J.M. Weiss

Luteal phase support using either Crinone® 8% or Utrogest®: results of a prospective, randomized study

The Crinone 8% preparation makes it possible to administer natural progesterone (90 mg) vaginally once daily for luteal phase support (LPS). Until now, no prospective, randomized studies have directly compared this new preparation with widely used Utrogest capsules, which were originally designed for oral administration but are used routinely as a vaginal preparation. A prospective, randomized study investigated 126 patients undergoing cycles of in vitro fertilization (IVF) and IVF/intracytoplasmic sperm injection (ICSI). Patients received either Crinone 8% (n = 73) vaginally once daily or two Utrogest capsules (n=53) vaginally three times daily (600 mg). Clinical pregnancy rates were comparable (28.8 versus 18.9%), as were clinical abortion rates until 12 weeks of gestation (14.3 versus 10.0%) and clinical ongoing pregnancy rates (24.7 versus 17.0%) in the Crinone 8% and Utrogest groups, respectively. Forty-seven non-pregnant patients were randomly selected to answer questions regarding comfort during LPS. Crinone 8% had a clear advantage over Utrogest as it resulted in less vaginal discharge (P < 0.01) and fewer application difficulties (P<0.05). Twenty patients familiar with the alternative preparation from a previous cycle also noted that Crinone 8% was easier to apply (P < 0.01) and less time consuming (P < 0.05) to use than Utrogest.

Insulin resistance in patients with polycystic ovary syndrome

With a prevalence of 5%–10% the polycystic ovary syndrome (PCOS) is an exceptionally common disorder of premenopausal women. According to prospective studies, women with PCOS present abnormal glucose tolerance and diabetes mellitus in 31%–35% and 7.5%–10%, respectively. PCOS patients have a higher prevalence of cardiovascular risk factors such as hypertension, type 2 diabetes and dyslipidaemia. The rate of spontaneous abortions as well as the risk to develop gestational or type 2 diabetes is increased in PCOS. Therefore, PCOS is not only a reproductive problem but a complex endocrine disease with important health implications. The role of the glucose metabolism in PCOS, the health consequences and possible interventions are reviewed in this article.

Distribution of persistent organochlorine contaminants in infertile patients from Tanzania and Germany

AbstractPurpose: To test whether environmental pollutants could affect fertility in humans. Methods: 31 women and 16 men from Tanzania and 21 couples from Germany were included (n=89). Pesticides and polychlorinated biphenyls were measured in serum, follicular fluid or seminal plasma by gaschromatography and related to sperm quality and pregnancy rates. Results: Higher concentrations of DDT+DDE and dieldrin in Tanzania and higher concentrations of PCBs in Germany and in men were detected. All compounds showed higher concentrations in serum and lowest concentrations in seminal plasma. A lower pregnancy rate in German women with high serum concentrations of DDT+DDE was observed. The toxins had no impact on sperm quality. Conclusions: The distribution of toxins between agricultural and industrial countries is different. Seminal plasma seems to be inert against chemicals. In patients with high serum concentrations of DDT and DDE pregnancy rates were impaired.

Retiform hemangioendothelioma: Another tumor associated with human herpesvirus type 8?

Retiform hemangioendothelioma is a rare low-grade angiosarcoma of the skin. It shares some clinical characteristics with Kaposis sarcoma, a tumor with known human herpesvirus 8 (HHV-8) association. We report a case of retiform hemangioendothelioma in which we detected HHV-8 DNA sequences.

Counselling on cryopreservation of pronucleated oocytes

The German Embryo Protection Law permits only the cryopreservation of supernumerary pronuclear stage eggs. Data are needed to counsel patients about their individual benefits from this procedure. All fresh embryo transfer cycles performed from January 1994 until December 1998 in which supernumerary pronucleate eggs were cryopreserved (n = 557) were analysed retrospectively, together with data from all subsequent cycles involving transfers of frozen-thawed pronucleate eggs (n = 420) from January 1994 until June 2001. The additional cumulative pregnancy rate per fresh cycle was 11.5%. This rate depended on the number of embryos per transfer, i.e. 1.9, 8.2 and 13.0% respectively when one, two or three embryos were transferred (P < 0.05). A strong correlation was found between the numbers of cryopreserved pronucleate eggs and pregnancy rates, of 9.3, 10.5 and 17.1% when 1-3, 4-6, or at least 7 pronucleate eggs were available respectively. Additional benefit in terms of this rate from cryopreservation for a patient with and without a pregnancy in the fresh embryo transfer cycles was 5.3 and 12.7% respectively. It is concluded that higher pregnancy rates in cycles involving cryopreserved eggs for patients who did not become pregnant in fresh transfer cycles reveals the disadvantage of the German Embryo Protection Law, which does not allow embryo selection. Therefore, cryopreservation of pronucleate eggs with a higher developmental potential is possible. The total pregnancy rate could be raised from 28.0 to 35.5% per fresh transfer cycle.

Gonadotrophin-releasing hormone (GnRH) and GnRH agonists: mechanisms of action

The hypothalamic decapeptide gonadotrophin-releasing hormone (GnRH) binds to specific receptors on pituitary gonadotrophs. These receptors belong to the family of G protein-coupled receptors. Their activation leads to phosphoinositide breakdown with generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol. These second messengers initiate Ca2+ release from intracellular stores and activation of protein kinase C, both of which are important for gonadotrophin secretion and synthesis. Prolonged activation of GnRH receptors by GnRH leads to desensitization and consequently to suppressed gonadotrophin secretion. This is the primary mechanism of action of agonistic GnRH analogues. By contrast, GnRH antagonists compete with GnRH for receptors on gonadotroph cell membranes, inhibit GnRH-induced signal transduction and consequently gonadotrophin secretion. These compounds are free of agonistic actions, which might be beneficial in certain clinical applications.

Patients undergoing frozen-thawed embryo transfer have similar live birth rates in spontaneous and artificial cycles

PurposeTo evaluate the outcome of frozen-thawed embryo transfer (FET) when freezing takes place at the pronuclear stage, a retrospective analysis was performed comparing spontaneous and artificial cycles.Methods148 women received FET in a spontaneous cycle (Group A) and 55 women received FET in an artificial cycle (Group B) induced by administering estrogen (E2) and progesterone (P). Pregnancy rates, endometrial thickness and serum levels of E2, P and luteinizing hormone (LH) were measured. Statistical analysis included the mean, the standard deviation, the Chi-squared test and the T-test.ResultsThe clinical pregnancy rate was 34.5% for Group A and 21.8% for Group B (p = 0.084), with a live birth rate of 20.9% and 12.7% respectively (p = 0.15). There was no difference in endometrial thickness or the P levels, while LH and E2 levels were significantly higher in group B (p < 0.0001).ConclusionOur retrospective study shows a trend towards higher pregnancy rates and live birth rates with the administration of FET during a spontaneous cycle compared to FET during an artificial cycle. Large randomized controlled trials are needed to confirm this trend.

Metformin, naltrexone, or the combination of prednisolone and antiandrogenic oral contraceptives as first-line therapy in hyperinsulinemic women with polycystic ovary syndrome

To compare the short-term effects of metformin (M), naltrexone (N), and a combination of OC and prednisolone (OC/Pr) on the metabolic state and the ovarian function of PCOS women, we randomized 29 women to a 3-month course of therapy. We observed significant improvements in hyperandrogenemia and ovulation rates in PCOS women of all three groups, in the absence of changes in the metabolic state, suggesting that insulin resistance in PCOS patients is only one of several factors leading to hyperandrogenemic ovarian failure.

Effect of the gonadotropin-releasing hormone antagonist ganirelix on cyclic adenosine monophosphate accumulation of human granulosa-lutein cells

OBJECTIVE To evaluate whether the GnRH antagonist ganirelix exerts an effect on cyclic adenosine monophosphate (cAMP) production of human granulosa-lutein (GL) cells in vitro. DESIGN In vitro cell culture study. SETTING Research laboratory of a university hospital. PATIENT(S) Mural GL and cumulus cells were obtained from 15 patients on whom controlled ovarian hyperstimulation was being performed for intracytoplasmic sperm injection treatment. INTERVENTION(S) Mural GL and cumulus cells were cultured for 48 hours with and without 1 nM ganirelix or triptorelin. For the last 6 hours, the cells were either exposed to 1-5 IU hCG or left unstimulated. MAIN OUTCOME MEASURE(S) At the end of the culturing period, the intracellular and extracellular cAMP accumulations were measured by an (125)I-scintillation proximity assay. RESULT(S) hCG induced dose-dependent increases in total cAMP accumulation. Stimulation with 1 IU/mL hCG resulted in 9-fold and 13-fold increases, and 5 IU/mL hCG resulted in 19-fold and 14-fold increases in total cAMP release from cumulus and mural GL cells, respectively. On the other hand, treatments with 1 nM GnRH antagonist ganirelix and 1 nM GnRH agonist triptorelin did not exert any significant changes on the basal and hCG-stimulated cAMP accumulation of mural GL cells and cumulus cells as compared with controls. CONCLUSION(S) Ganirelix does not influence basal and hCG-stimulated cAMP accumulation of human GL cells in vitro. cAMP is apparently not involved in the mechanism of action of GnRH analogs in human ovary.

Preparation of cycles for cryopreservation transfers using estradiol patches and Crinone® 8% vaginal gel is effective and does not need any monitoring

Supernumary pronucleated stage oocytes (PN) can be cryopreserved and later transferred in spontaneous, stimulated or artificial cycles. In this study, we re-evaluated 342 artificial cycles with a transdermal estradiol release system (Estraderm TTS 100) in combination with a vaginal progesterone delivery system (Crinone 8%). Endometrial thickness and serum estradiol on day 14 were correlated with clinical and ongoing pregnancy rates. Endometrial thickness between 7 and 15 mm did not relate to significantly different pregnancy rates. The estradiol serum level did not predict success. In conclusion, this method of endometrial preparation is comfortable for patients and monitoring is unnecessary.