Paul A. Bergh

Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment.

OBJECTIVE To overview the world literature on ovarian hyperstimulation syndrome (OHSS) and modes of prevention and treatment of OHSS. STUDY SELECTION All the pertinent literature on OHSS, its prevention, and strategies for treatment were reviewed. PREVENTION Key to prevention is proper identification of the population at risk, which includes women with either the hormonal or the morphological signs of polycystic ovarian disease, high serum estradiol (E2) before human chorionic gonadotropin (hCG) administration (E2 greater than 4,000 pg/mL), multiple follicular response (greater than 35), younger age, and lean habitus. When a high risk situation is recognized, ovulatory dose of hCG may be reduced, avoided (with cycle cancellation), or substituted by gonadotropin-releasing hormone or its agonist. Luteal support with hCG is to be bypassed. To minimize risk of OHSS, endogenous pregnancy-drived hCG may be eluded by judicious cryopreservation of all embryos. Last, follicular aspiration will allow higher levels of E2 and larger number of follicles to be matured with lesser risk of OHSS than conventional ovulation induction without follicular aspiration. TREATMENT In-house for the severe and intensive care for the critical form. Meticulous fluid and electrolyte balance using both crystalloids and colloids (albumin) until hemoconcentration abates. Paracentesis is indicated for tight ascites, deteriorating kidney functions, and symptomatic relief. Diuretics may be prudently used once hemodilution is achieved. Dopamine drip may be used as a renal rescue, whereas heparin is indicated for thromboembolic phenomena and surgery reserved for abdominal catastrophies. Therapeutic interruption of an early gestation may be lifesaving when all other measures have failed. CONCLUSIONS Although severe and critical OHSS may not be completely avoided, early recognition of high-risk factors, judicious prevention schemes, and treatment strategies should reduce the complication and long-term sequelae of this iatrogenic syndrome.

Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality

OBJECTIVE To determine if premature luteinization has an adverse effect on oocyte and, hence, embryo quality. DESIGN Retrospective evaluation of anonymous ovum donors/oocyte recipients. SETTING A large oocyte donation program. PATIENTS, PARTICIPANTS Sixty-eight women undergoing controlled ovarian hyperstimulation (COH) as ovum donors were matched to 68 women with ovarian failure as ovum recipients who had endometrial maturation exogenously controlled by an identical hormone replacement protocol. INTERVENTIONS Serum was collected for E2 and P in donors and recipients. MAIN OUTCOME MEASURES The incidence of premature luteinization was determined in donors. Cycle characteristics were compared between donors with and without premature luteinization, with emphasis on oocyte and embryo quality. Implantation rates per embryo and delivery rates per transfer were measured in recipients. RESULTS Twenty-one (31%) of the donors demonstrated premature luteinization. Serum P was higher on day before hCG, day of hCG, and day after hCG in women demonstrating premature luteinization. However, there were no differences between donor cycles with or without premature luteinization as determined by donor age, ampules of gonadotropins used, day of hCG administration, peak E2, total number of oocytes, and number of mature oocytes retrieved. Ovum recipients were of similar age and had similar E2 exposure (area under the E2 curve) before P administration. Similar fertilization rates, incidence of polyspermia, number of embryos transferred of similar embryo grade, and similar implantation rates and deliveries per transfer were observed in women receiving oocytes from donors with and without premature luteinization, respectively. CONCLUSIONS Similar oocyte quality, fertilization, and polyspermia rates, embryo quality, implantation, and delivery rates suggest that any negative impact of premature luteinization on pregnancy rates in COH cycles from young women is not due to an adverse effect of PL on oocyte and hence embryo quality, but rather on the endometrial environment.

Ovarian hyperstimulation syndrome: A review of pathophysiology

Ovarian hyperstimulation syndrome (OHSS) remains the most serious complication of ovulation induction (OI). In its severest, critical form it is characterized by enormous, cystic ovarian enlargement with massive extravascular fluid shifts and secondary intravascular volume depletion (1,2). This acute fluid shift into third spaces, with accompanying electrolyte imbalance, and hemoconcentration is largely responsible for the serious morbidity (3-6) and occasional mortality (7,8) seen in OHSS. Although the pathophysiology of this syndrome has not been completely elucidated, the underlying mechanism responsible for the clinical manifestation of OHSS appears to be an increase in capillary permeability of mesothelial surfaces (9). Risk factors (10,11)for the OHSS include high serum estradiol (Ez) levels (2,12-14) and multiple immature and intermediate follicles (15-17). Patients with polycystic ovarian disease (PCO) are well-known to be predisposed to this syndrome (18-20). In addition, the OHSS is almost restricted to cycles with either exogenous or endogenous pregnancy-derived, human chorionic gonadotropin (hCG) stimulation (1,2,21,22). The events of OI leading up to the development of the OHSS, for the most part, represent an exaggeration of the normal process of follicular development and ovulation. Thus, a brief and selected review of the normal menstrual cycle is warranted before examining the phenomenon of OHSS.

Immunohistochemical localization of gonadotropin-releasing hormone during implantation in the New Zealand white rabbit

Gonadotropin-releasing hormone was localized immunohistochemically during implantation (gestational days 6 to 14) in the New Zealand White rabbit. During early implantation (days 7 to 9), intense gonadotropin-releasing hormone immunostaining was localized predominantly to the cytoplasm of the nonknob cytotrophoblast with light to moderate staining in the cytoplasm of the syncytiotrophoblast (knob). In later gestation, light to moderate staining of the cytoplasm of the trophoblast at the true placental site was detected. No appreciable change in staining was noted after day 10. Fetal membranes, identified after day 10, showed intense and unchanging immunostaining for gonadotropin-releasing hormone. Obplacental giant cells showed light to moderate nuclear and cytoplasmic gonadotropin-releasing hormone immunostaining. Light to moderate gonadotropin-releasing hormone immunostaining was also noted in the cytoplasm of uterine epithelium and glands. We conclude that immunoreactive gonadotropin-releasing hormone is present in the cytotrophoblast at the time of the earliest embryo-uterine interactions and may play a significant role in implantation and embryo survival.