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To compare standard density gradient/centrifugation sperm preparation with a novel non-centrifugation-based dual-chamber capillary dish in efficiency for motile human sperm separation, ~3 mL fresh ejaculate specimens was obtained from 21 men (median age = 32 years, range = 26-42 years) undergoing infertility evaluation. For each specimen, half of the sample was processed with a standard 45%/90% density gradient preparation (PureSperm, Nidacon International, Gothenburg, Sweden) followed by semen analysis. The other half was incubated in the Zech glass capillary dish (Astromedtec, Salzburg, Austria) consisting of 2 concentric wells overlaid by a U-ring and coverglass. After ~3 h, a 1-mL sample was taken from the central chamber and analyzed. Percentage motile sperm recovery, absolute (motile) cell number, and path velocities were compared for spermatozoa obtained from both methods. Both techniques reduced overall sperm concentration while enriching specimens with more motile spermatozoa. A trend towards higher % recovery of motile spermatozoa (p = .264) was observed with the Zech device, but at a cost of fewer absolute numbers of higher velocity cells (p = .004). The Zech device, therefore, localized a very small population of motile sperm without exposure to centrifugation stress, which has been considered potentially harmful to spermatozoa. This technique could theoretically improve efficiency by reducing time required to identify motile cells in in vitro fertilization where intracytoplasmic sperm injection is planned. However, refinements in incubation interval and suspension volumes are needed before this technique can be considered comparable to the density gradient method in recovering sperm for use in intrauterine insemination. [ABSTRACT FROM AUTHOR]

To assess the association of zona pellucida micromanipulation and subsequent development of monozygotic twins, cases of assisted embryo hatching (AH) and intracytoplasmic sperm injection (ICSI) were identified and related to treatment type, implantation and zygosity data. Embryology records from all patients undergoing in-vitro fertilization (IVF) at this centre from January 1995 to March 1998 were reviewed. In this study, 3546 transfer cycles were completed, with clinical pregnancy established in 1911 (54% per transfer) patients undergoing a single IVF cycle. These pregnancies occurred in 1674 (88%) IVF cycles, 120 (6%) donor oocyte cycles (DER), and 117 (6%) frozen embryo transfer (FET) cycles. During the study period, 23 cases of monozygotic (MZ) twins were identified, representing an overall frequency of 1.2%. Chorionicity was determined by transvaginal ultrasound at 7 weeks when the number of embryos transferred was less than the number of fetal heart-beats, or when >1 fetal heartbeat per gestational sac was seen. Zygosity was confirmed by placental evaluation at delivery, and corroborated the antenatal diagnosis in all cases. Among IVF study patients the frequency of MZ twinning was not statistically different between zona manipulated and zona intact subgroups. While this investigation is the largest to date describing the relationship between MZ twins and zona procedures, studies with even greater statistical power are needed to clarify it more precisely, particularly in DER and FET settings. A greater overall frequency of MZ twinning for IVF patients may be a function of the higher number of embryos transferred in IVF, rather than discrete zona manipulations. [ABSTRACT FROM AUTHOR]

The commercial availability of highly purified, s.c. administered urinary follicle stimulating hormone (FSH) preparations for ovarian stimulation marked the beginning of a new era in the treatment of infertility. As these new formulations contain essentially no luteinizing hormone (LH), supplemental LH may be needed for optimal folliculogenesis. It was the aim of this pilot study to compare fertilization rates, embryo morphology, implantation rates and pregnancy outcomes prospectively in two age-matched patient groups: women who received highly purified FSH (FSH-HP) (n = 17), and women who received FSH-HP plus recombinant human LH (rhLH, n = 14) throughout ovarian stimulation. All patients received mid-luteal pituitary down-regulation with s.c. gonadotrophin-releasing hormone agonist (GnRHa) (leuprolide). Mean implantation rates were 26.9 and 11.9% in the FSH-HP only and FSH-HP + rhLH groups respectively. The mean clinical pregnancy/initiated cycle rate was 64.7 and 35.7% for the FSH-HP only and FSH-HP + rhLH patients respectively. FSH-HP patients and FSH-HP + rhLH patients achieved clinical pregnancy/transfer rates of 68.8 and 45.5% respectively. One patient in the FSH-HP + rhLH group had a spontaneous abortion; no pregnancy losses occurred in the FSH-HP only group. There were more cancellations for poor ovarian response among FSH-HP + rhLH patients (n = 3) than among FSH-HP patients (n = 1). The trend toward better pregnancy outcomes among patients who received FSH-HP without supplemental rhLH did not reach statistical significance. It is postulated that appropriate endogenous LH concentrations exist despite luteal GnRHa pituitary suppression, thereby obviating the need for supplemental LH administration. [ABSTRACT FROM AUTHOR]

Methods claiming to achieve sex selection by sperm sorting have existed for many years. Numerous applications for safe and effective selection procedures exist in current clinical practice, as sex-linked conditions could be theoretically eliminated by use of appropriate sperm for fertilization or insemination. Use of such techniques could also address the need to effect family balancing for some couples. Modern preconception sex-selection methods may be classified into two general types: those that attempt to segregate spermatozoa on the basis of subtle physical or kinetic features, and those that rely on distinctive nuclear characteristics unique either to X- or Y-chromosome bearing sperm. Laboratories providing sperm sexing using the former method have been available for some years, although the associated efficiency and reproducibility are controversial. Sex selection of spermatozoa by chromatin differences has been shown to achieve significant enrichment of X- or Y-chromosome bearing sperm, but clinical experience in humans is limited. The fundamental elements of the two approaches introduced here are reviewed and compared. Selected key historical concepts in sex selection by sperm sorting are outlined, followed by a summary of promising areas for future research. [ABSTRACT FROM AUTHOR]

With the introduction of intracytoplasmic sperm injection (ICSI), couples with severe male factor infertility have achieved fertilization and clinical pregnancy rates comparable to other in-vitro fertilization (IVF) patients. However, failure of fertilization still occurs in some patients despite the utilization of microsurgical sperm injection techniques. How such fertilization failure after ICSI might impact later ICSI treatment(s) is unknown. In this investigation, couples with complete fertilization failure after ICSI treated from August 1993 to August 1996 were identified (index cycle, n = 21). Additionally, fertilization data from any previous or subsequent infertility treatments were evaluated. Seven patients (33%) had at least one IVF treatment before the index cycle, although no deliveries occurred. Of patients with complete fertilization failure in the index cycle, 48% (n = 10) underwent at least one subsequent ICSI cycle which proceeded to oocyte retrieval. The remainder (n = 11) elected to discontinue treatment. Although six subsequent cycles were cancelled due to poor follicular response (< or = 2 mature oocytes), all patients electing to continue treatment eventually achieved a subsequent embryo transfer. The clinical pregnancy rate per transfer was 45.4% for this group; the delivery and ongoing pregnancy rate per transfer was 36.3%. Review of semen parameters, superovulation characteristics or other clinical parameters during the three study cycles (pre-index, index, and post-index) was not prognostic of fertilization success or reproductive outcomes in later treatments. Fertilization failure with ICSI therefore could not be predicted by prior cycle performance, although total immotility of spermatozoa at time of oocyte retrieval, total teratozoospermia, and low oocyte yield were common characteristics of couples experiencing complete fertilization failure with ICSI. These findings suggest that fertilization failure in one ICSI cycle does not preclude successful fertilization and delivery in a later ICSI treatment. [ABSTRACT FROM AUTHOR]

This investigation describes features of in vitro fertilisation (IVF) patients who never returned to claim their embryos following cryopreservation. Frozen embryo data were reviewed to establish communication patterns between patient and clinic; embryos were considered abandoned when 1) an IVF patient with frozen embryo/s stored at our facility failed to make contact with our clinic for > 2 yrs and 2) the patient could not be located after a multi-modal outreach effort was undertaken. For these patients, telephone numbers had been disconnected and no forwarding address was available. Patient, spouse and emergency family contact/s all escaped detection efforts despite an exhaustive public database search including death records and Internet directory portals. From 3244 IVF cycles completed from 2000 to 2008, > or = 1 embryo was frozen in 1159 cases (35.7%). Those without correspondence for > 2 yrs accounted for 292 (25.2%) patients with frozen embryos; 281 were contacted by methods including registered (signature involving abandoned embryos did not differ substantially from other patients. The goal of having a baby was achieved by 10/11 patients either by spontaneous conception, adoption or IVF. One patient moved away with conception status unconfirmed. The overall rate of embryo abandonment was 11/1159 (< 1%) in this IVF population. Pre-IVF counselling minimises, but does not totally eliminate, the problem of abandoned embryos. As the number of abandoned embryos from IVF accumulates, their fate urgently requires clarification. We propose that clinicians develop a policy consistent with relevant Irish Constitutional provisions to address this medical dilemma.

For fertility patients undergoing in vitro fertilization (IVF), blastocyst culture brings a number of potential advantages over laboratory techniques leading to traditional cleavage-stage embryo transfer. Because day 2-3 embryos normally should transit the oviduct only, their direct exposure to an intrauterine microenvironment is physiologically inappropriate. This mismatch is obviated by blastocyst transfer. Moreover, the nutritional milieu inside the fallopian tube is not the same as within the endometrial compartment, a feature possibly antagonistic to implantation when a day 2-3 embryo is placed directly within the uterus. Delaying transfer to day 5-6 may also improve reproductive outcome by reducing risk of embryo expulsion, given increased myometrial pulsatility measured at day 2-3. However, rigid reliance on a blastocyst culture approach will more often result in treatment cancellation due to embryo loss (no transfer), or having fewer embryos for cryopreservation. The development of sequential media to support embryos in extended in vitro culture was a significant laboratory refinement, since it enabled direct observation of embryos to improve transfer selection bias. This approach, in tandem with blastocyst cryopreservation, leads to fewer embryos being transferred and reducing multiple gestation rate. This review discusses key features of human blastocyst culture and its application in clinical reproductive medicine practice.

Patients with recurrent IVF failure are generally regarded as having a poor prognosis, and when female age exceeds 35 yrs such patients face a particularly bleak outlook. This study reported on blastocyst transfer (BT) performed over a five-year interval in patients seeking "second opinion" after multiple failed IVF cycles. Clinical features and reproductive outcomes were compared between two sets of poor-prognosis IVF patients undergoing BT for the first time, the initial group underwent treatment in 2002 (n=66) and a second group presented five years later (n=392). The two clinical sets had no patients in common. The 2002 group had an average of 3.5 (+/- 1.1) prior failed IVF cycles at baseline, and mean (+/- SD) patient age was 36.4 (+/- 3.9) yrs. Average number of oocytes retrieved in this group was 10.4 (+/- 5.3) with a fertilisation rate of 58.8%. Although embryo arrest resulted in no transfer for 19 patients (28.8%), clinical pregnancy was achieved for 59.6% of transfers. Five years later, 392 patients underwent BT, but this group had an average of 4.5 (+/- 2.3) prior failed IVF cycles. Mean (+/- SD) female age was 36.0 (+/- 3.9) yrs, and the average number of oocytes retrieved in this group was 9.1 (+/- 5.4); the fertilisation rate was 59.5%. No blastocysts were available for transfer in 99 cases (25.3%); clinical pregnancy was achieved for 50.0% of transfers. The number of blastocysts transferred was similar in the two groups (1.6 vs. 1.3; p=0.06); the twinning rate rose slightly from 8.2% to 15.1% (p=0.12) despite an increased utilisation of single embryo transfer in 2007 (19.7% vs. 22.2%; p=0.40). Comparisons from 2002 and 2007 found no important differences between the two patient groups, except for a significantly higher rate of prior failed cycles in the 2007 group (p<0.001). This refractoriness was accompanied by a somewhat reduced blastocyst cryopreservation rate in 2007, compared to 2002 (27.6% vs. 29.5%; p=0.44). Clinical pregnancy rates are not adversely affected by application of BT in patients with multiple prior unsuccessful IVF cycles. For these patients, our data suggest that extended embryo culture and BT should be considered. Further controlled studies are needed to document more precisely the role of BT in this sub-set of refractory IVF patients.

In this report, our early experience with screening, monitoring and coordinating IVF utilising gestational carrier treatment is described. Although congenital and iatrogenic etiologies for uterine factor infertility manifest distinctly different reasons for considering a gestational carrier approach, we outline a unified management strategy for both conditions. One patient had congenital absence of the uterus and proximal vagina (Mayer-Rokitansky-Kuster-Hauser syndrome variant), while another patient presented post-hysterectomy and adjuvant brachytherapy for invasive squamous cervical carcinoma. Conception was established for both patients, the first pregnancies to be achieved using an IVF/gestational carrier technique in Ireland. As demonstrated here, selected patients with at least one intact ovary who suffer from uterine factor infertility can be excellent candidates for IVF with embryo transfer to a carefully screened gestational carrier. The role of individual and group counselling is reviewed; professional legal advice is prudent in complex cases.

Objective: To evaluate standardized process of care data collected on selected hospitals serving a remote, rural section of westernmost North Carolina., Materials & Methods: Centers for Medicare & Medicaid Services (CMS) data were retrospectively analyzed for 21 clinical parameters at Fannin Regional Hospital (FRH), Murphy Medical Center (MMC), and Union General Hospital (UGH). A binomial test was used to compare each study site to state (NC) and national (U.S.A.) average., Results: Summary data showed FRH to have higher scores on a significant number of standardized clinical process of care measures compared to state (p < 0.05) and national (p < 0.005) averages. Too few process of care measures at UGH were significantly higher than state and national averages to conclude that differences were not due to Type I error. Similarly, at MMC too few process of care measures were significantly higher than national averages to conclude that observed differences were not attributable to Type I error. MMC did not achieve a significantly higher score on any process of care measure when compared to state averages., Conclusion: Despite limitations associated with summary data analysis, the CMS "Hospitals Compare" information suggests that process of care scores at FRH are significantly higher than the state and national average. As these hospital quality data are freely available to patients, it remains to be determined what impact this may have on hospital volume and/or market share in this region. Additional research is planned to identify process of care trends in this geographical area.

Purpose: To compare selected characteristics in two North Carolina counties to document women's health services at the geographical extremes of the state., Methods: Using aggregated 2004 data obtained from the North Carolina State Center for Health Statistics, obstetric and perinatal characteristics were experimentally analyzed for the westernmost and easternmost counties in North Carolina (Cherokee and Dare County, respectively)., Findings: During the experiment period, 489 infants were delivered in Dare County (population 33,518), while 259 births were recorded in Cherokee County (population 25,289). Prenatal care was established by most women in both counties by the second gestational month. Women in Cherokee County were younger and less educated at delivery than women in Dare County, and smoking prevalence was higher in Cherokee County than in Dare County (31.3% vs 12.9%; p <0.01). Cherokee County infants required assisted ventilation and other medical interventions more often than babies born in Dare County (p <0.01) yet significantly fewer cesarean deliveries were performed in Cherokee County than Dare County (25.5% vs 35.2%; p = 0.04)., Conclusion: This pilot study showed a significantly higher rate of tobacco use, and lower maternal education level in Cherokee County was associated with a higher incidence of multiple maternal complications and neonatal interventions compared to Dare County. Interestingly, the cesarean delivery rate was lower in Cherokee County despite these factors. We found < 10% of babies born in the study regions required any neonatal intervention. Early and almost universal access to prenatal care did not appear to be a problem at either site. Our preliminary comparison identified important limitations in this government-sponsored dataset that rendered logistic regression analysis methodologically impossible. Changes in process could improve surveillance based on patient-level data and facilitate multivariate analysis. Specific interventions to optimize women's health services form the basis of future experimental research, including larger regional populations.

The frequency of triplet gestation is low in humans, estimated at 1:6400 deliveries. Monochorionic gestations represent a subpopulation of approximately 10% of these triplet pregnancies. Hypertensive complications are known to occur with greater frequency in the context of multiple gestation. In this report we describe microscopic placental changes associated with pre-eclampsia and proteinuria in the setting of an uncommon monochorionic-triamniotic triplet pregnancy achieved via in vitro fertilization. Histologic features observed in this case include placental stromal fibrosis and increased syncytial nodularity (Tenney-Parker change). In this triplet delivery resulting from two consecutive fissions of a single embryo, chorion and amnion configuration are also characterized with a review of the literature discussing the potential relationship between in vitro culture conditions and monozygotic multiple gestation.

The medical and psychological treatment for a 37-year-old Caucasian G6 P1051 woman who presented for evaluation of secondary infertility and recurrent pregnancy loss is described. Although one living child had been conceived without medical assistance, that delivery preceded the present evaluation by ten years and involved a different partner. With the current husband, the patient had two miscarriages and a left ectopic pregnancy. The couple had attempted controlled ovarian hyperstimulation and in vitro fertilization (IVF) elsewhere, but the cycle was cancelled due to poor follicular response. About one year before consultation at our institution, the couple established a pregnancy although the infant was born at 24 weeks with a cardiac anomaly, living only 40 days. Additionally, a persistent cervical lesion required cone biopsy before any fertility treatment could resume. Andrology evaluation found the husband's sperm DNA fragmentation index to be 48.6%. This constellation of stressors represented substantial emotional issues and psychological therapy/counseling was recommended. After obtaining psychological clearance, the couple underwent IVF and 16 oocytes were retrieved. Four embryos were transferred, and a healthy male infant was delivered at term. Although multifactorial infertility can be associated with very poor reproductive outcomes, the advanced reproductive technologies merit consideration during management of complex clinical challenges. Standard IVF strategies can be optimized by inclusion of thorough psychological assessment and counseling.

While human oocytes have been successfully cryopreserved using traditional slow-rate freezing protocols, inconsistent results post-thaw have limited the routine clinical application of oocyte cryopreservation. Despite interest in the potential benefits of vitrification as an alternative laboratory approach to long-term oocyte preservation in assisted reproduction, there is little agreement on how best to configure such cryopreservation protocols to optimize oocyte viability. To comparepost-thaw oocyte survival rates,we performed cryoloop vitrification of human oocytes utilizing two different cryoprotectant mixtures that included polymer macromolecules. Human oocytes (n = 1120) were obtained from consenting patients undergoing in vitro fertilization, but only failed-matured (uninseminated) or failed-fertilized (inseminated but without 2pn development) were included in this investigation. Protocol A consisted of 20% ethylene glycol and 20% dimethyl sulphoxide + 0.4 M sucrose and 20% synthetic serum substitute. Protocol B consisted of 20% ethylene glycol and 20% dimethyl sulphoxide + 0.65 M sucrose, 1 mg/ml polyethylene glycol, 10 mg/ml Ficoll and 20% synthetic serum substitute. Following cryostorage for 10-14 d at -196 degrees C, the survival rate for oocytes vitrified with protocol A was 80.9%, whereas the post-thaw viability among protocol B oocytes was 80.6% (p > 0.005). Our results indicate that an ethylene glycol + dimethyl sulphoxide mixture (with or without polymer macromolecules) can be an effective cryoprotectant strategy for human oocyte vitrification; either approach can be employed without any observed compromise in post-warming survival and/or morphology.

Conjoined twins represent the most uncommon twinning mechanism in humans, with an incidence approaching 1:100,000 deliveries. Although several conjoined male twins have occasionally been reported, for unexplained reasons most cases of conjoined twins are female. Of all the female conjoined twin sets either documented by medical authorities or referenced in ancient literary sources, in only one case were pregnancy and delivery successfully achieved by the conjoined twins themselves. We describe the highly unusual circumstance of the Blazek sisters, an extreme developmental example of the terminal monogenital pygopagus type of conjoined twins in which one of the joined sisters conceived and underwent labor and childbirth. Although little information is known about their own birth, these conjoined twins paradoxically hold a unique place in the history of obstetrics. Information from formal anatomic examinations of the sisters and their exploitative circus exhibitions is outlined with a view to explain relevant reproductive events. We present the sensational conception, pregnancy course, and subsequent vaginal delivery of a healthy male infant as summarized from contemporary sources. Additionally, the significance of pygopagus twins is discussed with regard to other types of monozygous twinning. Although modern operative techniques have been a welcome advance in the science of conjoined twin separation, the Blazek case is another reminder that, even in the era before complex surgery, conjoined twins were not necessarily consigned to an incomplete reproductive career.

Etanercept (Enbrel; Wyeth-Ayerst/Immunex Inc, Seattle, WA, USA) is a subcutaneously administered novel fusion protein consisting of the extracellular ligand-binding domain of the 75 kD receptor for tumor necrosis factor-alpha (anti-TNFalpha) and the Fc portion of human IgG1. The agent is synthesized by plasmid transfection of a Chinese hamster ovary cell line, utilizing recombinant DNA technology. Etanercept was approved by the US FDA for treatment of multi-drug resistant rheumatoid arthritis in 1998, but no human data exist regarding the impact of anti-TNFalpha therapy on human reproductive function or its use before ovulation induction. As TNFalpha potentiates collagenolysis via matrix metalloproteinase gene expression (thereby facilitating ovulation), there exists a theoretical risk that TNFalpha-inhibition could exert an undesirable effect on ovulation and pregnancy. In this report, we describe the first case of ovulation induction, intrauterine insemination, normal pregnancy and singleton delivery of a healthy infant following chronic ( > 1 year) pre-ovulatory TNFalpha-inhibitor therapy for rheumatoid arthritis. Reproductive endocrinologists and obstetrician-gynecologists should be familiar with etanercept therapy in the context of severe rheumatic disease, and offer appropriate reassurance regarding its safe use for infertility patients planning ovulation induction.

The molecular biology of human cloning and aging research depend on the closely related laboratory techniques supported by a thorough understanding of cell-signaling processes. Unfortunately, the link between these two research fields has received only marginal attention in the lay press. Cloning is possible when somatic cell differentiation is successfully reprogrammed, and clinical control of cellular senescence depends on a proper reconfiguration of the predetermined number of divisions permitted during the cell life-cycle (the so-called "Hayflick Limit"). In this paper, we discuss these two concepts and compare the impact likely to be associated with bioengineering studies that facilitate both human cloning and longevity therapy.

Objective: To describe serum levels of human chorionic gonadotropin (hCG) as a function of hCG injection method (subcutaneous vs. intramuscular) among infertile women undergoing ovulation induction., Design: Prospective, randomized clinical trial., Setting: Major urban infertility referral center., Patient(s): Women presenting for infertility evaluation and ovulation induction., Intervention(s): Controlled ovarian hyperstimulation was followed by 5,000 IU urinary (nonrecombinant) hCG injection, given intramuscularly (i.m.) or subcutaneously (s.c.)., Main Outcome Measure(s): Serum hCG levels measured 24 hours after administration of hCG, and patient tolerability of injected hCG., Result(s): There were no statistically significant differences in age or body mass index (BMI) among patients receiving hCG s.c. (n = 13) or i.m. (n = 15). Mean [IQR (25; 75)] serum hCG levels in the s.c. and i.m. groups were 171.7 [27.0; 207.0] and 142.2 [102.5; 157.5] mIU/mL, respectively. No adverse events were registered by any patient receiving hCG by either injection method. In this non-IVF population, two pregnancies were established in each subgroup (4 of 28, or approximately 14% pregnancy rate)., Conclusion(s): The s.c. administration of 5,000 IU hCG (reconstituted in vol. = 0.5 mL) was well tolerated by all women in this study and was associated with postinjection serum hCG levels similar to those observed after administration of an equivalent i.m. hCG dose. This investigation suggests that clinical use of s.c. hCG is suitable for lean women (e.g., BMI <30) undergoing ovulation induction, but additional data are needed to study the appropriateness of s.c. hCG administration in heavier patients.

Objective: To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic-appearing ovaries in an infertility setting., Methods: Among women referred for infertility evaluation (n = 54), homocysteine, androstenedione, DHEAS, total testosterone, fasting insulin/glucose and methyltetrahydrofolate reductase (MTHFR) polymorphism status (C677T mutation) were studied. Ovaries were examined via transvaginal sonogram by one observer and scored as either normal (n = 18) or polycystic (n = 36)., Results: When polycystic ovaries were identified, mean total testosterone was significantly higher than when non-polycystic ovaries were present (p = 0.01), although no measured androgen was outside the normal reference range in either group. Average BMI was higher in the polycystic group, but the difference was not significant (p = 0.10). We observed a trend toward higher mean fasting insulin levels in women with polycystic ovaries, but this increase did not reach statistical significance (p = 0.07). Median plasma homocysteine was identical (7.0 mmol/l) in both populations, and no study subject exceeded the current recommended maximum reference value., Conclusions: In this population, the presence of polycystic ovaries was associated with higher serum androgens (especially total testosterone) although none of the measured androgens were above the normal range. While fasting insulin levels were also higher in this group, median plasma homocysteine levels were similar irrespective of ovarian morphology. Concomitant plasma homocysteine derangements in this population of young, lean patients with polycystic-appearing ovaries seem unlikely. Further studies are needed to clarify the role(s) of homocysteine in human reproductive physiology.

This report presents the development of endometrial adenocarcinoma after diagnosis of polycystic ovary syndrome (PCOS) in three premenopausal women. Such cases illustrate the increased potential for endometrial hyperplasia and malignancy in the setting of chronic anovulation associated with PCOS and underscore the need for prompt identification and treatment. Attention to endometrial thickness (as measured by transvaginal sonogram) and elevated insulin level (as measured by fasting plasma insulin) can improve clinical surveillance of both conditions and preserve reproductive potential for women with PCOS.

That the zona pellucida (ZP) plays a prominent role in the physiology of some human twinning is an attractive, albeit incompletely proven, medical hypothesis. Indeed, an association has been proposed between manipulation of the ZP and/or native ZP microarchitecture and monozygotic (MZ) twins. Ovulation induction also has been theoretically linked to in vivo ZP alterations facilitating MZ twin development. In vitro fertilization (IVF) relies on necessary (and, in some cases extended) embryo culture techniques potentially creating subtle ZP changes and subsequent MZ twinning. With growing experience in the assisted reproductive technologies and particularly IVF, some preliminary reports have noted an increased frequency of MZ twins after procedures that artificially breach the ZP (i.e., intracytoplasmic sperm injection [ICSI], or 'assisted hatching'). Such ZP manipulations ostensibly enhance oocyte fertilization or facilitate blastocyst hatching, thus improving pregnancy rates for couples undergoing fertility treatment. Evidence exists both to challenge and support the connection between these phenomena and MZ twins. This report outlines the fundamental embryological processes believed responsible for these conflicting observations; the current literature on the subject of human ZP micro-manipulation and MZ twins is also discussed.

We describe the longest-known continuous use of clomiphene citrate ever reported in a human. As a result of a pharmacy error, a woman took 50 mg/day clomiphene citrate for three months. The prolonged use of this medication resulted in ovarian hyperstimulation and unilateral oophorectomy for torsion.

Polycystic ovary syndrome (PCOS) describes a convergence of chronic multisystem endocrine derangements, including irregular menses, hirsutism, obesity, hyperlipidemia, androgenization, large and cystic-appearing ovaries, insulin resistance and subfertility. Few PCOS patients exhibit all of these features, and often only one sign or symptom is evident. The sequelae of PCOS reach beyond reproductive health, as women affected with PCOS have increased relative risks for myocardial infarction, hypertension, ischemic heart disease, thromboembolic disease and diabetes. Although the adverse health consequences associated with PCOS are substantial, unfortunately most women are not aware of these risks. Indeed, in infertility practice such concerns are secondary as most patients are referred for treatment specifically to achieve a pregnancy. Impairments in insulin metabolism appear central to the physiologic cascade of PCOS, yet clomiphene therapy fails to remedy this defect. Several investigators have described satisfactory reproductive outcomes for PCOS patients treated with oral insulin-lowering agents. In this report, we outline a diagnostic and therapeutic approach for women with PCOS refractory to clomiphene with attention to the underlying insulin imbalance associated with impaired fertility.

"Ovarian reserve" describes the native oocyte endowment and is closely associated with reproductive potential. As a diagnostic entity, ovarian reserve screening developed from clinical experience with the advanced reproductive technologies--particularly in vitro fertilization. Diminished ovarian reserve generally presages a poor response to any fertility treatment, and sharply limits the possibility of successful pregnancy. Screening for ovarian reserve is a fundamental component of the initial infertility evaluation, since it is a key determinant of what, if any, treatment should be offered. Methods of clinical ascertainment of ovarian reserve may be classified in two groups: passive and provocative testing. Both approaches seek to provide information regarding oocyte quality and quantity, which then may be used to direct specific therapeutic interventions. This monograph presents basic elements of ovarian reserve testing as currently practiced, and provides insights into the interpretation and limitations of these assessments.

Purpose: Our purpose was to determine if the presence of a hydrosalpinx effects the outcome of in vitro fertilization (IVF)-embryo transfer., Methods: We performed a retrospective analysis of IVF cycle stimulation sheets., Results: A total of 1000 patients with tubal factor infertility was analyzed. There were 60 hydrosalpinx patients who underwent 116 initiated cycles with 106 embryo transfers, compared to 940 control patients undergoing 1428 initiated cycles with 1150 embryo transfers. Both groups had a similar response to ovarian stimulation, number of oocytes retrieved, and number of embryos transferred. The hydrosalpinx group had a significantly higher preclinical loss rate (22/59 = 37% vs 80/566 = 14%; P = 0.001), a significantly lower implantation rate (55/352 = 16% vs 795/3795 = 21%; P = 0.013), a trend toward a reduced delivery rate per transfer (28/106 = 26% vs 387/1150 = 34%; P = 0.066), a significantly higher ectopic pregnancy rate (5/59 = 8% vs 16/566 = 3%; P = 0.04), and a similar spontaneous abortion rate (9/37 = 24% vs 99/486 = 20%; P = 0.28) compared to the control tubal factor group., Conclusions: This study demonstrates a decrease in implantation rates and an increase in preclinical miscarriages and ectopic pregnancies in patients with hydrosalpinges compared to tubal-factor patients without sonographic evidence of dilated fallopian tubes.

While the fertilising spermatozoon supplies the active centre directing the human zygote's first mitotic division, the relative contributions of the sperm head and tail (as well as the importance of the sperm's general structural integrity) to subsequent developmental processes remain incompletely studied. The sperm nucleus contains paternal chromatin necessary for restoration of a diploid genome, but the functional role of the sperm tail (either attached or dissected) in early human embryonic growth is not known. In this investigation using oocytes donated by in vitro fertilisation patients, human oocytes were injected with isolated sperm heads (n = 73), isolated sperm flagella (n = 11) or both (dissected sperm heads + free sperm tails, n = 26). The formation of bipronucleate zygotes was recorded for each method. Among oocytes surviving injection with isolated sperm heads, 44 of 66 (67%) formed two pronuclei. Of oocytes receiving only sperm tails, 2 of 11 (18%) displayed two pronuclei, but a single polar body was evident in both cases. When dissected spermatozoa parts (head + tail) were jointly injected, 12 of 26 (46%) developed two pronuclei. From embryos resulting from each of these three fertilisation regimes, blastomere biopsies were obtained and subjected to multiprobe fluorescent in situ hybridisation (FISH) analysis to detect mosaicism or aneuploidy arising from these experimental treatments. Only embryos with growth sufficient to permit sampling of at least two blastomeres were evaluated, and FISH analysis was successful in 25 of 29 (86%) embryos tested. Of 12 embryos derived from injection of an isolated sperm head, only one was normal diploid; the remaining 11 were mosaic. Both embryos resulting from injection of an unattached sperm tail were mosaic. Of 11 embryos generated from oocyte injection with sperm head + tail segments, 10 (91%) were mosaic and only one was normal diploid. Results from this study show that injection of isolated sperm segments can permit oocyte activation and bipronuclear formation. However, a high rate of mosaicism in human embryos originating from disrupted sperm or sperm components suggests that more than a 'sum of parts' is needed for later development. The structural integrity of the intact fertilising spermatozoon appears to contribute to normal human early embryogenesis.

The centrosome is an organelle essential to proper chromosomal migration and normal cell growth. In the human, the centrosome is comprised of two centrioles and the pericentriolar cytosol; its control of embryo cleavage processes derives from its role as a locus for spindle organisation. At fertilisation, it is the human sperm centrosome that is responsible for ordering these processes, as the oocyte appears not to contain working centrosomal structures. Abnormalities in fertilisation or early embryo cleavage could be related to impaired sperm centrosome structure or function in some cases. While potential future treatments of infertility due to a defective centrosome could involve use of a donor centrosome to restore normal cell development, such an approach would depend on accurate localisation of this organelle for subsequent transplantation. To locate centrosomal components in the heads and tails of human spermatozoa, labeling was performed on intact spermatozoa using antibodies of known specificity to highly-conserved centrosomal elements. Following general mapping of immunofluorescent signals, unlabeled sperm were dissected to form head/tail sperm fragments which were then separately tested. Distribution of centrosomal proteins in head and tail fragments was assayed for each separation method. Three reagents were compared: 1) rabbit anti-mitotic spindle protein (anti-MSP) antibody, 2) rabbit polyclonal centriole-specific antibodies, and 3) mouse monoclonal anti-MPM-2 (a centrosome phospoprotein) antibody. Of these, anti-MPM-2 antibody appeared to be the most reliable, labeling centrosomal elements in 63% (n = 1,386) of treated spermatozoa. Sequential utilization of n-butylamine to effect head/tail separation followed by anti-MPM-2 antibody labeling was a satisfactory method of centrosome localisation. Microextraction of centrosomes and pericentriolar matrix identified by this method awaits further testing.

To describe practice trends for total abdominal hysterectomy (TAH) and supracervical abdominal hysterectomy (SCH) in New York State and to identify fiscal features associated with these two operations, all inpatient discharges for TAH and SCH performed for benign indications from 1990 to 1996 were reviewed using the Statewide Planning and Resource Cooperative System, a centralized data reporting system. For each year examined, the number of TAHs and SCHs performed, the procedure rates adjusted for the total New York State female population, and the per diem charge (calculated from mean institutional charge as a function of average length of stay) were evaluated. While the TAH rate declined in New York State, from 34.0 in 1990 to 28.4 in 1996 (P = .01), the SCH rate increased nearly five-fold during the same period, from 0.62 to 3.07 (P = .0003). Patients tended to be discharged later following SCH than for TAH, although by 1996, the LOS for both operations was equivalent. The per diem institutional charge for SCH was consistently higher than for TAH in each year studied. The changes in charge and relative frequency of TAH and SCH in New York State invite further study to describe these trends more fully.

Objective: To describe nationwide practice trends for two principal techniques of abdominal hysterectomy in the United States, numbers and rates of total (TAH) and supracervical (SCH) hysterectomy were reviewed with charges for each operation., Methods: Practice patterns for all inpatient TAH and SCH discharges in the US from 1991 to 1994 were studied using HCUP-3 NIS, a nationwide hospital discharge database. Hysterectomies performed for malignant disease, vaginally or with laparoscopic assistance were not sampled. For each year studied, the number and rate of TAH and SCH, average length of stay (LOS), and mean institutional charge were evaluated., Results: From 1991 to 1994, the US TAH rate (cases/10000 females) decreased significantly from 25.7 to 20.5 (P = 0.02). During the same interval the SCH rate increased significantly from 0.16 to 0.41 (P = 0.04). Nevertheless, TAH accounted for > 99% of all abdominal hysterectomies for each of the 4 years evaluated. The mean institutional charges for the two operations generally depicted SCH to be more costly than TAH., Conclusion: The national rates of TAH and SCH rates changed significantly in the United States from 1991 to 1994, with TAH declining and SCH increasing. This mix of cases continues to reflect a strong preference for TAH. Although hospital charges for both procedures increased during this study, these data show that SCH is more expensive than TAH. The much lower utilization of SCH renders nominal its impact on national healthcare expenditures, however. Further studies are needed to assess specific causative factors for these changes in US hysterectomy technique.

Problem: Restricted expression of H-Y antigen on Y-chromosome-bearing sperm has been reported in some species, although such preferential expression for H-Y antigen in human sperm has yet to be described. In this study, an immunomagnetic approach was used to characterize antigen expression patterns as a function of sex-chromosome content., Method of Study: Human sperm was treated with monoclonal immunoglobulin (Ig) M antibodies directed against H-Y antigen. This preparation then was incubated with sheep antimouse IgM antibody affixed to paramagnetic beads, which then were exposed to a magnetic field and sorted. X- and Y-chromosome frequencies in the two subgroups of sperm were assayed by multiprobe fluorescent in situ hybridization (FISH)., Results: Sperm were immunomagnetically separated into two populations: a reactive group (presumably, H-Y Ag+); and a nonreactive group (presumably, H-Y Ag-). Triple-color FISH analysis of 1,600 spermatozoa (800 in each group) showed the antigen's expression to be somewhat more prevalent among Y-chromosome-bearing sperm (54.1%), but a large proportion of Y-chromosome-bearing sperm (49.0%) did not express this antigen. The difference was not significant (P = 0.43)., Conclusions: The expression of H-Y antigen has a slightly higher frequency in human sperm containing the Y-chromosome, but its expression among X-chromosome-bearing sperm also is considerable. Current immunologic techniques relying on this antigen are unlikely to effect the sex selection of human sperm.

Objective: To compare the endocrine responses of patients who first received hMG plus FSH, then were treated in a subsequent cycle with FSH alone., Design: Retrospective study., Setting: An academic research environment., Patient(s): Ninety-six women with pituitary down-regulation who underwent two sequential IVF treatments, the first with combined hMG and FSH and the second with FSH alone., Main Outcome Measure(s): Duration of stimulation, serum estradiol level on the day of hCG administration, amount of gonadotropin used, number of oocytes retrieved, number of oocytes fertilized, and selected preembryo morphologic features., Result(s): No difference in the mean duration of stimulation was observed between the treatment cycles among patients who received hMG and FSH (11.9 days) followed by FSH alone (11.7 days). The mean number of oocytes retrieved, the mean number of oocytes fertilized, the percentage of preembryo fragmentation, and the preembryo cell number at transfer did not differ significantly between the stimulation protocols. The cumulative amount of gonadotropin used during stimulation was slightly greater in the cycles stimulated with FSH alone, but this difference was not significant (29.4 ampules of hMG plus FSH versus 31.8 ampules of FSH alone). Serum estradiol levels measured on the day of hCG administration during stimulation with hMG and FSH (1,382 pg/mL) were higher than those measured during stimulation with FSH alone (1,149 pg/mL)., Conclusion(s): Follicular response and preembryo quality were not significantly different when patients were treated first with hMG and FSH and then with FSH alone in a subsequent cycle. Similarities in ovarian response and preembryo characteristics, as well as differences in estradiol patterns seen in each stimulation setting, should be anticipated when patients receive these protocols.

Objective: To present a review of our experience and that of the medical literature in the diagnosis and management of oral pregnancy tumor (pyogenic granuloma), the natural History of the disease, its hormonal etiology, histopathologic features and management strategies., Study Design: Medical literature review., Results: This common, benign, hyperplastic oral mucosal lesion is much less familiar to gynecologists and obstetricians than to dentists., Conclusion: For practitioners engaged in primary care obstetrics and gynecology, routine oral examination and proper identification of pyogenic granuloma are important to avoid misdiagnosis and overtreatment.