High Risk Of Ovarian Hyperstimulation Syndrome Research Articles

Subpopulations of human granulosa-luteal cells obtained during early timed and during normally timed follicular aspiration in in-vitro fertilization-embryo transfer cycles

Objective: To find the differences between human granulosa-luteal cells obtained during early timed follicular aspiration to prevent severe ovarian hyperstimulation syndrome (OHSS) and during normally timed follicular aspiration. Design: Retrospective analysis of clinical laboratory data. Setting: In vitro fertilization unit, University Department of Obstetrics and Gynecology, Ljubljana, Slovenia. Patient(s): Twenty women undergoing IVF-ET at high risk for OHSS. Intervention(s): Cells were obtained from the follicles of women who were stimulated with hMG and hCG during an early timed follicular aspiration of one ovary, 10–12 hours after hCG, and during a normally timed follicular aspiration of the contralateral ovary, 32–36 hours after hCG administration. Main Outcome Measure(s): Subpopulations of granulosa-luteal cells were observed by computerized image analysis in which hCG was localized using immunoperoxidase staining. Result(s): Early timed follicular aspirates contained no oocytes and only a scant number of granulosa cells. Granulosa-luteal cells were smaller than those from normally timed follicular aspirates. We identified three subpopulations in early timed follicular aspirates: nonluteinized, small luteinized, and medium luteinized cells. In normally timed follicular aspirates, four subpopulations were identified, including large luteinized cells. The normally timed follicular aspirates contained more hCG-stained cells. Three staining types of hCG localization were found: on the surface membrane, on the surface membrane and within the cytoplasm, and only within the cytoplasm of cells from normally timed follicular aspirates. Early timed follicular aspirates contained only cells with membrane hCG localization. Conclusion(s): We found differences in morphometric characteristics and hCG localization between human granulosa-luteal cells obtained during early timed follicular aspiration to prevent severe OHSS and during normally timed follicular aspiration.

Vascular Permeability Factor and Vascular Endothelial Growth Factor in Ovarian Hyperstimulation Syndrome

Objective To determine whether serum levels of vascular permeability factor (VPF) are elevated in patients with ovarian hyperstimulation syndrome (OHSS) and to determine if luteinizing granulosa cells may be a source of VPF. Design Prospective observational study. Setting University IVF and GIFT program. Patients Eight consecutive IVF and GIFT patients at high risk for OHSS. Main Outcome Measures Vascular permeability factor concentration in serum and follicular fluid. Results Serum VPF was significantly higher (15.2 ± 4.0 pM; mean ± SEM) on day +14 in the group who developed severe OHSS compared with those who did not. Follicular fluid VPF (171.5 ± 18.5 pM) was approximately 100-fold greater than serum (1.7 ± 1.3 pM) or peritoneal fluid (2.5 ± 1.3 pM) 36 hours after hCG administration. Conclusion Vascular permeability factor is elevated in patients with severe OHSS and the ovary may be a source of VPF secretion.

Steroidogenesis of cultured granulosa cells in women at risk for ovarian hyperstimulation syndrome

To determine if cultured human granulosa cells (GCs) obtained from women at risk for ovarian hyperstimulation syndrome (OHSS) possess altered steroidogenic capacity. Prospective analysis of 28 consecutive in vitro fertilization-gamete intrafallopian transfer (IVF-GIFT) cycles. In Vitro Fertilization Program at Rush Presbyterian St. Luke's Medical Center in Chicago, Illinois. Eighteen patients (group I) with serum estradiol (E2) levels > 7,342 pmol/L on the day of exogenous human chorionic gonadotropin (hCG) administration (day 0) with > 10 ovarian follicles present (high risk for OHSS); 10 patients (group II) with E2 < or = 7,342 pmol/L on day 0 and < or = 10 follicles. Human GCs obtained during gonadotropin-releasing hormone agonist-pretreated IVF-GIFT cycles were cultured in the absence (control) or presence (hCG) of hCG, 1 IU/mL, and/or androstenedione (A) 10(-7) M. Granulosa cells obtained from follicles < or = 15 mm diameter were cultured separately from those obtained from follicles > 15 mm diameter. Estradiol (E2) and progesterone were measured in tissue-culture medium by a solid-phase direct radioimmunoassay. In vitro E2 production by cultured GCs was significantly increased in follicles < or = 15 mm diameter from women considered at risk of developing OHSS (group I). Estradiol response to hCG and/or A appeared enhanced in all follicles in group I. Progesterone production in the basal and hCG challenged state was greater in cells obtained from large follicles in group I than in group II. Ovarian hyperstimulation syndrome appears to be a function of an increased number of follicles that express an enhanced steroidogenic capacity.

Ovarian hyperstimulation syndrome after superovulation using GnRH agonists for IVF and related procedures.

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of ovarian stimulation. In severe cases, haemoconcentration, hypovolaemia, thromboembolism and death may result. It is reassuring that its incidence is not increased after ovarian stimulation for in-vitro fertilization despite very high serum oestradiol levels and large numbers of follicles and oocytes. This may be related to follicular aspiration, expert monitoring or low implantation rates. However, complete prevention has not been achieved despite the wide availability of ultrasound and oestradiol assays, thus presenting the clinician with a continuous challenge. Our aim is to analyse critically the most recent published series of OHSS in in-vitro fertilization and other assisted reproduction techniques using stimulation with gonadotrophin releasing hormone agonists (GnRHa) and human menopausal gonadotrophin (HMG). The main determining factor in the development of OHSS appears to be ovarian predisposition. Patients with polycystic ovarian disease are at a high risk of OHSS and therefore a small dose and slow start of HMG is recommended, tailoring the dosage according to the ovarian response. Accurate prediction by ultrasound and oestradiol assays and strict prevention by withholding human chorionic gonadotrophin (HCG) or cryopreservation of all the embryos have a major impact on the occurrence of OHSS. It is interesting that fixed-schedule IVF cycles, without detailed monitoring, are not associated with an increased incidence of OHSS. The use of GnRHa, despite expectations, is associated with a higher prevalence of OHSS. Luteal phase supplementation with progesterone rather than HCG should be used in cycles where oestradiol is greater than 2500 ng/l or where the number of oocytes exceeded 10.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe ovarian hyperstimulation syndrome using agonists of gonadotropin-releasing hormone for in vitro fertilization: a European series and a proposal for prevention

Severe ovarian hyperstimulation syndrome (OHSS) was recorded in 8 of 413 patients after the use of gonadotropin-releasing hormone agonists (GnRH-a) associated with gonadotropins for in vitro fertilization. Seven of the 8 patients were pregnant. Common factors associated with the development of OHSS were high serum estradiol values on the day of ovulation induction and many follicles greater than or equal to 12 mm. Based on this experience, a new therapeutic schedule was used in a group of 10 patients who, after GnRH-a and gonadotropin stimulation, were judged to be at high risk of OHSS on the day of human chorionic gonadotropin (hCG). No hCG was administered and gonadotropins were stopped. The administration of GnRH-a was continued and, after a further period of pituitary desensitization, follicular stimulation was recommended with a lower dose of gonadotropins. No cases of OHSS occurred and 3 patients became pregnant.