Use of a luteal estradiol patch and a gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation for in vitro fertilization in poor responders.

The administration of a luteal E2 patch/GnRH antagonist protocol before gonadotropins in poor responders may improve ovarian stimulation and result in greater uniformity in follicular development and improved pregnancy rates.

Taking a basal follicle-stimulating hormone history is essential before initiating in vitro fertilization.

OBJECTIVE: To analyze IVF outcomes in patients with a history of one or more elevations in basal FSH who have a normal basal FSH at the start of their IVF cycle, compared with the general IVF population. DESIGN: Retrospective clinical study. SETTING: University hospital. PATIENT(S): General IVF patient population. INTERVENTION(S): Patients received standard IVF gonadotropin protocols, oocyte retrieval, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocyte yield, fertilization, implantation, clinical pregnancy, and cancellation rate. RESULT(S): Oocyte yields were lower in patients with a history of elevated basal FSH, for all age groups, and showed an age-dependent decline in all patients. Over the age of 40 years, both implantation and clinical pregnancy rates were lower in these patients, with no significant difference observed in patients under the age of 40 years. No pregnancies were observed in patients with a history of three or more elevated FSH levels, regardless of age. CONCLUSION(S): A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles with normal basal FSH levels but does not translate to either lower pregnancy or implantation rates. Patients aged >40 years with prior elevations in basal FSH levels have both compromised ovarian response and compromised embryo quality relative to those with normal FSH levels, as illustrated by lower oocyte yield, higher cancellation rates, and lower implantation and pregnancy rates.

Spontaneous ovarian hyperstimulation caused by a follicle-stimulating hormone-secreting pituitary adenoma.

OBJECTIVE: To report a case of spontaneous ovarian hyperstimulation resulting from an FSH-secreting pituitary adenoma. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 29-year-old previously healthy, nulligravid woman. INTERVENTION(S): Transphenoidal resection of the adenoma. MAIN OUTCOME MEASURE(S): Clinical remission. RESULT(S): After transphenoidal resection of the adenoma, the patient had an uneventful postoperative recovery with complete resolution of ovarian hyperstimulation and associated symptoms. Postoperative magnetic resonance imaging demonstrated residual tumor within the cavernous sinus. CONCLUSION(S): Follicle-stimulating hormone-secreting pituitary adenoma may present as acute spontaneous ovarian hyperstimulation.

Safety and efficacy of infertility treatment after conservative management of borderline ovarian tumors: a preliminary report.

OBJECTIVE: To evaluate the safety and efficacy of infertility treatment in a group of patients after conservative management of borderline ovarian tumors. DESIGN: Retrospective study. SETTING: University IVF unit. PATIENT(S): Five patients with previous conservative treatment of borderline ovarian tumor. INTERVENTION(S): Seventeen IVF cycles. MAIN OUTCOME MEASURE(S): Recurrence, IVF outcome. RESULT(S): At the time of diagnosis, the mean age of the patients was 32.2 +/- 6.9 years. The mean time elapsed between the initial diagnosis of a borderline tumor and the performance of IVF was 42.2 months. After IVF, the mean number of oocytes retrieved was 7.9 +/- 4.0 with a mean fertilization rate of 57.1% and a mean number of 3.1 +/- 1.4 day 3 embryos transferred. Six pregnancies were achieved in three of the five patients with a pregnancy rate per retrieval of 37.5% and per transfer of 42.9%. The mean follow-up time that elapsed since the first IVF cycle was 39.2 months (range 9-78 months). One patient had three recurrences 13, 27, and 43 months after her first IVF cycle, all of which remained histologically serous borderline tumor. All patients were without evidence of disease at the time of last follow-up. CONCLUSION(S): At a mean follow-up time of 39.2 months, our results suggest that IVF may be considered for patients with conservatively treated borderline tumors. Furthermore, overall IVF success rates were very satisfactory, suggesting no perceptible negative impact of prior borderline ovarian neoplasia on pregnancy rates after IVF.

Maternal serum vascular endothelial growth factor levels in early ectopic and intrauterine pregnancies after in vitro fertilization treatment.

OBJECTIVE: To determine whether serum levels of vascular endothelial growth factor (VEGF) 11 days after a day-3 embryo transfer were predictive of outcome, in women with normal intrauterine pregnancy (IUP), first-trimester miscarriage (SAB), biochemical (BC), and ectopic pregnancy (EP) after IVF therapy. DESIGN: Retrospective analysis. SETTING: University hospital IVF unit. PATIENT(S): One hundred eight women who underwent IVF therapy and who were subsequently diagnosed with EP, BC, SAB, or a normal IUP (27 in each category). INTERVENTION(S): Serum samples were obtained at 11 days after a day-3 embryo transfer. MAIN OUTCOME MEASURE(S): Serum concentrations of VEGF, P, and beta-hCG. RESULT(S): Serum concentrations of VEGF were similar in women with BC and EP and higher than in women with normal IUP and SAB (571.8 +/- 61.8, 604.4 +/- 73.4 vs. 448.9 +/- 39.9, 461.8 +/- 39.2 pg/mL, respectively). Also, serum beta-hCG and P levels were significantly higher in women with a normal IUP and SAB. Using a cutoff concentration of >700 pg/mL for VEGF, an EP could be distinguished from an IUP (normal and SAB), with a positive predictive value of 64% and a negative predictive value of 71%. CONCLUSION(S): Elevated maternal serum levels of VEGF, as early as 11 days after embryo transfer, are associated with ectopic pregnancies after IVF.

Markedly elevated levels of inflammatory cytokines in maternal serum and peritoneal washing during arrested labor.

BACKGROUND: The role of inflammatory cytokines in the pathophysiology of arrested labor is currently unknown. We measured levels of inflammatory cytokines in maternal serum and peritoneal washings in arrested first stage of labor to assess the possible involvement of these mediators in this obstetric disorder. METHODS: This was a prospective, case-control study involving 15 women who underwent cesarean section for arrested cervical dilatation (group I), 15 controls who were operated during active labor for nonreassuring fetal heart-rate tracing (group II) and 15 controls who were operated electively (group III). Blood samples were drawn from all women shortly before the operation. The presence of peritoneal fluid was assessed and peritoneal washings were obtained during the operation. All samples were assayed for the inflammatory cytokines interleukin (IL)-1beta, IL-6, IL-8 and soluble IL-2 receptor (sIL-2R) by solid-phase enzyme-linked immunosorbent assay (ELISA). RESULTS: All women from group I and one patient (6.7%) from group II had some degree of peritoneal fluid accumulation, while none from group III had any. Serum samples from group I contained significantly higher IL-1beta, IL-6, IL-8 and IL-2R levels than both control groups. Peritoneal washings from group I contained significantly higher IL-1beta, IL-6 and IL-8 but similar IL-2R levels. CONCLUSIONS: Arrested first stage of labor is associated with peritoneal fluid accumulation and increased levels of inflammatory cytokines in both serum and peritoneal fluids. Inflammatory cytokines may therefore be involved in the pathophysiology of arrested labor.

Severe menorrhagia due to factor VII deficiency successfully treated by thermal balloon endometrial ablation.

Factor VII deficiency, a rare inherited bleeding disorder, is often complicated by menorrhagia leading to severe anemia. These women are treated by repeated blood product transfusions, various hormone preparations, and repeated endometrial curettage. Despite the high risks involved, women with refractory disease were usually advised to undergo hysterectomy. A 36-year-old patient was known to suffer from factor VII deficiency and common variable immune deficiency, and had a long history of worsening menorrhagia. As various medical therapies failed to improve her menorrhagia, and she often required curettage and blood transfusions, we offered her more definitive treatment with thermal balloon endometrial ablation. The procedure was uneventful, and during 24 months of follow-up the patient has had several events of spotting but no heavy periods. It is suggested that thermal balloon endometrial ablation is a suitable minimally invasive therapeutic option for menorrhagia in women with factor VII deficiency.

Gonadotropin-releasing hormone (GnRH)-antagonist versus GnRH-agonist in ovarian stimulation of poor responders undergoing IVF.

PURPOSE: The objective of this study was to compare the efficacy of GnRH-antagonists to GnRH-agonists in ovarian stimulation of poor responders undergoing IVF. METHODS: Retrospective analysis of our data revealed that 56 patients underwent treatment with a GnRH-agonist according to the flare-up protocol. Patients failing to achieve an ongoing pregnancy (n = 53) were subsequently treated in the next cycle with a GnRH-antagonist according to the multiple-dose protocol. Main outcome measures included the clinical pregnancy and implantation rates. RESULTS: While ovulation induction characteristics and results did not differ between the two protocols, the number of embryos transferred was significantly higher (P = 0.046) in the GnRH-antagonist than in the GnRH-agonist stimulation protocol (2.5 +/- 1.6 vs. 2.0 +/- 1.4, respectively). The clinical pregnancy and implantation rates per transfer in the GnRH-antagonist group appeared higher than in the GnRH-agonist, but did not differ statistically (26.1 and 10.7 compared with 12.2 and 5.9%, respectively). However, the ongoing pregnancy rate per transfer was statistically significantly higher (P = 0.03) in the GnRH-antagonist than in the GnRH-agonist group (23.9 vs. 7.3%, respectively). CONCLUSION: Applying GnRH-antagonists to ovarian stimulation protocols may offer new hope for IVF poor responder patients. However, further controlled randomized prospective studies with larger sample sizes are required to establish these results.

The human fetal venous system: normal embryologic, anatomic, and physiologic characteristics and developmental abnormalities.

OBJECTIVE: The introduction of high-resolution ultrasonography combined with color-coded Doppler imaging offered a breakthrough in the evaluation of the human fetal venous system, considerably enhancing our understanding of fetal venous circulation in normal physiologic conditions, as well as providing us the ability to study circulatory changes in abnormal circumstances. The purpose of this study was to describe the normal anatomic development and complex of anomalies of the human fetal venous system and to review recently published series of these anomalies. METHODS: Normal embryologic and anatomic development is described. An English language literature search of recent MEDLINE listings was performed to glean data from recently published series reporting prenatal diagnosis of the various anomalies and their associated malformations. RESULTS: Anomalies of the human fetal venous system occur sporadically, often associated with cardiac or other malformations. The pathophysiologic mechanisms leading to abnormal in utero development of the human venous system remain largely undetermined. On the basis of the type of vein involved, embryologic precursor, and etiologic correlation (primary or secondary), classification into 4 major groups is described. CONCLUSIONS: Prenatal evaluation of fetuses found to have anomalies of the venous system should include a careful search for cardiac anomalies, including pulmonary venous drainage, and a detailed anatomic survey of the umbilical, portal, hepatic, and ductal systems to determine aberrant communication and, if possible, to discover clues to systemic diseases or thromboembolic phenomena.

The role of inflammatory cytokines in Meigs' syndrome.

BACKGROUND: Inflammatory cytokines are known to induce capillary leakage and third-space fluid accumulation in numerous gynecologic and nongynecologic disorders. This study aimed to assess their role in Meigs' syndrome. CASE: Evaluation of serum, peritoneal, and pleural fluids retrieved from a patient suffering from Meigs' syndrome revealed high interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha levels. After surgical removal of the ovarian tumor and with resolution of ascites and hydrothorax, serum levels of IL-1beta, IL-6, and IL-8 declined, whereas tumor necrosis factor-alpha levels remained high. CONCLUSION: The correlation between these inflammatory cytokines and the clinical course of Meigs' syndrome suggests their involvement in the formation of ascites and hydrothorax in this disorder.

Extreme caudal agenesis. Possible drug-related etiology?

BACKGROUND: Caudal regression syndrome (CRS) is a rare anomaly of the lower body pole that represents a continuum of congenital malformations ranging from isolated sacral agenesis to absence of the lumbosacral spine and major visceral anomalies. While the exact etiology of this syndrome is unclear, maternal diabetes, genetic factors, teratogens and vascular anomalies altering blood flow have been hypothesized to play a role in its pathogenesis. CASE: A fetus had extreme hypotrophy of the caudal body pole, aplasia of the lower spine and complete renal agenesis diagnosed in the second trimester by ultrasound. Maternal history revealed the use of minoxidil solution for preventing hair loss for four years prior to and during gestation. Also, the mother had taken trimethoprim-sulfamethoxazole during the first trimester for treatment of upper respiratory disease. No maternal diabetes or history of familial genetic diseases was evident. CONCLUSION: In an extreme form of CRS consisting of complete aplasia of the lower body pole and viscera and additional malformations, a possible drug-related etiology was suggested but should be confirmed by more studies.