 cycles annuels de FIV/ICSI est estimée à 55 %. Il faut en plus déduire 55 000 cycles d’insémination (IIU) et 14 000 cycles de transfert d’embryon congelé (dont seulement une partie est réalisée avec stimulation). En faisant une estimation du nombre d’eq 75 UI utilisés par cycle, le différentiel revenant à l’induction d’ovulation hors AMP représenterait entre 50 000 et 100 000 cycles. Au total, l’induction d’ovulation hors AMP représenterait donc environ 300 000 cycles par an. La mise en route d’une induction d’ovulation nécessite la réalisation préalable d’un bilan complet de l’infertilité du couple comprenant au minimum l’évaluation de la perméabilité tubaire, des caractéristiques du sperme et bien entendu le diagnostic positif et étiologique d’un éventuel trouble de l’ovulation. Les troubles de l’ovulation sont une cause fréquente d’infertilité et représentent environ 30 % des causes d’infertilité féminine. Il est très important d’avoir évalué le statut ovulatoire de la patiente afin de choisir le traitement inducteur le plus adapté.Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 38 - N° S1 - p. F26-F34