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Objective: To investigate hospitalizations up to 8 years after live birth among women who used assisted reproductive technology (ART) or who were subfertile compared with women who conceived naturally., Design: Retrospective cohort., Setting: Deliveries among privately insured women aged ≥18 years between 2004 and 2017 from Massachusetts state vital records were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and hospital observational/inpatient stays., Patient(s): We compared patients with ART, medically assisted reproduction (MAR), and unassisted subfertile (USF) delivery with those with fertile delivery., Intervention(s): NA., Main Outcome Measure(s): Postdelivery hospitalization information was derived from the International Classification of Diseases codes for discharges and combined by type. The relative risks and 95% confidence intervals (CIs) of hospitalization for up to the first 8 years postdelivery were modeled., Result(s): Among 492,515 deliveries, 5.6% used ART, 1.6% used MAR, and 1.8% were USF. Compared with fertile deliveries, deliveries that used ART or MAR or were USF were more likely to have hospital utilization (inpatient or observational stay) for any reason for up to 8 years of follow-up (USF, adjusted relative risk [aRR], 1.18 [95% CI, 1.12-1.25]; MAR, aRR, 1.20 [1.13-1.27]; and ART, aRR, 1.29 [1.25-1.34]). Assisted reproductive technology deliveries had an increased risk of hospitalization for conditions of the cardiovascular system (aRR, 1.31 [95% CI, 1.20-1.41]), overweight/obesity (aRR, 1.30 [1.17-1.44]), diabetes (aRR, 1.25 [1.05-1.49]), reproductive tract (aRR, 1.62 [1.47-1.79]), digestive tract (aRR, 1.39 [1.30-1.49]), thyroid (aRR, 2.02 [1.80-2.26]), respiratory system (aRR, 1.13 [1.03-1.24]), and cancer (aRR, 1.40 [1.18-1.65]) up to 8 years after delivery. Deliveries with MAR and subfertility had similar patterns of hospitalization as ART deliveries., Conclusion(s): Women who conceived through fertility treatment or experienced subfertility were at increased risk of subsequent hospitalization resulting from a variety of chronic and acute conditions., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma., Design: Prospective cohort study., Setting: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada)., Patient(s): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization., Intervention(s): None., Main Outcome Measure(s): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count., Result(s): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4)., Conclusion(s): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To compare incidence, risk factors, and etiology of women's deaths in fertile, subfertile, and undergoing assisted reproductive technology (ART) in the years after delivery., Design: Retrospective cohort., Setting: University hospital., Patient(s): Women who had delivered in Massachusetts., Intervention(s): This study used data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System linked to vital records, hospital stays, and the Massachusetts death file. Mortality of patients delivered from 2004-2013 was evaluated through 2015. The exposure groups, determined on the basis of the last delivery, were ART-treated (linked to Society for Assisted Reproductive Technology Clinic Outcome Reporting System), subfertile (no ART but with indicators of subfertility including birth certificate checkbox for fertility treatment, prior hospitalization for infertility [International Classification of Disease codes 9 628 or V23], and/or prior delivery with checkbox or ART), or fertile (neither ART nor subfertile). Numbers (per 100,000 women-years) and causes of death were obtained from the Massachusetts death file., Main Outcome Measure(s): Mortality of women after delivery in each of the three fertility groups and the most common etiology of death in each., Result(s): We included 483,547 women: 16,429 ART, 11,696 subfertile, and 455,422 fertile among whom there were 1,280 deaths with 21.1, 25.5, and 44.7 deaths, respectively, per 100,000 women-years. External causes (violence, accidents, and poisonings) were the most common reasons for death in the fertile group. Deaths occurred on average 46 months after delivery. When external causes of death were removed, there were 19.1, 17.0, and 25.6 deaths per 100,000 women-years and leading causes of death in all groups were cancer and circulatory problems., Conclusion(s): The study presents reassuring data that death rates within 5 years of delivery in ART-treated and subfertile women do not differ from those in fertile women., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare neonatal health outcomes after fresh versus frozen ET (FET)., Design: Retrospective analysis of a population-based database of linked clinically assisted reproductive technology (ART) data with state vital records. Multivariable logistic regression was used to model the association between deliveries from fresh versus FET and adverse health outcomes, controlling for maternal characteristics., Setting: Not applicable., Patient(s): Live-born singleton infants born to Massachusetts women who conceived by fresh or FET after ART using autologous oocytes between July 1, 2004, and December 31, 2013., Intervention(s): None., Main Outcome Measure(s): Preterm birth, low birth weight, neonatal mortality, birth defects, organ system conditions., Result(s): Compared with infants conceived from fresh embryos, those born to mothers who underwent FET were less likely to be small for gestational age (adjusted odds ratio [AOR] = 0.56; 95% confidence interval [CI], 0.44-0.70) and low birth weight (AOR = 0.72; 95% CI, 0.59-0.88) but more likely to be large for gestational age (AOR = 1.47; 95% CI, 1.26-1.70) and to experience greater odds of infectious disease (AOR = 1.46; 95% CI, 1.03-2.06), respiratory (AOR = 1.23; 95% CI, 1.07-1.41), and neurologic (AOR = 1.32; 95% CI, 1.04-1.68) conditions. There were no statistically significant differences in preterm birth, neonatal mortality, birth defects, cardiovascular, hematologic, and gastrointestinal/feeding conditions, and for infants ≥ 35 weeks, no statistically significant differences in prolonged hospital stay (>3 days for vaginal delivery, >5 days for cesarean)., Conclusion(s): Compared with infants conceived from fresh ET, those born by FET have higher birth weight but increased odds of infectious disease, hematologic, respiratory, and neurologic abnormalities. These risks should be considered when making decisions on fresh versus FET., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of frozen, compared with fresh, embryo transfer on neonatal and pediatric weight and weight gain trajectory., Design: Retrospective cohort study., Setting: Academic medical center., Patient(s): Women who underwent fresh or frozen embryo transfer at the Mayo Clinic from 2010 to 2014. All included embryo transfers resulted in a singleton live birth. Children were followed from birth to at least 18 months. When possible, growth was evaluated to 5 years of age., Interventions(s): Fresh versus frozen embryo transfer., Main Outcome Measure(s): Propensity score methodology was used to balance the two groups by maternal characteristics and gestational age before evaluating outcomes. Each infant and childhood growth measurement was compared between the two groups., Result(s): Of the 136 women, 87 underwent a fresh embryo transfer and 49 underwent a frozen embryo transfer. Birth length and head circumference were significantly different in infants delivered after fresh versus frozen embryo transfer. There was a statistically significant difference in birth weight between infants born after fresh versus frozen embryo transfer. However, this difference did not persist when adjusted for gestational age, sex, and maternal factors. Childhood growth measurements including age- and sex-specific weight, and body mass index percentiles were not significantly different between groups., Conclusion(s): This study confirmed an association of frozen embryo transfer and increased birth weight, but the association did not persist when controlling for confounding maternal factors. We found no effect of fresh versus frozen embryo transfer on neonatal weight and childhood weight gain trajectory., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To quantify the effect of medical and obstetrical factors on the odds of cesarean delivery, comparing assisted reproductive technology (ART)-treated women and women with subfertility not treated with ART versus fertile women., Design: Retrospective cohort., Setting: Not applicable., Patient(s): Singleton deliveries to primiparous women; with the source of this data being the Massachusetts vital and hospital records linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System data (2004-2010)., Intervention(s): None., Main Outcome Measure(s): Mode of delivery., Result(s): The 173,130 deliveries included 5,768 ART-treated, 2,657 subfertile (1,627 non-ART medically assisted reproduction [MAR] and 1,030 unassisted infertile), and 164,705 fertile pregnancies and 117,743 vaginal and 55,387 cesarean deliveries. ART-treated women were older, more often white and non-Hispanic, and with more private insurance, previous uterine surgery, gestational diabetes, pregnancy hypertension, bleeding, and placental complications than fertile women. Overall rates of cesarean delivery were 45.7%, 43.3%, and 31.1% for ART-treated, subfertile, and fertile women and 41.7% and 45.9% for MAR and unassisted infertile deliveries. When adjusted for demographics, underlying medical factors, previous uterine surgery, and placental and delivery complications, adjusted odds ratios (ORs) compared with fertile women were 1.27 for ART-treated and 1.15 for subfertile women, with greater odds among unassisted infertile (OR 1.26) but not MAR (OR 1.09) women. The strongest confounders of odds of cesarean delivery were age and previous uterine surgery., Conclusion(s): ART and unassisted infertility were associated with greater odds of cesarean compared with fertile women. Underlying medical and obstetrical risks had strong confounding effects strongly attenuating the odds for cesarean delivery., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate a new fully automated antimüllerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved., Design: Prospective cohort study., Setting: Thirteen private and academic fertility centers in the United States., Patients(s): A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC)., Intervention(s): None., Main Outcome Measure(s): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15., Result(s): The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%., Conclusion(s): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The Society for Assisted Reproductive Technology (SART) was established within a few years of assisted reproductive technology (ART) in the United States, and has not only reported on the evolution of infertility care, but also guided it toward improved success and safety. Moving beyond its initial role as a registry, SART has expanded its role to include quality assurance, data validation, practice and advertising guidelines, research, patient education and advocacy, and membership support. The success of ART in this country has greatly benefited from SART's role, as highlighted by a series of graphs. SART continues to set the standard and lead the way., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To develop a model predictive of live-birth rates (LBR) and multiple birth rates (MBR) for an individual considering assisted reproduction technology (ART) using linked cycles from Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) for 2004-2011., Design: Longitudinal cohort., Setting: Clinic-based data., Patient(s): 288,161 women with an initial autologous cycle, of whom 89,855 did not become pregnant and had a second autologous cycle and 39,334 did not become pregnant in the first and second cycles and had a third autologous cycle, with an additional 33,598 women who had a cycle using donor oocytes (first donor cycle)., Intervention(s): None., Main Outcome Measure(s): LBRs and MBRs modeled by woman's age, body mass index, gravidity, prior full-term births, infertility diagnoses by oocyte source, fresh embryos transferred, and cycle, using backward-stepping logistic regression with results presented as adjusted odds ratios (AORs) and 95% confidence intervals., Result(s): The LBRs increased in all models with prior full-term births, number of embryos transferred; in autologous cycles also with gravidity, diagnoses of male factor, and ovulation disorders; and in donor cycles also with the diagnosis of diminished ovarian reserve. The MBR increased in all models with number of embryos transferred and in donor cycles also with prior full-term births. For both autologous and donor cycles, transferring two versus one embryo greatly increased the probability of a multiple birth (AOR 27.25 and 38.90, respectively)., Conclusion(s): This validated predictive model will be implemented on the Society for Assisted Reproductive Technology Web site (www.sart.org) so that patients considering initiating a course of ART can input their data on the Web site to generate their expected outcomes., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the effect of unilateral oophorectomy (UO) by assessing ovarian reserve (OVR) and the response to gonadotropin stimulation in women with UO undergoing in vitro fertilization (IVF) compared with the response of the ipsilateral ovary of women without UO., Design: Historical cohort study., Setting: Academic fertility clinic., Patient(s): Fifty-one women with single ovary compared with a referent group with both ovaries in a 1:2 fashion., Intervention(s): None., Main Outcome Measure(s): Day-3 follicle-stimulating hormone (FSH), estradiol, and antral follicle counts as measures of OVR, and IVF outcomes including number of follicles aspirated and oocytes retrieved., Result(s): The baseline demographics and serum markers of OVR were not different. Referent women had greater follicular yield and oocyte numbers when compared with women with UO; however, when compared with the ipsilateral ovary of the referents, women with UO had a higher antral follicle count and greater follicle and oocyte numbers. In multivariate analyses, the ovary from women with UO was more likely to yield more than the median number of follicles and oocytes than the ipsilateral ovary in referent women. Live-birth rates in both groups were similar., Conclusion(s): Our results suggest that the remaining ovary appears to compensate in follicular yield after UO in women, confirming the animal data. Women with UO can be reassured and appropriately counseled regarding IVF., (Published by Elsevier Inc.)

Objective: To determine whether there is a correlation between preovulatory endometrial stripe thickness (EST) and pregnancy rates in clomiphene citrate (CC)/IUI cycles., Design: Retrospective cohort., Setting: Infertility clinic of an academic medical center., Patient(s): A total of 262 patients completed 562 transvaginal ultrasound-monitored CC/IUI cycles from January 2005 through December 2012., Intervention(s): All patients received oral CC. In 362 of the cycles, a single dose of gonadotropin was administered on cycle day 9 (MinStim). A transvaginal ultrasound was performed on cycle day 10, 11, or 12., Main Outcome Measure(s): Pregnancy rate per initiated cycle., Result(s): A total of 91 pregnancies ensued, yielding a pregnancy rate of 16.2% per initiated cycle. Pregnancy rates did not vary with EST <6 mm, 6-9 mm, and >9 mm (14.8%, 16.3%, and 19.0%, respectively). There was no significant difference in mean EST between stimulation types (6.8 mm for CC vs. 6.7 mm for MinStim). When conception and nonconception cycles were compared, no difference in mean EST (6.9 mm vs. 6.8 mm, respectively) was observed. Area under the receiver operating characteristic curve for the probability of pregnancy based on EST was 0.51., Conclusion(s): Preovulatory EST had no significant correlation with pregnancy rates in CC/IUI cycles. The decision to switch from CC to another treatment strategy should be influenced by factors other than thin endometrial stripe., (Published by Elsevier Inc.)

Objective: To assess the influence of infertility and fertility drugs on risk of ovarian tumors., Design: Case-control study (Mayo Clinic Ovarian Cancer Study)., Setting: Ongoing academic study of ovarian cancer., Patient(s): A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use., Intervention(s): None., Main Outcome Measure(s): Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders., Result(s): Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors., Conclusion(s): We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation., (Published by Elsevier Inc.)

Objective: To assess sperm morphology with Tygerberg (strict) and World Health Organization (WHO) 3rd criteria for intrauterine inseminations (IUI) between two eras to determine if there was a difference in pregnancy rates., Design: Retrospective study., Setting: Academic institution., Patient(s): 127 couples with 290 IUI treatments during 1996-97 (era 1) and 133 couples with 317 IUI treatments during 2005-06 (era 2)., Intervention(s): None., Main Outcome Measure(s): Pregnancy rates per cycle and couple., Result(s): Average sperm morphology was higher in era 1 than era 2 for both WHO 3rd (37 ± 13% vs. 23 ± 10%) and strict criteria (8.0 ± 5.0% vs. 4.0 ± 3.0%). Pregnancy rates per cycle were 5.9% versus 19.8% in era 1 and 16.7% versus 19.3% in era 2 for couples with WHO 3rd morphology <30% or ≥30%, respectively. Pregnancy rates per cycle were 2.7% versus 15.0% in era 1 and 13.3% versus 14.7% in era 2 for couples with strict morphology ≤4% or >4%, respectively., Conclusion(s): There was a strong relationship between morphology and IUI outcome in era 1 that was not present in era 2. These results suggest that classification drift increased the percentage of men diagnosed with teratozoospermia and resulted in a loss of predictive value., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This case-control study shows a strong association between migraine history and development of ovarian hyperstimulation syndrome (OHSS). We hypothesize there may be a similar gene variant that predisposes women to both migraines and OHSS and identification will lead to optimal therapy, not only for OHSS, but also for women who suffer from migraines., (Published by Elsevier Inc.)

Objective: To evaluate factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome., Design: Historic cohort study., Setting: Clinic-based data., Patient(s): The population included 214,219 ART cycles performed during 2004 to 2006 and reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System Online database. The study population was limited to cycles of autologous, fresh embryo transfers to women without any treatment complications (212,041), and those developing moderate (1,523) or severe (655) OHSS., Intervention(s): None., Main Outcome Measure(s): Risk factors for developing OHSS, and its effect on achieving a pregnancy and live birth, as adjusted odds ratios., Result(s): Compared with white women, the risk of developing OHSS was increased for Black women (any OHSS, 1.88; severe OHSS, 2.93) and decreased for Hispanic women (any OHSS, 0.79). Ovarian hyperstimulation syndrome was associated with ovulation disorders (2.01), tubal factors (1.24), and unexplained factors (1.36). Ovarian hyperstimulation syndrome increased the odds of achieving a pregnancy (1.98 with any OHSS, 2.68 with severe), a live birth (any OHSS, 1.86), and a multiple live birth (1.58 with any OHSS, 1.86 with severe). The presence of any OHSS increased the risk of an adverse pregnancy outcome (stillbirth, low birthweight, or preterm birth) by 26% and low birthweight among singletons by 40%., Conclusion(s): Ovarian hyperstimulation syndrome is associated with a higher likelihood of pregnancy, and multiple gestations, but also greater risks for adverse pregnancy outcomes., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To elucidate the clinical profile of adenomyosis by comparison with uterine leiomyomas., Design: Retrospective case-control study., Setting: Academic medical center., Patient(s): The study comprised 76 women undergoing hysterectomy with adenomyosis and 152 women with uterine leiomyomas but no adenomyosis., Intervention(s): Retrospective medical record review of hospital and ambulatory records., Main Outcome Measure(s): Comparison of women undergoing hysterectomy with a sole pathologic finding of adenomyosis and women with leiomyomas alone., Result(s): Adenomyosis was independently associated with younger age (41.1 years vs. 44.3 years), history of depression (57.1% vs. 24.7%), dysmenorrhea (65.7% vs. 42.3%), and pelvic pain (52.9% vs. 21.1%) in a multivariable unconditional logistic regression analysis compared with women with leiomyomas, where women from both groups had gynecologic symptoms. Furthermore, in a second multivariate model where all subjects had uteri weighing>150 g, women with adenomyosis were more likely to have a history of depression (52.6% vs. 22.2%) and endometriosis (26.3% vs. 2.8%) compared with women with leiomyomas., Conclusion(s): Women undergoing hysterectomy with a histologic diagnosis of adenomyosis have a distinct symptomatology and medical history compared with women with leiomyomas. Better understanding of this disease is required to improve diagnosis and management., (Copyright (c) 2010. Published by Elsevier Inc.)

Objective: To investigate the strategies used to decrease the risk of ovarian hyperstimulation syndrome (OHSS) and their impact on pregnancy and live birth rates., Design: Retrospective cohort analysis., Setting: University hospital., Patient(s): One hundred eighty-eight patients undergoing fresh in vitro fertilization (IVF) cycles between 2000 and 2004, with peak serum estradiol levels >2500 pg/mL and presumed to be at risk for OHSS., Intervention(s): Coasting and elective embryo cryopreservation were evaluated for their effect on OHSS and live birth rates., Main Outcome Measure(s): Pregnancy, live birth rates, and OHSS incidence., Result(s): Out of 188 patients at risk for OHSS, 21 patients had their cycles coasted (group 1), and elective embryo cryopreservation was performed in 32 patients (group 2). In 135 patients with no other risk factors, ovulation was triggered with human chorionic gonadotropin and embryo transfer was performed (group 3). The incidence in our IVF population was 38 out of 1002 (3.8%). The overall incidence of OHSS for those who had an estradiol level >2500 pg/mL was 20.2% (38 out of 188), and none of the patients in group 1 developed OHSS; 13 out of 32 patients in group 2 (40.6%) and 25 out of 135 (18.5%) patients in group 3 developed OHSS. The live birth rate was 38%, 40%, and 45% in groups 1, 2, and 3, respectively, and the cumulative live birth rate was 52%, 75%, and 59%, respectively., Conclusion(s): Elective cryopreservation of embryos with subsequent frozen embryo transfer and coasting are effective ways of maximizing pregnancy and limiting severe OHSS., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Controlled-rate frozen and vitrified mature human oocytes were thawed or warmed and parthenogenically activated using ionomycin and 6-dimethylaminopurine to assess pronuclear development compared with fresh controls. This chemical activation model provides a useful tool for laboratories to assess proficiency before offering oocyte cryopreservation to their patients.

Objective: To describe an outpatient treatment protocol for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms with minimal side effects., Design: Case series., Setting: Midwestern academic reproductive endocrinology division., Patient(s): Four consecutive patients, diagnosed with OHSS, who presented after oocyte retrieval but before embryo transfer., Intervention(s): All embryos were frozen and each patient was treated with the same dopamine agonist and GnRH antagonist protocol., Main Outcome Measure(s): Daily weights, days to resolution of clinical symptoms, side effects of the treatment protocol, and whether or not acute care or hospitalization was necessary., Result(s): The most rapid weight loss was within the first 5 days of treatment. The average time to resolution of clinical symptoms was 5.75 days. No side effects were reported and no patients required acute care or hospitalization., Conclusion(s): Dopamine agonists and GnRH antagonists, when given together at the time of diagnosis of OHSS, appear to work rapidly and effectively to diminish the clinical symptoms of the disease. The potential benefit of finding an outpatient treatment for OHSS with rapid onset and minimal side effects warrants further investigation into this protocol.

Objective: To determine if 3 months of preoperative gonadotropin-releasing hormone agonist (GnRH-a) treatment decreases postoperative uterine adhesions after open abdominal surgery for the removal of uterine fibroids., Design: Prospective, randomized, clinical study., Setting: A tertiary care medical center., Patient(s): Women of reproductive age with symptomatic uterine fibroids not amenable to hysteroscopic removal., Intervention(s): Twenty patients underwent an initial abdominal myomectomy followed by a second-look laparoscopy for evaluating uterine adhesions after random allocation to groups receiving either GnRH analog or placebo for 3 months before the initial surgery., Main Outcome Measure(s): Adhesion formation between treatment groups and by incision number and aggregate length., Result(s): Presurgical GnRH-a treatment did not decrease adhesion formation compared with placebo. For every additional centimeter of incision length, the total adhesion area over the uterine serosal surface increased by 0.55 cm(2). The number of myomas removed and the number of incisions were positively correlated with total adhesion area., Conclusion(s): Preoperative treatment with GnRH-a for 3 months before open abdominal myomectomy did not decrease postoperative uterine adhesions. Following the standards of good surgical technique, adhesions are minimized with fewer and smaller incisions.

Objective: To describe a unique case of recurrent aneuploidy and the use of preimplantation genetic screening (PGS)., Design: Case report., Setting: Midwest academic medical center., Patient(s): A 36-year-old woman with two trisomy 21 offspring., Intervention(s): Preimplantation genetic screening., Main Outcome Measure(s): Karyotype of embryos, liveborn eukaryotic infant., Result(s): Preimplantation genetic screening was performed on three cryopreserved embryos, followed by a two-embryo transfer yielding a eukaryotic infant., Conclusion(s): Preimplantation genetic screening may prove to be useful as a diagnostic tool to help ensure a euploid pregnancy when termination is not a viable option for a couple.

Young physicians in our current environment integrate large amounts of information, tactile skill, and constant practice to become superb practitioners. To help them attain their goal, good mentors with qualities of openness, humility, commitment, patience, receptive listening, and confidentiality can help them efficiently guide their careers toward chosen goals.

Objective: To determine the role of saline infusion sonography (SIS) in uterine evaluation before a frozen embryo transfer (FET) cycle., Design: Retrospective cohort analysis., Setting: University hospital., Patient(s): Thirty-six patients who had uterine evaluation by SIS before FET cycle., Intervention(s): The SIS was performed in the follicular phase of the menstrual cycle before the actual FET cycle., Main Outcome Measure(s): The SIS findings, clinical pregnancy rate (PR), ongoing PR, and correlation between positive SIS findings with and without subsequent treatment and pregnancy outcome., Result(s): Positive SIS findings were found in 11/36 patients (30.5%), which included uterine septum (9.0%), endometrial polyp (45.4%), intramural fibroid with normal cavity (9.0%), cystic endometrial changes (9.0%), cervical stenosis (18.1%), and calcification with normal cavity (9.0%). The overall clinical PR in all groups was 51.4%, with an ongoing PR of 45.7%. Patients with positive SIS finding who underwent subsequent hysteroscopic correction (7/11) had a clinical PR of 85.7% as compared to 54.1% in patients with normal uterine cavity (24/35). Patients with positive SIS findings and no operative hysteroscopy (4/11) had a clinical PR of 50% and pregnancy loss rate of 100%., Conclusion(s): Obtaining an SIS before the FET cycle can be helpful in the detection of uterine abnormalities. If time since uterine evaluation has been more than 1-2 years, performing an SIS is recommended as subsequent correction of the anomalies may improve FET outcome.

Clinicians have studied the effectiveness of their IVF practice with a presumed goal of process improvement. The use of standardized patients to compare IVF outcomes is questioned.

Objective: To compare the diagnostic accuracy, pain scores, and procedure length of outpatient hysteroscopy (OHS), hysterosalpingography (HSG), and saline infusion hysterosonography (SIS) for evaluation of the uterine cavity of infertile women., Design: Prospective, randomized, investigator-blind study., Setting: Tertiary infertility clinic., Patient(s): Forty-six consecutive infertile women., Intervention(s): Outpatient HSG, OHS, and SIS, followed by operative hysteroscopy (HS)., Main Outcome Measure(s): Uterine abnormalities, procedure length, and subjective pain., Result(s): Fifty-nine percent of infertile subjects were found to have an abnormality on at least one of three outpatient uterine evaluations. When compared with the case of definitive operative HS, 60% of abnormalities were correctly classified by HSG, 72% by OHS, and 52% by SIS (P: NS). When comparing all combinations of 2 outpatient screening tests to operative hysteroscopy, 68% were correctly classified by HSG/OHS, 58% by HSG/SIS, and 64% by OHS/SIS (P: NS). The average time length for the OHS was 9.1 min., which was significantly greater than for both HSG (average, 5.3 min) and SIS (average, 6.1 min.) (P<.0001 for both). HSG and SIS were not statistically different regarding procedure time length. The average pain score (0-10) for SIS was 2.7, compared with 5.8 and 5.3 for HSG and OHS, respectively. Both HSG and OHS mean pain scores were significantly greater than the SIS mean., Conclusion(s): OHS, SIS, and HSG were statistically equivalent regarding evaluation of uterine cavity pathology in infertile women.

Objective: To determine the cost-effectiveness, safety, and success of microsurgical tubal anastomoses performed by minilaparotomy as an outpatient., Design: Retrospective., Setting: Military tertiary care medical center., Patient(s): Seventy consecutively seen women of reproductive age who were undergoing surgical reversal of sterilization from August 1, 1993, through August 1, 1995., Intervention(s): Microsurgical sterilization reversal by minilaparotomy was performed as an inpatient (group 1, 47 patients) or as an outpatient (group 2, 23 patients)., Main Outcome Measure(s): Cost, complication rate, pregnancy rate., Result(s): The procedure cost more for inpatients ($3,116) than for outpatients (!,456). Pregnancy rates were similar (56% in group 1 vs. 75% in group 2). There was only one complication in the series., Conclusion(s): Outpatient microsurgical sterilization reversal performed by minilaparotomy is as safe and effective as the inpatient procedure and is less expensive.

Objective: To investigate the diagnostic accuracy of microlaparoscopy in comparison to laparoscopy with a standard 10-mm laparoscope., Design: Prospective evaluation by two independent observers., Setting: Academic Medical Center., Patient(s): Ten patients scheduled to undergo diagnostic laparoscopy for the indications of infertility and/or chronic pelvic pain., Intervention(s): Two surgeons were present for each operation. Diagnostic laparoscopy was performed using the Microlap 2-mm laparoscope (Imagyn Medical Inc., Lagun Niguel, CA). Standard diagnostic laparoscopy was then performed using a 10-mm laparoscope. After each procedure, each surgeon reported his or her observations in a confidential manner to a third person to record., Main Outcome Measure(s): Endometriosis and adnexal adhesions were staged. Observations made with the microlaparoscope were compared with those obtained with a standard 10-mm laparoscope for each surgeon. The observations of both surgeons were also compared with each other's to evaluate interobserver differences., Result(s): Operative findings reported by each individual surgeon using the microlaparoscope correlated with the operative findings reported using the larger laparoscope. Scores for both endometriosis and adnexal adhesions did not differ in any significant way. Endometriosis scores differed by no more than 6 points, and adhesion scores differed by no more than 2 points, with no subsequent change in severity classification for either finding. Furthermore, when comparing the additional operative findings of the two surgeons, no difference was noted when using either the microlaparoscope or a standard 10-mm laparoscope., Conclusion(s): The diagnostic accuracy achieved with microlaparoscopy is comparable to that achieved with standard 10-mm laparoscopy.

Objective: To identify factors influencing the development of endometrial autografts in a monkey model of endometriosis., Design: Prospective, comparative study., Setting: Animal research unit., Subjects: Thirty regularly cycling cynomolgus monkeys in three groups of 10 each., Interventions: Endometrium was minced and spilled into the cul-de-sac in group 1. In group 2, the tissue additionally was digested enzymatically. In group 3, the tissue was incubated with a protease inhibitor., Main Outcome Measures: Staging laparotomies after 3 weeks and 3 months., Results: In groups 1, 2, and 3, moderate or severe disease was seen in eight, two, and four monkeys, respectively, after 3 weeks and in eight, three, and two monkeys, respectively, at 3 months., Conclusions: An intact structure leads to ectopic implantation of endometrial fragments in most cases. Conversely, enzymatic digestion of endometrial fragments and treatment with proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that influence extracellular matrix remodeling may play a role in the pathogenesis of human endometriosis.

Objective: To determine the contribution of estrogen in the development of pelvic adhesions during myometrial surgery., Design: A randomized, prospective study in the nonhuman primate., Setting: A primate colony, Department of Obstetrics and Gynecology, Eastern Virginia Medical School., Interventions: All primates were assigned prospectively to one of three treatment groups: [1] GnRH analogue (GnRH-a), [2] mifepristone, or [3] vehicle control. After 3 months of treatment, a standard uterine fundal hysterotomy, for full thickness endometrial biopsy, was performed at the time of exploratory laparotomy, with subsequent scoring of utero-omental adhesions to the hysterotomy site at a future staging procedure based upon adhesion area, vascularity, and tenacity. Serum was drawn on the day of surgery for E2 determination. Endometrial height, from the surface interface between the endometrium and myometrium, was used as a bioassay of estrogen activity., Results: The hypoestrogenic (GnRH-a) group and the mifepristone group had significantly fewer utero-omental adhesions compared with the normally cycling control monkeys as measured by a lower adhesion score. Similarly, the endometrial thickness was significantly reduced in the GnRH-a and mifepristone groups (one-third) compared with the cycling controls, demonstrating the effects of either hypoestrogenism or noncompetitive estrogen antagonism. Serum E2 on the day of surgery was predictive of the postoperative adhesion score by both a regression analysis and analysis of covariance., Conclusions: The actions of E2 seem to have a dramatic effect on the formation of pelvic adhesions after myometrial surgery.

Objective: To examine whether placental protein 14 (PP14) may affect directly those sperm functions crucial to fertilization and early embryo development., Design: In these prospective studies, we evaluated semen samples of fertile men incubated under capacitating conditions with and without PP14., Setting: Academic tertiary institution., Interventions: Biologically active PP14 was purified from human midtrimester amniotic fluid by anion exchange and immunoaffinity chromatography. After separation of the motile fraction, spermatozoa were incubated for 30 minutes with or without PP14 (concentration range of 0.01 to 100 micrograms/mL), washed, and then aliquots were prepared for use in the different assays. Human sperm-zona pellucida (ZP) binding was assessed using the hemizona assay (HZA) in a 4-hour gametes coincubation period. Sperm motility parameters were evaluated using a computerized semen analyzer. The acrosome reaction (AR) was determined by fluorescein isothiocyanate-conjugated Pisum sativum agglutinin and indirect immunofluorescence., Main Outcome Measures: Sperm-ZP binding, sperm motility patterns, and AR., Results: Preincubation of sperm (and not the hemizonae) with PP14 produced a significant and dose-dependent inhibition of binding in the HZA. Monoclonal antibodies generated against PP14 showed no direct effect in the HZA and partially neutralized the inhibitory activity of PP14 in the HZA. Insulin-like growth factor binding protein-1 (IGFBP-1), an endometrial stromal cell product, showed no effect in the HZA. Neither PP14 nor IGFBP-1 interfered with sperm motility parameters or the AR., Conclusions: Placental protein 14 produced a potent, fast, and dose-dependent inhibition of binding of human spermatozoa to the human ZP without affecting other prefertilization events (i.e., hyperactivated motility or AR). The detrimental effect on sperm-zona interaction seems to be specific for this endometrial epithelial protein (not observed with an endometrial stromal product) and may have fundamental bearance to the fertilization process thus providing a mechanism for endometriosis-related infertility.

Objectives: To determine the effectiveness of two different surgical membranes in preventing postoperative adhesions as compared with control and to evaluate the benefit as compared with "second-look" adhesiolysis., Design: A randomized, prospective, crossover study., Setting: A colony of individually caged non-human primates, Department of Obstetrics and Gynecology, Eastern Virginia Medical School Norfolk, Virginia., Interventions: Hysterotomy or adhesiolysis at the time of exploratory laparotomy, with subsequent scoring of adhesions based on area, vascularity, tenacity, and adhesion score., Results: The combined crossover data reveal that both surgical barriers are superior in adhesion prevention to microsurgical technique alone. Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane; WL Gore and Associates, Flagstaff, AZ) was better than oxidized regenerated cellulose (Interceed; Johnson and Johnson Medical, Inc., Arlington, TX) with respect to adhesion area, tenacity, and vascularity, with a significant improvement in the total adhesion score. Second-look adhesiolysis resulted in significant adhesion reduction in the control group, making second-look adhesiolysis statistically similar to the use of either barrier alone (without subsequent adhesiolysis). Gore-Tex removal does not result in adhesion formation as determined by third-look surgery., Conclusions: Both Interceed and Gore-Tex show a reduction in the prevention of postsurgical adhesions after hysterotomy incisions, as compared with microsurgical technique alone. Second-look adhesiolysis is as effective as either barrier in the reduction of permanent pelvic adhesions.

Eight infertility patients with proximal tubal occlusion by HSG and at least one other independent method underwent falloposcopy to evaluate the etiology of uterotubal occlusion. Patency was established in 9 of 12 tubes evaluated. Falloposcopy revealed 5 tubes with multiple or extensive intratubal lesions that would be unsuitable for unilocular tubal resection with subsequent reanastomosis. In addition, 5 tubes were visually normal or had only minor pathological changes (2 of these patients became pregnant). Only 2 of the tubes examined in a single patient would be considered candidates for microsurgical correction at laparotomy. Falloposcopy will become a useful adjunct in the evaluation of the patient with suspected tubal infertility. It provides information regarding the condition of the tubal mucosa that is unavailable by any other technique, adding precision to surgical techniques when they are deemed necessary while directing other patients to assisted reproductive technologies. However, falloposcopy is still in its infancy and data from larger studies are needed.

Objective: To study autoimmune aspects of endometriosis., Design: Lymphoblast transformation and hemolytic plaque formation were used to assess specific T- and B-cell activity against endometrial antigens., Setting: Military teaching hospital., Patients: Ninety-four healthy women of reproductive age undergoing diagnostic laparoscopy as part of an evaluation for infertility or chronic pelvalgia were accordingly grouped into those with normal pelvic peritoneum (20), mild endometriosis (50), and severe endometriosis (24)., Main Outcome Measure: The study assessed the proliferative and humoral responses of lymphocytes from women with and without endometriosis to endometrial antigens and quantified the number of B-cell precursors, T-helper cells, and T-suppressor cells to these antigens., Results: Unfractionated endometrial antigens were similarly blastogenic for lymphocytes from women with and without endometriosis. Despite equivalent numbers of B-cell precursors to these antigens, antiendometrial antibody responsiveness appears to have increased in women with mild endometriosis because of a decrease in T-suppressor cell activity and declined in women with severe endometriosis because of a further drop in T-suppressor cell activity and an increase in T-helper cell activity, as compared with women without endometriosis., Conclusions: Taken together, these experiments support the possibility that pelvic endometriosis may result from a break in specific T-cell tolerance rather than nonspecific polyclonal activation of responder lymphocytes.

Objective: To evaluate the effect of peritoneal fluid (PF) from patients with endometriosis on gamete interaction under hemizona assay (HZA) conditions., Design: The HZA was used to study the effect of PF from patients with endometriosis on sperm binding to the zona pellucida using media and normal PF as controls., Setting: The patients were collected from a university hospital infertility clinic., Patients: Peritoneal fluid from 16 women being evaluated for infertility or sterilization who were found to have endometriosis at surgery was used. Three normal patients, who were being sterilized, had PF that was used as a control., Results: Results suggest that there is a significant reduction in the number of tightly bound sperm to the zona surface in endometriosis specimens as reflected in the hemizona index and that this effect is directly related to the stage of the disease., Conclusions: Although the sample is small, this methodology may help to elucidate one of the mechanisms responsible for endometriosis-associated infertility.

Objective: To achieve a better understanding of the variability in sperm and oocyte binding capacities will optimize use of the hemizona assay (HZA) as a predictor of sperm function., Design: Limitations of the HZA were more clearly delineated by current studies: (1) variability of sperm binding capacity of men over a 90-day interval; (2) variability of sperm binding using different oocytes; and (3) lower limits of the number of sperm bound from the fertile control in two laboratories., Patients: Semen was obtained from proven fertile men and one subfertile individual., Main Outcome Measure: The number of sperm tightly bound to the hemizona were measured and compared., Results: In the initial study, 6 fertile control men exhibited a similar degree of variability in zona binding when studied over a 90-day interval. Average sperm binding for individuals ranged from 68 to 127. Second, 3 of the 15 simultaneous assays showed very low numbers of sperm bound, indicating that 20% of the zonae had poor binding. Third, from 18 men who had 0% fertilization in an in vitro fertilization system using mature oocytes, evaluation of their sperm by HZA was performed. The sperm bound poorly and the 95% confidence interval was 20 sperm bound. Thus, the fertile controls should bind greater than 20 sperm to distinguish them from the infertile group in the HZA system resulting in a valid assay., Conclusions: With these guidelines, applications of the HZA may be made with greater reassurance of a valid bioassay of sperm fertilizing potential.

A monoclonal antibody, T-6, useful for detecting acrosome-reacted sperm based on an immunofluorescent assay, was employed to evaluate acrosomal status of human sperm that were tightly bound to hemisected human zonae pellucidae (hemizona assay). Over 90% of the bound sperm evaluated exhibited immunofluorescent patterns indicative of acrosome reaction. This staining method for evaluating the acrosomal status of sperm bound to the zona pellucida may enable definition of a group of male infertility patients heretofore not recognized.

This study aimed: (1) to evaluate the zona-binding capacity of patients with abnormal sperm morphology, using standard hemizona assay (HZA) conditions and increasing sperm insemination concentration during the assay and (2) to determine the insemination concentration needed to obtain equality in the number of tightly bound sperm to matching hemizonae, using sperm from teratozoospermic patients versus proven fertile controls. The minimum concentration of motile sperm from fertile controls necessary to validate HZA results was 250,000/mL (35.4 +/- 5.6 tightly bound sperm; mean +/- SE). The "effective number of sperm" (morphologically normal with high motility) was 60,750/mL. Each teratozoospermic patient had a unique, (higher) sperm insemination concentration (range: 0.5 X 10(6) to 2.0 X 10(6) motile sperm/mL) necessary to equal the number of tightly bound sperm representing the lower 95% confidence interval for the control sample (at 0.5 X 10(6) motile sperm/mL) with the matching hemizona. These results suggest that the HZA may be used as an indicator of the sperm insemination concentration during in vitro fertilization in patients with teratozoospermia.

The authors employed a gonadotropin-releasing hormone agonist (GnRH-a) (D-His6-pro9-NET-GnRH) to treat 19 patients with symptomatic uterine leiomyomata, by daily subcutaneous injections (4 micrograms/kg) for 6 months. After therapy, patients were followed for 6 months without any therapy. Uterine volumes were measured by serial pelvic examinations and pelvic sonography. Measurements of serum estradiol, luteinizing hormone, and follicle-stimulating hormone were used to assess treatment response. Pituitary desensitization and hypoestrogenemia were achieved in all within 8 weeks, and in 18 of 19, hypoestrogenemia was maintained for the duration. Uterine volume at the conclusion of therapy (207.5 +/- 152.7 ml) was significantly reduced in all patients when compared with pretreatment sizes (420.8 +/- 276.4, P less than 0.05). Side effects included hot flashes (78%), vaginal dryness (32%), and transient frontal headaches (55%). All patients reported partial or complete relief from their symptomatic leiomyomata. Uterine volume at the conclusion of follow-up (345.4 +/- 195.7 ml) was greater than at the conclusion of therapy. Menses resumed in all patients within 4 to 8 weeks. In conclusion, GnRH-a therapy does not provide definitive therapy for symptomatic uterine leiomyomata but is effective in reducing the size of leiomyomata as a temporary measure. Gonadotropin-releasing hormone agonist therapy may be useful as an adjunct before myomectomy or hysterectomy and deserves further investigation.

From 1979 to 1985, 18 patients who were found to have proximal tubal obstruction by hysterosalpingography and laparoscopic chromopertubation underwent resection of the obstructed tubal segment and reimplantation or microanastomosis. Resected tubal segments were studied histologically, and in 11 of the 18 cases no tubal occlusion could be demonstrated. A variety of histologic abnormalities were noted, however, including six cases in which the tubal lumen contained an amorphous material of unknown etiology, often appearing to form a cast of the tube. Such "plugs," which the authors believe to be previously unreported, have no clearly established clinical significance at present. However, if they cause tubal occlusion, this would explain several previously published findings, and would also have implications for therapy.

The authors present their initial results with the hemizona assay (HZA), which was developed to predict the fertilizing potential of spermatozoa. The HZA uses the matching halves of a human zona pellucida from a nonfertilizable and nonliving oocyte, providing an internal control on zona-to-zona variability. Maximal binding of human sperm to the hemizona usually occurred after 4 to 5 hours of coincubation. Sperm from fertile men exhibited significantly higher binding capacity to hemizonae compared with sperm from men who had fertilization failure during in vitro fertilization (IVF) treatment. The HZA index is calculated as follows: (bound sperm from subfertile male) divided by (bound sperm from fertile male) X 100. These findings demonstrate that the HZA may be a useful diagnostic tool in male infertility evaluations.

The hemizona assay (HZA) was used in the monkey model to investigate sperm binding to the zona pellucida and to evaluate binding patterns according to various stages of oocyte development. Adult cynomolgus monkeys were superovulated with human menopausal gonadotropin. The oocytes were retrieved by laparoscopy, stored in salt solution, then cut into hemizonae by micromanipulation. Metaphase II oocytes showed significantly tighter binding than prophase I oocytes (P less than 0.001). Metaphase I oocytes showed intermediate binding, significantly different from the other groups (P less than 0.01). It is concluded that: (1) This study demonstrates the feasibility of HZA as a test to evaluate sperm/zona interactions in the monkey, using standards reported for human studies. (2) Oocyte meiotic competence seems to be accompanied by an increase in zona-binding properties.

Because the size of leiomyomata uteri often decreases significantly after menopause, the authors elected to employ a long-acting gonadotropin hormone-releasing hormone analog (GnRH-alpha) (imbzl-D-His6-Pro9-Net-GnRH) to create a state of pseudomenopause in six patients with leiomyomata uteri diagnosed on the basis of pelvic examination and confirmed by pelvic ultrasonography. Patients received daily, subcutaneous injections of GnRH-alpha (4 micrograms X kg-1 X 24 hour-1) for 6 months. Uterine size (13.8 +/- 4 weeks [mean +/- standard deviation (SD), n = 6]) was determined by pelvic examination and uterine volume (533.9 +/- 394 ml [mean +/- SD, n = 6]) was determined by pelvic ultrasonography before medical therapy was begun. They observed a decrease in uterine size by pelvic examination within 4 weeks of the initiation of therapy, and all patients experienced a decrease in uterine size (9.5 +/- 4 weeks [mean +/- SD, n = 6]) (P less than 0.05) within 8 weeks of initiation of therapy. After 6 months of therapy, uterine size was 229.5 +/- 145 ml (mean +/- SD, n = 6). During treatment, plasma estrogen concentrations were assessed intermittently (every 1 to 4 weeks) and remained less than 4 pg X ml-1 throughout the period of therapy. All six patients have discontinued therapy. There has been no increase in uterine size in these patients for a period from 3 to 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

In the present study we sought to compare levels of PAPP-A and hCG produced by different types of pregnancy: normal, ectopic, threatened abortion and molar pregnancy after evacuation. The gestations ranged from 13 to 122 days. Serum levels of both PAPP-A and hCG were measured and compared. Chi squares analysis were predictive only for increasing trends in hCG as well as decreasing trends of both hCG and PAPP-A. Analysis of variance and linear discriminant function used to evaluate results suggested that PAPP-A did not improve predictability of hCG. The values of PAPP-A levels for the postevacuation molar pregnancies barely exceeded the lower limit of detection; thus, no meaningful comparisons could be made.

The hemizona assay (HZA) was used in a prospective, blinded study to assess the relationship between tight sperm binding in the HZA and sperm fertilizing ability in in vitro fertilization (IVF). In each controlled assay, the authors compared sperm binding of proven fertile men with that of patients undergoing IVF. Human oocytes stored in a salt solution were used in the study, and binding results were correlated with the fertilization rate of preovulatory oocytes during IVF. Patients with poor fertilization rates in IVF had significantly lower binding than those cases with successful fertilization (7.3 +/- 1.4 versus 62.1 +/- 10.9, respectively; mean +/- standard error, P less than 0.02). Based on current standards, the HZA was able to predict fertilization accurately in 26 of 28 cases (sensitivity of 83%, specificity of 95%, positive predictive value of 83%). The authors conclude that the HZA is a valuable tool for evaluating dysfunctional sperm-zona pellucida binding, with good predictive value for fertilization in vitro.

Because methylene blue exhibits germicidal, oxidation, and reduction properties, the authors asked whether this agent causes adverse effects on gametes, embryos, and/or secretions of the reproductive tract. Time- and dose-dependent inhibition of human sperm motility by methylene blue was observed, as was growth inhibition of 2-cell mouse embryos. Furthermore, the presence of methylene blue in uterine, fallopian tube, and peritoneal fluids altered protein mobility in polyacrylamide gels, and yielded apparent values of follicle-stimulating hormone and estradiol up to 260% of actual values (P less than 0.05). These data suggest that the presence of methylene blue in reproductive tract fluids may provide a false impression of their biochemical and biophysical compositions, and that the use of methylene blue as a chromopertubation agent be conducted with appropriate awareness.