High doses of GnRH antagonists are efficient in the management of severe ovarian hyperstimulation syndrome.

OBJECTIVE: To determine whether treatment of severe ovarian hyperstimulation syndrome (OHSS) with high-dose gonadotropin-releasing hormone (GnRH) antagonist, due to its luteolytic effect, is an effective method of management. METHODS: Six infertile patients who had been scheduled for embryo transfer and developed early-onset severe OHSS with ascites and hemoconcentration were chosen for treatment with 3.0 mg of a GnRH antagonist (Cetrotide; Cetrorelix, Serono, Madrid, Spain). The response of these patients was compared with five patients with severe early-onset OHSS who received support therapy alone. All patients were evaluated clinically, echographically, and hematologically. RESULTS: Estradiol (E2) levels dropped significantly a few days after treatment. Peritoneal fluid regression measured by ultrasound was faster on the study group compared with controls. Hematocrit remained comparable in both groups during follow-up. In two cases a second bolus of GnRH-antagonist was used due to clinical and biochemical findings during the four days of observation following the initial dose. None of the patients treated with GnRH antagonists required paracentesis. CONCLUSIONS: Treatment with high doses of GnRH antagonists seems to be effective in the management of severe OHSS.

Early detection of embryonic malformations by transvaginal and color Doppler sonography.

A total of 834 women with uneventful pregnancies were followed prospectively until the 15th week of gestation by TVS to screen for early embryonic malformations. Twenty-eight embryonic anomalies were detected in this series (3.3%). The median gestational age at diagnosis was 11 (range, 8 to 15) weeks. Two neural tube defects were missed by early TVS screening. Two suspected abdominal wall defects were not confirmed by repeat mid-second trimester abdominal sonography representing 6.7% of all fetal malformations evident by 24 weeks of gestation. The sensitivity and specificity of TVS screening for fetal malformations in this series were 93.3 and 99.7%, respectively. In addition, the role of TCDU also was investigated in these 28 abnormal embryos. TCDU proved to be of limited value as it was useful only for evaluating those embryonic malformations with vascular involvement. In such cases, the diagnosis was greatly enhanced with this technique. Two previously undetected single umbilical arteries were also diagnosed by TCDU as well. This series included 11 aneuploid embryos (44%), most of them among the embryos with focal or generalized edema. This study demonstrates that screening for early embryonic malformations is feasible using TVS techniques, but a repeat mid-second trimester abdominal sonogram still is recommended.

Aetiological factors involved in the low response to gonadotrophins in infertile women with normal basal serum follicle stimulating hormone levels.

This study was designed to investigate possible aetiological factors involved in the low response to gonadotrophins in women with normal basal serum follicle stimulating hormone (FSH) concentrations, stimulated for assisted reproduction. Nine of these patients with normal basal serum FSH and 22 normal controls (five of whom had had a normal response to previous gonadotrophin stimulation) were prospectively subjected to: (i) transvaginal pulsed colour Doppler ultrasound evaluation of the vessels surrounding the dominant follicle for blood flow impedance analysis, (ii) the clonidine test to explore the ability of the pituitary to release growth hormone, and (iii) detection of anti-granulosa cell auto-antibodies in blood using an enzyme-linked immunosorbent assay (ELISA). The pulsatility and resistance indices (PI, RI) were significantly (P < 0.01) higher in the women with low responses as compared to the controls on days -1 and 0 (day 0 = ovulation). Seven out of the nine low responders were out of the range calculated for normal values after evaluation of the controls. A significant (P < 0.05) decrease in the secretion of growth hormone 60-90 min after clonidine ingestion was observed in the low responders as compared to five controls with previous normal response to ovarian stimulation. Six out of the nine low responders showed a negative clonidine test. No increase in anti-granulosa cell auto-antibodies was observed in the low responders as compared to the controls, including normal responders. In conclusion, an abnormal follicular blood flow impedance in the natural cycle may be related to low responses to gonadotrophins in patients with normal serum FSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical localization of filaggrin in benign, premalignant and malignant cervical tissue.

Epithelial distribution of filaggrin, a histidine-rich protein related to squamous terminal differentiation, was investigated in 87 cervical biopsies using an avidin-biotin-peroxidase technique with a monoclonal anti-human filaggrin antibody (AKH1). Normal squamous cervical epithelium exhibited a positive homogeneous immunoperoxidase stain in the upper parabasal, intermediate and superficial cell layers. Similar findings were obtained in cervical condylomas, although full-thickness staining was observed in 35.7% of the cases (P < 0.001). Filaggrin expression in CIN was inversely related to the severity of the lesion (P < 0.001). An irregular staining pattern was present in most high-grade CIN. Filaggrin expression was closely connected to the degree of tumour differentiation (P < 0.05) in squamous cell carcinomas of the cervix. Abnormal filaggrin stainings identified a premalignant/malignant cervical squamous lesion with a positive predictive value of 92.3%. Non-squamous epithelia showed lack of filaggrin expression. Filaggrin may therefore be considered a marker of squamous differentiation in both the normal and pathological human uterine cervix.

In vitro fertilization as a diagnostic and therapeutic tool in a patient with partial 17,20-desmolase deficiency.

OBJECTIVE: To present a case with 17,20-desmolase activity deficiency in which in vitro fertilization (IVF) served not only as a therapeutic approach but also as a diagnostic tool for the specificity of the enzymatic deficiency. DESIGN: IVF in the patient under study compared with a control group. All women treated with pure follicle-stimulating hormone (FSH). SETTING: IVF program at the Instituto Valenciano de Infertilidad. PATIENTS, PARTICIPANTS: A patient with primary amenorrhea, who was the subject under study, and seven normally cycling control patients undergoing IVF in the same series. INTERVENTIONS: IVF, steroidogenesis in vitro of granulosa-luteal cell obtained at ovum pick-up. MAIN OUTCOME MEASURE(S): Oocyte fertilization and embryo cleavage. Serum and follicular fluid (FF) levels of estradiol (E2), progesterone (P), testosterone (T), androstendione (A), 17 alpha-hydroxyprogesterone (17-OHP). In vitro accumulation of E2 and P. RESULTS: Ovulation induction with FSH was successful in achieving follicular development despite low circulating E2. Fertilization and cleavage rates were similar to the control subjects. The patient developed ovarian hyperstimulation. The lack of 17,20-desmolase activity was detected by normal P levels in serum and FF, high 17-OHP, and low T, A, and E2 levels in serum and FF. Granulosaluteal cell cultures in the presence of T restored normal E2 and P production in response to gonadotropins. CONCLUSIONS: In patients with 17,20-desmolase deficiency, follicular development, oocyte maturation, and fertilization can take place in a low estrogenic environment.

Progesterone versus dehydrogesterone as replacement therapy in women with premature ovarian failure.

Dehydrogesterone (DH) induces normal endometrial secretory patterns in infertile as well as post-menopausal women, and has been successfully employed in the treatment of luteal-phase defects. The purpose of this study was to compare DH and progesterone (P) as progestins in steroid replacement cycles in eight women with premature ovarian failure (POF). Patients were treated during two subsequent cycles. Oestradiol valerate was used as the oestrogen. Four women received P as progestin in the first treatment cycle, while the remaining four patients began with DH. Histological dating and total protein content of uterine fluids (PCUF) were used as markers of P action on the endometrium. Samples were obtained on days 18-19 (early luteal phase, ELP) and day 26 of each cycle. Five regularly cycling women served as control for the normal range of PCUF. Histological dating of the endometrium showed ELP out-of-phase glands in 37.5% of cases treated with DH in comparison to none in the P group. Moreover, a characteristic ELP stromal haemorrhagic suffusion and increased oedema were present at the surface of the endometrium in all cases treated with DH. There was no histological difference between treatments on day 26 of the cycle. A significant (P less than 0.05) decrease in PCUF was observed in DH-treated endometria in comparison to P-treated endometria and controls. All three cases dated as out-of-phase endometria in the ELP had a PCUF less than or equal to 0.5 mg/ml. There was no difference between groups in PCUF on day 26. In conclusion, the morphological and biochemical data suggest that the endometrium supplemented with DH in women with POF fails to present optimal conditions for implantation of human embryos in the ELP. It is recommended that oral DH should not replace i.m. P as the progestin in steroid replacement cycles.