Removal of uterine polyps: clinical management and surgical approach.

Endometrial polyps have a reported prevalence from 7.8% up to 30% and are one of the most cost-consuming gynecological conditions for our specialty. There are strong practitioner beliefs that surgical removal of endometrial polyps is highly beneficial, particularly for those with abnormal uterine bleeding and infertility. Additionally, polypectomy is indicated to reduce the risk of malignancy. Transvaginal ultrasound is the first-line diagnostic option for detection of endometrial polyps, while sonohysterography has similar accuracy as hysteroscopy in the diagnostic confirmation. Blind dilatation and curettage is not recommended for polyp removal; rather, hysteroscopy in the operating room and office setting using small-diameter hysteroscopic equipment is the standard approach. This can be performed without anesthesia in most women. While hysteroscopy is an effective method for polypectomy with a low complication rate, it is unknown whether this is truly beneficial for reproductive-age women with infertility and prior assisted reproduction therapy. The risk of malignancy in women with postmenopausal bleeding justifies the necessity of polypectomy with histologic tissue examination. In asymptomatic women, the risk of malignancy is low, and there are no known benefits of polyp removal in the prevention of malignant transformation. Cost-effective studies remain to be done to provide us with the optimal approach to endometrial polyps including the management of asymptomatic and/or infertile women, ideal location including office-based or the operating room setting, complication prevention including intrauterine adhesions, and recurrence issues.

Congenital Uterine Malformation by Experts (CUME): diagnostic criteria for T-shaped uterus.

OBJECTIVES: To identify uterine measurements that are reliable and accurate to distinguish between T-shaped and normal/arcuate uterus, and define T-shaped uterus, using Congenital Uterine Malformation by Experts (CUME) methodology, which uses as reference standard the decision made most often by several independent experts. METHODS: This was a prospectively planned multirater reliability/agreement and diagnostic accuracy study, performed between November 2017 and December 2018, using a sample of 100 three-dimensional (3D) datasets of different uteri with lateral uterine cavity indentations, acquired from consecutive women between 2014 and 2016. Fifteen representative experts (five clinicians, five surgeons and five sonologists), blinded to each others' opinions, examined anonymized images of the coronal plane of each uterus and provided their independent opinion as to whether it was T-shaped or normal/arcuate; this formed the basis of the CUME reference standard, with the decision made most often (i.e. that chosen by eight or more of the 15 experts) for each uterus being considered the correct diagnosis for that uterus. Two other experienced observers, also blinded to the opinions of the other experts, then performed independently 15 sonographic measurements, using the original 3D datasets of each uterus. Agreement between the diagnoses made by the 15 experts was assessed using kappa and percent agreement. The interobserver reliability of measurements was assessed using the concordance correlation coefficient (CCC). The diagnostic test accuracy was assessed using the area under the receiver-operating-characteristics curve (AUC) and the best cut-off value was assessed by calculating Youden's index, according to the CUME reference standard. Sensitivity, specificity, negative and positive likelihood ratios (LR- and LR+) and post-test probability were calculated. RESULTS: According to the CUME reference standard, there were 20 T-shaped and 80 normal/arcuate uteri. Individual experts recognized between 5 and 35 (median, 19) T-shaped uteri on subjective judgment. The agreement among experts was 82% (kappa = 0.43). Three of the 15 sonographic measurements were identified as having good diagnostic test accuracy, according to the CUME reference standard: lateral indentation angle (AUC = 0.95), lateral internal indentation depth (AUC = 0.92) and T-angle (AUC = 0.87). Of these, T-angle had the best interobserver reproducibility (CCC = 0.87 vs 0.82 vs 0.62 for T-angle vs lateral indentation depth vs lateral indentation angle). The best cut-off values for these measurements were: lateral indentation angle ≤ 130° (sensitivity, 80%; specificity, 96%; LR+, 21.3; LR-, 0.21), lateral indentation depth ≥ 7 mm (sensitivity, 95%; specificity, 77.5%; LR+, 4.2; LR-, 0.06) and T-angle ≤ 40° (sensitivity, 80%; specificity, 87.5%; LR+, 6.4; LR-, 0.23). Most of the experts diagnosed the uterus as being T-shaped in 0% (0/56) of cases when none of these three criteria was met, in 10% (2/20) of cases when only one criterion was met, in 50% (5/10) of cases when two of the three criteria were met, and in 93% (13/14) of cases when all three criteria were met. CONCLUSIONS: The diagnosis of T-shaped uterus is not easy; the agreement among experts was only moderate and the judgement of individual experts was commonly insufficient for accurate diagnosis. The three sonographic measurements with cut-offs that we identified (lateral internal indentation depth ≥ 7 mm, lateral indentation angle ≤ 130° and T-angle ≤ 40°) had good diagnostic test accuracy and fair-to-moderate reliability and, when applied in combination, they provided high post-test probability for T-shaped uterus. In the absence of other anomalies, we suggest considering a uterus to be normal when none or only one criterion is met, borderline when two criteria are met, and T-shaped when all three criteria are met. These three CUME criteria for defining T-shaped uterus may aid in determination of its prevalence, clinical implications and best management and in the assessment of post-surgical morphologic outcome. The CUME definition of T-shaped uterus may help in the development of interventional randomized controlled trials and observational studies and in the diagnosis of uterine morphology in everyday practice, and could be adopted by guidelines on uterine anomalies to enrich their classification systems. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Septate uterus according to ESHRE/ESGE, ASRM and CUME definitions: association with infertility and miscarriage, cost and warnings for women and healthcare systems.

OBJECTIVES: To estimate the differences in frequency of diagnosis of septate uterus using three different definitions and determine whether these differences are significant in clinical practice, and to examine the association between diagnosis of septate uterus, using each of the three definitions, and infertility and/or previous miscarriage as well as the cost of allocation to surgery. METHODS: This was a secondary analysis of data from a prospective study of 261 consecutive women of reproductive age attending a private clinic focused on the diagnosis and treatment of congenital uterine malformations. Reanalysis of the datasets was performed according to three different means of defining septate uterus: following the recommendations of the American Society for Reproductive Medicine (ASRM), a 2016 update of those of the American Fertility Society from 1988 (ASRM-2016: internal fundal indentation depth ≥ 1.5 cm, angle of internal indentation < 90° and external indentation depth < 1 cm); following the recommendations of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE/ESGE), published in 2013 and reaffirmed in 2016 (ESHRE/ESGE-2016: internal fundal/uterine indentation depth > 50% of uterine-wall thickness and external indentation depth < 50% of uterine-wall thickness, with uterine-wall thickness measured above interostial/intercornual line); and using a definition published last year which was based on the decision made most often by a group of experts (Congenital Uterine Malformation by Experts; CUME) (CUME-2018: internal fundal indentation depth ≥ 1 cm and external fundal indentation depth < 1 cm). We compared the rate of diagnosis of septate uterus using each of these three definitions and, for each, we estimated the association between the diagnosis and infertility and/or previous miscarriage, and anticipated the costs associated with their implementation using a guesstimation method. RESULTS: Although 32.6% (85/261) of the subjects met the criteria for one of the three definitions of septate uterus, only 2.7% (7/261) of them were defined as having septate uterus according to all three definitions. We diagnosed significantly more cases of septate uterus using ESHRE/ESGE-2016 than using ASRM-2016 (31% vs 5%, relative risk (RR) = 6.7, P < 0.0001) or CUME-2018 (31% vs 12%, RR = 2.6, P < 0.0001) criteria. We also observed frequent cases that could not be classified definitively by ASRM-2016 (gray zone: neither normal/arcuate nor septate; 6.5%). There were no significant differences (P > 0.05) in the prevalence of septate uterus in women with vs those without infertility according to ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) or CUME-2018 (11% vs 12%). Septate uterus was diagnosed significantly more frequently in women with vs those without previous miscarriage according to ASRM-2016 (11% vs 3%; P = 0.04) and CUME-2018 (22 vs 10%; P = 0.04), but not according to ESHRE/ESGE-2016 (42% vs 28%; P = 0.8) criteria. Our calculations showed that global costs to the healthcare system would be highly dependent on the criteria used in the clinical setting to define septate uterus, with the costs associated with the ESHRE/ESGE-2016 definition potentially being an extra US$ 100-200 billion over 5 years in comparison to ASRM-2016 and CUME-2018 definitions. CONCLUSIONS: The prevalence of septate uterus according to ESHRE/ESGE-2016, ASRM-2016 and CUME-2018 definitions differs considerably. An important limitation of the ASRM classification, which needs to be addressed, is the high proportion of unclassifiable cases originally named, by us, the 'gray zone'. The high rate of overdiagnosis of septate uterus according to ESHRE/ESGE-2016 may lead to unnecessary surgery and therefore unnecessary risk in these women and may impose a considerable financial burden on healthcare systems. Efforts to define clinically meaningful and universally applicable criteria for the diagnosis of septate uterus should be encouraged. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Útero septo según las definiciones de ESHRE/ESGE, ASRM y CUME: la relación con la infertilidad y el aborto espontáneo, el costo y advertencias para las mujeres y los sistemas de salud OBJETIVO: Evaluar el rendimiento de la velocidad sistólica máxima de la arteria cerebral media fetal (MCA-PSV, por sus siglas en inglés) ≥1,5 múltiplos de la mediana (MdM) para la predicción de la anemia moderada-severa en fetos sometidos a transfusión y no sometidos. MÉTODOS: Se realizó una búsqueda sistemática para identificar estudios observacionales relevantes reportados en el período 2008-2018 que evaluaron el rendimiento de la MCA-PSV, utilizando un umbral de 1,5MdM para la predicción de la anemia fetal. El diagnóstico de la anemia fetal mediante la toma de muestras de sangre fue el estándar de referencia. Se utilizaron modelos de efectos aleatorios para la elaboración de una curva jerárquica resumen de las características operativas del receptor (hSROC, por sus siglas en inglés). Se realizaron análisis de subgrupos y metarregresión, según el número de transfusiones intrauterinas previas. RESULTADOS: En el metaanálisis se incluyeron doce estudios y 696 fetos. El área bajo la curva (ABC) hSROC para la anemia moderada-severa fue del 83%. La sensibilidad y especificidad agrupadas (IC 95%) fueron del 79% (70-86%) y 73% (62-82%), respectivamente, y los cocientes de verosimilitud positivos y negativos fueron 2,94 (IC 95%: 2,13-4,00) y 0,272 (IC 95%: 0,188-0,371). Cuando solo se consideraron los fetos no sometidos a transfusión, la predicción mejoró, pues se logró un ABC del 87%, una sensibilidad del 86% (IC 95%: 75-93%) y una especificidad del 71% (IC 95%: 49-87%). Se observó una disminución en la sensibilidad de la predicción de la anemia moderada-severa mediante la MCA-PSV ≥1.5MdM (estimación, -5,5% (IC 95%: -10,7 a -0,3%), P=0,039) en función del aumento del número de transfusiones previas. CONCLUSIONES: El uso de la MCA-PSV ≥1.5MdM para la predicción de la anemia moderada-severa en fetos no sometidos a transfusión muestra una precisión moderada (86% de sensibilidad y 71% de especificidad), que disminuye con el aumento del número de transfusiones intrauterinas.

Congenital Uterine Malformation by Experts (CUME): better criteria for distinguishing between normal/arcuate and septate uterus?

OBJECTIVES: To assess the level of agreement between experts in distinguishing between septate and normal/arcuate uterus using their subjective judgment when reviewing the coronal view of the uterus from three-dimensional ultrasound. Another aim was to determine the interobserver reliability and diagnostic test accuracy of three measurements suggested by recent guidelines, using as reference standard the decision made most often by experts (Congenital Uterine Malformation by Experts (CUME)). METHODS: Images of the coronal plane of the uterus from 100 women with suspected fundal internal indentation were anonymized and provided to 15 experts (five clinicians, five surgeons and five sonologists). They were instructed to indicate whether they believed the uterus to be normal/arcuate (defined as normal uterine morphology or not clinically relevant degree of distortion caused by internal indentation) or septate (clinically relevant degree of distortion caused by internal indentation). Two other observers independently measured indentation depth, indentation angle and indentation-to-wall-thickness (I:WT) ratio. The agreement between experts was assessed using kappa, the interobserver reliability was assessed using the concordance correlation coefficient (CCC), the diagnostic test accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) and the best cut-off value was assessed using Youden's index, considering as the reference standard the choice made most often by the experts (CUME). RESULTS: There was good agreement between all experts (kappa, 0.62). There were 18 septate and 82 normal/arcuate uteri according to CUME; European Society of Human Reproduction and Embryology (ESHRE)-European Society for Gynaecological Endoscopy (ESGE) criteria (I:WT ratio > 50%) defined 80 septate and 20 normal/arcuate uteri, while American Society for Reproductive Medicine (ASRM) criteria defined five septate (depth > 15 mm and angle < 90°), 82 normal/arcuate (depth < 10 mm and angle > 90°) and 13 uteri that could not be classified (referred to as the gray-zone). The agreement between ESHRE-ESGE and CUME was 38% (kappa, 0.1); the agreement between ASRM criteria and CUME for septate was 87% (kappa, 0.39), and considering both septate and gray-zone as septate, the agreement was 98% (kappa, 0.93). Among the three measurements, the interobserver reproducibility of indentation depth (CCC, 0.99; 95% CI, 0.98-0.99) was better than both indentation angle (CCC, 0.96; 95% CI, 0.94-0.97) and I:WT ratio (CCC, 0.92; 95% CI, 0.90-0.94). The diagnostic test accuracy of these three measurements using CUME as reference standard was very good, with AUC between 0.96 and 1.00. The best cut-off values for these measurements to define septate uterus were: indentation depth ≥ 10 mm, indentation angle < 140° and I:WT ratio > 110% . CONCLUSIONS: The suggested ESHRE-ESGE cut-off value overestimates the prevalence of septate uterus while that of ASRM underestimates this prevalence, leaving in the gray-zone most of the uteri that experts considered as septate. We recommend considering indentation depth ≥ 10 mm as septate, since the measurement is simple and reliable and this criterion is in agreement with expert opinion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Gestational carrier BMI and reproductive, fetal and neonatal outcomes: are the risks the same with increasing obesity?

OBJECTIVE: Data suggest that female obesity impairs uterine receptivity and increases the risk of fetal and neonatal mortality. We analyzed the reproductive outcomes of gestational carriers (GCs) undergoing donated oocytes and assisted reproductive technology according to body mass index (BMI). DESIGN: A retrospective analysis of 163 GCs undergoing 226 in vitro fertilization (IVF) and embryo transfer cycles. METHODS: GCs undergoing in vitro fertilization and embryo transfer cycles were analyzed and divided according to their BMI (healthy weight: 20-24.9 kg m(-2) (n=77 in 114 cycles); overweight: 25-29.9 kg m(-)(2) (n=55 in 71 cycles); and obese: 30-35 kg m(-)(2) (n=31 in 41 cycles)). All GCs underwent a complete medical evaluation and were cleared for pregnancy before being selected. Overweight and obese GCs also underwent a metabolic screening, including an oral glucose tolerance test and lipid profile. The main outcomes measured were clinical pregnancy and live birth rates, antenatal and neonatal outcomes. RESULTS: Clinical pregnancy and live birth rates were similar despite increasing BMI. There were no statistically significant differences in the implantation rates, clinical pregnancy rates or live birth rates per embryo transfer among patients in the three BMI groups. In the healthy weight, overweight and obese GCs, the clinical pregnancy rates per GC were 72%, 84% and 79%, and per embryo transfer rates were 52%, 49% and 56%, respectively; P=NS. The live birth rates per GC were 70%, 84% and 75%, and per embryo transfer rates were 50%, 49% and 53%, respectively; P=NS. Twin rates were similar between the groups (35%, 31% and 29%, respectively; P=NS). There were no differences in gestational diabetes, preterm admissions or cesarean section rates. Neonatal intensive care unit admissions were similar (11%, 13% and 12%, respectively; P=NS), and no maternal, neonatal or infant mortality occurred. CONCLUSIONS: These data show that increasing obesity does not impair the reproductive outcome in GC cycles. Larger sample size is indicated to verify these findings. Furthermore, this study suggests that the standard metabolic screening used for GCs may lead to selection of healthier patients compared with women of comparable BMI who conceive outside of a fertility clinic setting, indicating the metabolic profile, rather than BMI, may better explain differences in pregnancy outcomes.

Clinical outcomes using a flexible regimen of GnRH-antagonists and a 'step-up' of additional gonadotropins in donor oocyte cycles.

OBJECTIVE: To assess the impact of serum estradiol upon oocyte donor cycle stimulation characteristics and clinical outcomes using flexible GnRH-antagonist (GnRH-ant) with additional FSH supplementation. RESEARCH DESIGN AND METHODS: A retrospective chart review of 99 oocyte donor cycles using ovarian hyperstimulation with recombinant FSH (rFSH) and GnRH-ant was analyzed. Following discontinuation of oral contraceptives, controlled ovarian hyperstimulation was begun using rFSH (150-300 IU daily). GnRH-ant (ganirelix, Organon) and an additional 75 IU of FSH/day were begun when lead follicles were 13-14 mm in greatest diameter. Cycles were analyzed based on serum estradiol response following administration of GnRH-ant (Group 1: progressive rise and Group 2: no rise or a decline). Primary endpoints were cycle stimulation characteristics based on serum estradiol following GnRH-ant, clinical pregnancy and implantation rates. RESULTS: A decline in serum estradiol was seen after GnRH-ant administration in 45% of cycles. Clinical pregnancy rates per transfer (70 vs. 72%) and implantation rates (43 vs. 56%) were similar for each group. CONCLUSION: Flexible regimens of GnRH-ant even with additional rFSH in a 'step-up' fashion frequently result in a decline in serum estradiol during ovulation induction. While our study is non-randomized, it does not appear to result in any adverse affect in clinical outcomes in donor oocyte cycles.

A retrospective comparison of clinical outcomes and satisfaction using reconstituted recombinant gonadotropins (rFSH) or cartridge rFSH with a pen device in donor oocyte cycles.

BACKGROUND: Use of recombinant follicle stimulating hormone (rFSH) in a cartridge pen device offers obvious benefits for donor oocyte cycles including the administration of fewer and more patient-friendly injectable medications. METHODS: In a University-based IVF program, a total of 98 oocyte donor cycles using rFSH either reconstituted or as a pen device given to 118 recipients (eight split cycles) were retrospectively reviewed. Following discontinuation of oral contraceptive, controlled ovarian hyperstimulation was begun using either reconstituted rFSH (n = 19) or rFSH with a cartridge pen device (n = 79) (150-300 IU qd). GnRH-antagonists (Ganirelix, Organon) and an additional 75 IU of rFSH/day were begun when lead follicles were 13-14 mm in greatest diameter. The primary endpoints analyzed included cycle stimulation characteristics for each donor group and donor medication tolerance assessment with respect to each rFSH formulation, while secondary outcome measures included clinical pregnancy and implantation rates. RESULTS: Oocyte donors using the pen required significantly less rFSH (2734 IU vs. 3276 IU, p < 0.05) and scored significantly higher medication tolerance scores (3.9 +/- 0.4 vs. 3.1 +/- 0.6, p < 0.05). No other differences in cycle stimulation for oocyte donors and clinical outcomes for recipients were seen including pregnancy rates (pen, 77% vs. reconstituted, 55%, p - NS) and clinical pregnancy rates (61% vs. 45%, p - NS). However, significantly greater implantation rates (57% vs. 31%, p < 0.01) occurred in the pen group. CONCLUSION: Compared to reconstituted formulations, the pen device results in lower gonadotropin requirements and provides a simplified dosing method with better tolerance.

Saline contrast sonohysterography and directed extraction, resection and biopsy of intrauterine pathology using a Uterine Explora Curette.

OBJECTIVE: To assess the utility of an endometrial sampling device, the Uterine Explora Curette, with concomitant saline contrast sonohysterography (SCSH) for ultrasound-directed extraction, resection and biopsy of endometrial pathology. METHODS: Use of the Uterine Explora Curette was prospectively evaluated in 20 women with either infertility (n = 14), recurrent miscarriage (n = 2) or peri-/postmenopausal bleeding (n = 4). Findings on SCSH were compared with those on pathological analysis. RESULTS: In all 20 cases the Uterine Explora Curette was used successfully during SCSH to treat endometrial filling defects. The procedure was well tolerated, with an average time from start to finish of 10 (range, 2-23) min. It was without complications, and appeared to remove or biopsy adequately endometrial filling defects in most patients, obviating the need for hysteroscopy. CONCLUSIONS: In properly selected patients, directed extraction, resection and biopsy using the Uterine Explora Curette during SCSH appears to be an effective and easy method for treating intrauterine pathology and provides a cost-effective alternative to operative hysteroscopy.

GnRH antagonists followed by a decline in serum estradiol results in adverse outcomes in donor oocyte cycles.

BACKGROUND: The aim of this retrospective study was to assess clinical outcomes using GnRH antagonists in oocyte donation cycles. METHODS: Between July 2000 and June 2001, 40 recipient cycles generated from donor oocytes were evaluated. Controlled ovarian hyperstimulation (COH) was started on cycle day 2 using recombinant gonadotrophins (225 IU daily). GnRH antagonist was started on cycle day 6 of COH. All recipients were synchronized to donors using GnRH agonist followed by estrogen and progesterone supplementation. Main outcome measures were days of stimulation (DOS), number of ampoules used, peak serum estradiol, number of oocytes, fertilization rate, embryo score, clinical on-going pregnancy rate and implantation rate. RESULTS: Thirty-seven donor cycles (93%) underwent oocyte retrieval, resulting in 36 embryo transfers. Fourteen cycles (35%) had decreased serum estradiol after initiation of GnRH antagonist. No differences were seen in numbers of FSH ampoules, DOS, peak serum estradiol, number of retrieved oocytes, fertilization rate and embryo quality. However, clinical pregnancy rate per initiated cycle [14% (2/14) versus 54% (14/26)], ongoing pregnancy rate per initiated cycle [7% (1/14) versus 46% (12/26)] and implantation rate (4 versus 24%) were all significantly less (P <0.05) following a decrease in serum estradiol after initiation of GnRH antagonist. No clinical predictor, including donor age, basal day 2 FSH or estradiol, ovarian morphology or serum estradiol prior to GnRH antagonist, was predictive of a decline in serum estradiol following GnRH antagonist. CONCLUSION: These data demonstrate an adverse effect on clinical outcome in cycles, resulting in a decline in serum estradiol after GnRH antagonist administration. This effect was unpredictable and provided a simplified protocol for oocyte donation cycles; nonetheless, further study is needed to clarify the adverse effects of GnRH antagonists in oocyte donation cycles.

Operative ultrasound using an echogenic loop snare for intrauterine pathology.

A technique for resecting intrauterine tissue was performed in nine women, each of whom had intrauterine pathology on sonohysterogram. The uterine cavity was entered with a 12F intrauterine access catheter with a 3-ml balloon that was placed in the cervical canal or lower uterine segment. A 5F echogenic loop snare was passed through the access catheter and resection was attempted under ultrasound guidance. Biopsy samples underwent pathologic examination for definitive diagnosis. Seven of nine patients had adequate resection or biopsy tissue, but in two the loop snare could not secure the base of the lesion. All procedures were well tolerated. Average operating time was about 27 minutes (range 18-43 min), with no complications. Operative ultrasound makes it possible to resect and biopsy intrauterine pathology. In selected patients, this procedure is a cost-effective alternative to hysteroscopy.

Comparison of sonohysterography and hysteroscopy: lessons learned and avoiding pitfalls.

We compared ultrasound images of the uterine cavity obtained by sonohysterography (SHG) with those of hysteroscopy in an attempt to avoid inaccurate interpretations. Women referred for abnormal bleeding or infertility underwent SHG before treatment. Those with an abnormal study underwent hysteroscopy for confirmation and treatment. Abnormal SHG studies are frequent, with false positive images including blood clots, mucus plugs, and shearing of normal endometrium relatively common. Uterine pathology generally seen on SHG, including anomalies, polyps, and myomas, is consistent with that seen at hysteroscopy. Performing intraoperative SHG concomitantly with hysteroscopy adds value due to SHG's three-dimensional images to confirm depth of pathology and false negative hysteroscopy findings.

Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope.

Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure. In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5- to 10-day time segment (P=0.018) and the 10- to 15-day time segment (P=0.045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10- to 15-day time period (P=0.058). In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0.043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy. Antibody B152 was produced using a choriocarcinoma-derived hCG (C5), which was hyperglycosylated at both N- and O-linked sites and was 100% nicked at position beta(47-48). Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the same size as later pregnancy hCG as judged by SDS gel electrophoresis. A series of Western blot analyses and immunoassays conducted with the samples either non-reduced or reduced showed that B152 is directed to a linear epitope located in the COOH-terminal peptide region of the beta subunit. This indicated that only the O-glycan groups and not the N-linked glycans are part of the antibody epitope.

Assessing the influence of payment on motivations of women participating as oocyte donors.

We report on the motivations of potential ovum donors entering an assisted reproduction program and discuss the potential ramifications of escalating payments to donors. From July 1995 to July 1998, recruitment of ovum donors was directed at healthy women between 21 and 34 years of age. Financial remuneration for services rendered was USD 2,500 from July 1995 through March 1998 and increased to USD 5,000 after that. Donors were screened and consented according to established SART guidelines. The demographic background of the women was similar for women paid USD 2,500 to those receiving USD 5,000. The financial motivation was greater in those receiving USD 5,000 (68%) than USD 2,500 (39%). Some form of expressed altruism was similarly present in both groups (USD 5,000 90%, and USD 2,500 91%). However, altruism expressed as the sole motivation occurred more in those receiving USD 2,500 (61%) compared to USD 5,000 (32%). Financial reimbursement has escalated for the services of ovum donors in order to maintain the increasing demand. While money has become a dominant factor motivating ovum donors, its seductive nature requires even greater attention to adequate informed consent. Young donors may be unable to adequately weigh the risks of ovarian hyperstimulation and oocyte retrieval against the monetary reward.

Controlled ovarian hyperstimulation. Relationship of early serum E2 levels to the ultimate response of oocyte donors.

OBJECTIVE: To assess the predictive value of measuring serum day 5 E2 and in vitro fertilization (IVF) cycle outcome of oocyte donors undergoing controlled ovarian hyperstimulation (COH). STUDY DESIGN: Retrospective data analysis. RESULTS: Day 5 E2 significantly correlated with the peak serum E2 and number of retrieved mature oocytes. The pregnancy rates associated with stimulated day 5 E2 > 70 pg/mL were significantly greater than in cycles with levels < 70 pg/mL (58%, 71/123, versus 25%, 15/60; P < .05). CONCLUSION: The cycle performance of an oocyte donor can be predicted by measuring cycle day 5 serum E2 during COH. Poor-prognosis cycles can be identified and discontinued, saving patients and the program unnecessary exspense.

Testicular sperm aspiration (TESA) and its application in oocyte donation.

This study was conducted to assess the outcomes of TESA in women undergoing oocyte donation. Descriptive reports from a university IVF practice were reviewed to evaluate the outcomes of women (n = 10) who underwent 12 cycles of ovum donation and required testicular sperm aspiration due to obstructive azoospermia (n = 6) and nonobstructive azoospermia (n = 4). Percutaneous needle aspiration of the testes was performed prior to oocyte retrieval to recover sperm, and intracytoplasmic sperm injection was subsequently performed on the donated oocytes. Fertilization was documented 16-18 h later and transcervical embryo transfer performed 72 h postretrieval. Successful retrieval of testicular spermatozoa utilizing the percutaneous technique was achieved in all 12 cycles. All cycles resulted in an ET with the achievement of 7 (58%) pregnancies, of which 5 (42%) are ongoing or delivered. The individual embryo implantation rate was 18.4% (9/49). Two cycles (16.6%) produced supernumerary embryos for cryopreservation. TESA represents a simple procurement technique associated with minimal morbidity. It may be offered even in cases of nondestructive azoospermia.

Echosight patton coaxial catheter-guided hysteroscopy.

Two women requiring assisted reproduction had cervical stenosis on diagnostic evaluation. Office hysteroscopy was performed with paracervical block supplemented with mild intravenous sedation. When cervical pathology precluded placement of a diagnostic hysteroscopy, an Echosight Patton coaxial catheter with an outer echogenic sheath (5.7F) and inner 0.018-inch diameter guidewire with coude tip was introduced transcervically. Intraoperative transvaginal ultrasound was performed to ensure proper placement into the uterine cavity. When the uterine cavity was identified, cervical pathology was corrected with a VersaPoint electrosurgical electrode with bipolar coagulation through an operative hysteroscope. Concomitant diagnostic laparoscopy was not necessary. Echosight Patton coaxial catheter-guided ultrasound is a reassuring method to confirm hysteroscopic placement.

Normal ovulatory women with polycystic ovaries have hyperandrogenic pituitary-ovarian responses to gonadotropin-releasing hormone-agonist testing.

Women with polycystic ovary syndrome (PCOS) have chronic anovulation and hyperandrogenism and frequently have abnormalities in their lipid profiles and insulin/insulin-like growth factor axis that increase their lifetime risk for cardiovascular disease. Normal ovulatory women may have polycystic ovaries on ultrasonography and yet lack the clinical features of PCOS. To further explore whether ovulatory women without clinical/biochemical hyperandrogenism but with polycystic appearing ovaries (ov-PAO) have subclinical features of PCOS, we prospectively characterized 26 ov-PAO women and matched them by age and body mass index to 25 ovulatory women with normal appearing ovaries (ov-NAO) and to 22 women with PCOS. After an overnight fast, all women had baseline endocrine and metabolic assessments. In addition, a subset of each group of women underwent GnRH-agonist (leuprolide acetate 1 mg s.c.) testing, ACTH stimulation, and an insulin tolerance test (ITT). At baseline, ov-PAO and ov-NAO women had similar endocrine profiles (LH, LH:FSH, androstenedione, and DHEAS). Compared with ov-NAO, 31% of ov-PAO women had reduced glucose responses after insulin (K(itt)), suggesting mild insulin resistance, and 35% had high density lipoprotein levels below 35 mg/dL, a level considered to represent significant cardiovascular risk. After GnRH-agonist, ov-PAO women had response patterns in LH, total testosterone, and 17-hydroxyprogesterone (17-OHP) that were intermediate between ov-NAO and women with PCOS. Ovarian responses were above the normal range in 30-40% of women with ov-PAO. In ov-PAO, peak responses of LH after leuprolide correlated with triglyceride levels (P < 0.05) and peak responses of 17-OHP correlated inversely with Kitt values (P < 0.05). No significant differences were noted with ACTH testing. In conclusion, occult biochemical ovarian hyperandrogenism may be uncovered using GnRH-agonist in ovulatory women with ov-PAO, while adrenal responses remain normal. Subtle metabolic abnormalities may also be prevalent.