Circulating procoagulant microparticles in women with unexplained pregnancy loss: a new insight.

One of the frequently proposed mechanisms for pregnancy losses refers to uteroplacental thrombosis. However the contribution of classical thrombotic risk factors remains questionable and, if real, does not account for a large number of pregnancy losses. The aim of this study was to investigate the presence of circulating procoagulant microparticles, a new marker of cell activation already associated with various prothrombotic clinical settings. Microparticles were assessed by an original prothrombinase assay on platelet depleted plasma obtained from 74 women with a history of pregnancy loss without apparent cause and 50 controls. Patients were studied at least 2 months after the last obstetrical event and were classified into 2 groups: 49 women with at least 3 consecutive spontaneous abortions at or before the 10th postmenstrual week and 25 with at least one fetal death beyond the 10th postmenstrual week. Among the 74 patients, 41 had increased levels of circulating microparticles, 29 belonging to the group of early pregnancy loss (59%) and 12 to the group of late pregnancy loss (48%). The high prevalence of increased levels of procoagulant microparticles in both groups makes this new marker very promising for the understanding, follow up and therapeutical handling of pregnancy loss.

GnRH antagonist in single-dose applications.

Previous studies on ovarian stimulation have confirmed the efficacy of a single dose of the gonadotrophin-releasing hormone (GnRH) antagonist, Cetrorelix, in preventing premature LH surges. The single-dose protocol is easy to use and assures patient compliance. When compared with the long protocol using a depot administration of the GnRH agonist, triptorelin, the IVF results in patients treated with Cetrorelix showed a shorter treatment duration, reduced amount of human menopausal gonadotrophin (HMG) required and a lower occurrence of ovarian hyperstimulation syndrome (OHSS). The pregnancy rates did not differ significantly between the two treatments. The use of Cetrorelix in natural cycles associated with gonadotrophins reduced the rate of premature LH surges and, therefore, the cancellation rate. The stimulation was minimal and the preliminary pregnancy rates were satisfactory. If a larger study confirms the results of the natural cycle with HMG support, the single-dose administration of GnRH antagonist could represent an interesting first-choice IVF treatment in selected indications. The tolerance of Cetrorelix was excellent in all patients, with only mild and transitory reactions at the injection site. New GnRH antagonists are already available for clinical use in some countries, and they will certainly change ovarian stimulation protocols. If the pregnancy rates are confirmed, the main advantages of these new compounds are the reduction in side-effects and complications of the stimulation protocol; a clear benefit to the patients.

Hysteroscopic treatment of severe Asherman's syndrome and subsequent fertility.

In a retrospective case report series, we evaluated the efficacy of hysteroscopic adhesiolysis in patients with severe Asherman's syndrome. In 31 patients with permanent severe adhesions, hysteroscopic treatment was performed. In all patients, uterine cavity with at least one free ostial area was restored after one (n = 16), two (n = 7), three (n = 7), and four (n = 1) surgical procedures. All previously amenorrhoeic patients (n = 16) had resumption of menses. Twenty-eight patients were followed-up with a mean time of 31 months (range 2-84). Fifteen pregnancies were obtained in 12 patients and the outcomes were the following: two first trimester missed abortions, three second trimester fetal losses, one second trimester termination of pregnancy for multiple fetal abnormalities and nine live births in nine different patients. Pregnancy rate after treatment was 12/28 (42.8%) and live birth rate was 9/28 (32.1%). In patients 35 years (P = 0. 01). Three patients were lost to follow-up and their results omitted. In nine patients with live births, one Caesarean hysterectomy for placenta accreta and one hypogastric arteries ligation for severe haemorrhage and placenta accreta were performed. Hysteroscopic treatment of severe Asherman's syndrome appeared to be effective for the reconstruction of a functional uterine cavity with a 42.8% pregnancy rate. However, these pregnancies were at risk for haemorrhage with abnormal placentation.

Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation.

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.

A spontaneous and severe hyperstimulation of the ovaries revealing a gonadotroph adenoma.

We report an unusual case of a gonadotroph adenoma in a 34-yr-old woman, revealed by a dramatic rise in the plasma estradiol (E2) concentration (26,800 pmol/L; normal, <370), with nonsuppressed FSH and LH levels (4.9 and 2.4 mIU/mL, respectively). The PRL level was 503 ng/mL. The testosterone and progesterone levels were 7 and 17 nmol/L, respectively. The levels of inhibin alpha, inhibin A, and inhibin B were increased compared to normal values in both the follicular (fp) and luteal (lp) phases of the menstrual cycle [inhibin alpha, 1986 IU/L (fp normal, <700; lp normal, <1650); inhibin A, 254 pg/mL (fp normal, <20; lp normal, <120); inhibin B, 246 pg/mL (fp normal, <150; lp normal, <30 lp)]. Pituitary magnetic resonance imaging revealed a huge pituitary adenoma. After transphenoidal surgery, the patient presented with pituitary insufficiency and diabetes insipidus. RT-PCR of the tumor tissue was positive for LHbeta, FSHbeta, alpha-subunit, and PRL. This case is of particular interest because 1) although the E2 level was extremely high, the patient did not present with ascitis, suggesting that chronic elevated E2 does not play a crucial role in the hyperstimulation symptoms; 2) the extreme rise in E2 was related to the cosecretion of FSH and LH, confirming the two-cell two-gonadotropin theory; and 3) the rise in inhibin B is associated with FSH secretion, whereas the rise in inhibin A is probably due to luteinization.

[Contraceptive use in female transplant recipients]. / La contraception chez la femme transplantée.

The choice of a good contraception is difficult in allograft recipient woman. Even if patients recovered a normal menstruation and fertility, the oral and the intra-uterine devices contraceptives are contraindicated. If pregnancy occur too soon after the transplantation, the survival graft is in danger. According to the literature, 50% allograft recipient have begun a pregnancy without medical concentration. In this article, we wanted to find the contraceptive method effective and appropriate in recent allograft recipient female according to the organ grafted. We discuss the new contraceptive methods and advise to avoid, in first instance a tubal ligature.

[Results of oocyte donation in women with different indications, ages and therapeutic strategies]. / L'analyse des résultats du don d'ovocyte en fonction de l'indication, de l'âge et de la stratégie thérapeutique.

PURPOSE: Compare the effectiveness of oocyte donation for various indications, ages and treatments. METHODS: Retrospective analysis of 319 transfers for 184 couples (243 with fresh embryos and 76 with frozen embryos). Transfers are divided into: -7 groups according to indication: premature ovarian failure (POF) with normal caryotype n = 122, surgical POF n = 26, postchemotherapy and postradiation therapy POF n = 23, genetic disease carrier n = 11, IVF failure n = 69, primary amenorrhea n = 58, POF with abnormal caryotype n = 10. -2 groups according to the recipient's age (Group I < or = 40 years, Group II > 40 years); -3 groups according to the dose and the mode of administration of the treatment. Oocytes were donated by volunteer donors of less than 38 years having at last one child. RESULT: According to the recipient's age 31.3% clinical pregnancies (CP) and 24.2% ongoing pregnancies (OP) for group I, versus 19.4% CP and 11.9% OP for group II. The results according to the indication were similar except for postchemotherapy and postradiation therapy POF for which the rate of CP as well as the rate of OP were particularly low. For the treatment groups there is a significant reduction of CP and OP as the treatment dose increases. CONCLUSION: The recipient's age plays an important role for the development of pregnancy and this shows that apparently uterine ageing also plays an undeniable role for the decline of female fertility. Increasing doses of estradiol reduces the rate of CP and OP. Postchemotherapy and postradition therapy POF has much lower results than other indications.

[Tumor necrosis factor and induced labor]. / TNF et déclenchement du travail.

TNF and LPS can induced labour in mice. In our serial, in induced RU 486 labour, TNF value enhanced 48 hours after RU 486 and decreased after parturition.