Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials.

STUDY QUESTION: What is an objective approach that employs measurable and reproducible physiologic changes as the basis for the classification of ovarian hyperstimulation syndrome (OHSS) in order to facilitate more accurate reporting of incidence rates within and across clinical trials? SUMMARY ANSWER: The OHSS flow diagram is an objective approach that will facilitate consistent capture, classification and reporting of OHSS within and across clinical trials. WHAT IS KNOWN ALREADY: OHSS is a potentially life-threatening iatrogenic complication of the early luteal phase and/or early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). The clinical picture of OHSS (the constellation of symptoms associated with each stage of the disease) is highly variable, hampering its appropriate classification in clinical trials. Although some degree of ovarian hyperstimulation is normal after stimulation, the point at which symptoms transition from those anticipated to those of a disease state is nebulous. STUDY DESIGN, SIZE, DURATION: An OHSS working group, comprised of subject matter experts and clinical researchers who have significantly contributed to the field of fertility, was convened in April and November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: The OHSS working group was tasked with reaching a consensus on the definition and the classification of OHSS for reporting in clinical trials. The group engaged in targeted discussion regarding the scientific background of OHSS, the criteria proposed for the definition and the rationale for universal adoption. An agreement was reached after discussion with all members. MAIN RESULTS AND THE ROLE OF CHANCE: One of the following conditions must be met prior to making the diagnosis of OHSS in the context of a clinical trial: (i) the subject has undergone OS (either controlled OS or OI) AND has received a trigger shot for final oocyte maturation (e.g. hCG, GnRH agonist [GnRHa] or kisspeptin) followed by either fresh transfer or segmentation (cryopreservation of embryos) or (ii) the subject has undergone OS or OI AND has a positive pregnancy test. All study patients who develop symptoms of OHSS should undergo a thorough examination. An OHSS flow diagram was designed to be implemented for all subjects with pelvic or abdominal complaints, such as lower abdominal discomfort or distention, nausea, vomiting and diarrhea, and/or for subjects suspected of having OHSS. The diagnosis of OHSS should be based on the flow diagram. LIMITATIONS, REASONS FOR CAUTION: This classification system is primarily intended to address the needs of the clinical investigator undertaking clinical trials in the field of OS and may not be applicable for the use in clinical practice or with OHSS occurring under natural circumstances. WIDER IMPLICATIONS OF THE FINDINGS: The proposed OHSS classification system will enable an accurate estimate of the incidence and severity of OHSS within and across clinical trials performed in women with infertility. STUDY FUNDING/COMPETING INTERESTS: Financial support for the advisory group meetings was provided by Merck & Co., Inc., Kenilworth, NJ, USA. P.H. reports unrestricted research grants from MSD, Merck and Ferring, and honoraria for lectures from MSD, Merck and IBSA. S.M.N. reports that he has received fees and grant support from the following companies (in alphabetic order): Beckman Coulter, Besins, EMD Serono, Ferring Pharmaceuticals, Finox, MSD and Roche Diagnostics over the previous 5 years. P.D., C.C.C., J.L.F., H.M.F., and P.L. report no relationships that present a potential conflict of interest. B.C.T. REPORTS: grants and honorarium from Merck Serono; unrestricted research grants, travel grants and honorarium, and participation in a company-sponsored speaker's bureau from Merck Sharp & Dohme; grants, travel grants, honoraria and advisory board membership from IBSA; travel grants from Ferring; and advisory board membership from Ovascience. L.B.S. reports current employment with Merck & Co, Inc., Kenilworth, NJ, USA, and owns stock in the company. K.G. and B.J.S. report prior employment with Merck & Co., Inc., Kenilworth, NJ, USA, and own stock in the company. All reported that competing interests are outside the submitted work. No other relationships or activities exist that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: Not applicable.

Basal antral follicle number and mean ovarian diameter predict cycle cancellation and ovarian responsiveness in assisted reproductive technology cycles.

OBJECTIVE: To determine the predictive value and define threshold levels for basal antral follicle number and mean ovarian diameter in patients undergoing ART cycles. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS: Two hundred seventy-eight patients who had ovarian measurements performed on cycle day 3 before beginning treatment with gonadotropins. INTERVENTION: Pretreatment ovarian ultrasound measurements. MAIN OUTCOME MEASURE: Number of oocytes retrieved, hormone levels, and cycle outcomes. RESULTS: A direct linear correlation was observed between mean ovarian diameter and basal follicle number. Both measures demonstrated a positive linear correlation with recovered oocytes, basal E(2), and peak E(2). Both demonstrated a negative linear correlation with ampules of gonadotropins administered, days of stimulation, patient age, cycle day 3 FSH, and FSH:LH ratio. An antral follicle count of

Evaluation of basal estradiol levels in assisted reproductive technology cycles.

OBJECTIVE: To determine if basal E(2) screening increases the diagnostic accuracy of basal FSH screening and to determine whether basal E(2) levels correlate with outcome in ART cycles. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENT(S): Two thousand six hundred thirty-four infertility patients. INTERVENTION(S): Cycle outcome was evaluated after grouping patients by basal E(2) levels beginning at <20 pg/mL and extending to >100 pg/mL at 10 pg/mL increments. MAIN OUTCOME MEASURE(S): Retrieved oocytes, pregnancy rate, and cancellation rate. RESULT(S): Cancellation rates were significantly increased in patients with basal E(2) levels of <20 pg/mL or >/=80 pg/mL. Basal E(2) levels neither predicted pregnancy outcome nor correlated with ovarian response in those patients not canceled. CONCLUSION(S): Patients with basal E(2) levels of <20 pg/mL or >/=80 pg/mL had an increased risk for cancellation. Basal E(2) was predictive of stimulation parameters in patients 40 years or older. For those patients who proceeded to retrieval, there were no differences in pregnancy or delivery rates relative to basal E(2) levels. This suggests that irrespective of basal E(2) levels patients who produce more than three maturing follicles in response to stimulation have adequate ovarian reserve as evidenced by their pregnancy rates.

Intracytoplasmic sperm injection increases embryo fragmentation without affecting clinical outcome.

PURPOSE: To examine the effect of intracytoplasmic sperm injection (ICSI) on embryo fragmentation and implantation rates in those embryos chosen for transfer compared to conventional in vitro fertilization (IVF). METHODS: We compared 253 infertility patients (71 ICSI and 182 IVF) with respect to age, semen analysis, number of embryos transferred, embryo fragmentation, implantation rate, and pregnancy rate. Embryo fragmentation was determined by one observer at the same laboratory over the entire study period. RESULTS: A statistically significant difference was observed in mean embryo grade between IVF (2.2 +/- 0.84) and ICSI (2.5 +/- 0.77), P = 0.01. Additionally, the IVF patients had significantly more nonfragmented (grade I) embryos compared to the ICSI group, P < 0.01. CONCLUSIONS: These data suggest that ICSI, irrespective of semen parameters, may increase embryo fragmentation and produce fewer nonfragmented grade I embryos while maintaining implantation and pregnancy rates similar to conventional IVF.

Bilateral transvaginal sacrospinous colpopexy: preliminary experience.

OBJECTIVE: Our goal was to determine how often a transvaginal sacrospinous colpopexy procedure can be done bilaterally. STUDY DESIGN: Between August 1993 and July 1996, 66 patients were prospectively evaluated for uterine prolapse (19 patients) and posthysterectomy vaginal vault prolapse (47 patients). Twenty-six patients (25 with posthysterectomy vaginal vault prolapse) underwent an abdominal sacral colpopexy. The remaining 40 patients (18 with uterine prolapse, 22 with posthysterectomy vaginal vault prolapse) were preoperatively and intraoperatively assessed for a bilateral sacrospinous colpopexy. All patients with uterine prolapse underwent hysterectomy. RESULTS: In 10 of the 18 (56%) patients with uterine prolapse and in 16 of the 22 (73%) patients with posthysterectomy vaginal vault prolapse, bilateral suspension to the sacrospinous ligament was carried out. Follow-up has ranged from 6 to 40 months, and no recurrent vaginal cuff prolapses have been detected in any patients. In 3 patients, however, all in the bilateral fixation categories, distention cystoceles have developed; one patient has undergone a successful anterior colporrhaphy. CONCLUSIONS: The bilateral suspension is different from the unilateral suspension in that the former requires significant intraoperative judgment in its feasibility and in maintaining the width of the vaginal cuff to allow a bilateral suspension without tension. A bilateral fixation appears more attainable in a patient with posthysterectomy vaginal vault prolapse than in one with uterine prolapse.