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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]

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.

Objective: To describe a previously unreported adnexal defect as a cause of an abnormal hysterosalpingogram (HSG), identified during infertility evaluation., Material and Method: An abnormal hysterosalpingogram (HSG) consistent with partial left tubal obstruction or hydrosalpynx was identified during the evaluation of a 33 year-old nulligravida with no prior surgical history. At laparoscopy, the diagnosis was revised when a approximately 3x4cm regular, ovoid, physiologic aperture was noted in the central aspect of the left broad ligament in the region corresponding to the HSG defect. The lesion was explored but not repaired. Bilateral tubal patency was confirmed via indigo carmine chromopertubation., Results: Ovulation induction and intrauterine insemination were undertaken based on findings at surgery and careful discussion of same with the couple. The patient successfully conceived and had a normal term delivery., Conclusion: While HSG abnormalities discovered during infertility assessment are not unusual, intrinsic or de novo peritoneal defects have not been described previously. Abnormal radiographic findings may be explained by this lesion in selected cases.