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There are few treatments for patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Women with RPL and unexplained infertility have lower T regulatory cell (T(reg)) expression when compared to fertile controls. A murine model has been developed with depletion of regulatory T cells (DEREG) after administration of diphtheria toxin (DT), resulting in smaller litter sizes, secondary to embryo implantation failure. Numerous murine studies have shown that adoptive transfer of CD4(+)CD25(+)FoxP3(+) T(regs) from donors improves litter sizes in DEREG mice with depleted T(regs). Our hypothesis is that DEREG mice treated with a single dose of DT will deplete T(regs) and subsequently decrease litter sizes and that treatment with rapamycin (sirolimus; Pfizer) during the time of embryo implantation will increase T(regs) and restore litter sizes nearly back to normal levels. Syngeneic mating of DEREG mice after depletion of T(regs) resulted in smaller litter sizes and this defect was reversed when these DEREG mice were treated with rapamycin at the time of embryo implantation. The importance of T(regs) at the time of embryo implantation has been well established and immunotherapy treatments, such as rapamycin (mammalian target of rapamycin inhibitor), may prove to be an effective treatment for patients with RPL, RIF, or unexplained infertility with low T(reg).

PURPOSE: To describe controlled ovarian stimulation (COS) in a population of women with GATA2 deficiency, a genetic bone marrow failure syndrome, prior to allogeneic hematopoietic stem cell transplant METHODS: This is a retrospective case series of nine women with GATA2 deficiency who underwent oocyte preservation at a research institution. Main outcomes measured include baseline fertility characteristics ((antimullerian hormone (AMH) and day 3 follicle-stimulating hormone (FSH) and estradiol (E2)) and total doses of FSH and human menopausal gonadotropins (HMG), E2 on day of trigger, and total number of metaphase II oocytes retrieved. RESULTS: The mean age was 24 years [16–32], mean AMH was 5.2 ng/mL [0.7–10], and day 3 mean FSH was 5.1 U/L [0.7–8.1], and E2 was 31.5 pg/mL [

In vitro fertilization (IVF) is the perfect example of translational research. Changes in IVF and the IVF laboratory have been transmitted to clinical care, showing dramatic improvements in health outcomes, including notable increases in the cumulative pregnancy rate. Current research in the laboratory focusing on culture media, embryo selection criteria, and implementation of genetic testing and manipulation promises to translate to further improvements in our ability to assist human reproduction. The field of IVF and ART remains a large source for clinical and scientific discovery and development, and will require the proper interested and invested personnel, occupational structuring, and funding for continued success.

Prior studies have validated the ability of the SART embryo scoring system to correlate with outcomes in cleavage stage embryo transfers. However, this scoring system has not been evaluated in blastocyst transfers. The objective of this study was to estimate the correlation between the simplified SART embryo scoring system and ART cycle outcomes in single blastocyst transfers.All fresh, autologous single blastocyst transfers cycles from a large ART center from 2010 were analyzed. Blastocysts were given a single grade of good, fair, or poor based upon SART criteria which combines the grading of the inner cell mass and trophectoderm. Multiple logistic regression assessed the predictive value of the SART grade on embryo implantation and live birth.Seven hundred seventeen fresh, autologous single blastocyst transfers cycles were included in the analysis. The live birth rate was 52 % and included both elective and non-elective SBT. Chi square analysis showed higher live birth in good grade embryos as compared to fair (p=0.03) and poor (p=0.02). Univariate binary logistic regression analysis demonstrated SART embryo grading to be significantly correlated with both implantation and live birth (p0.01). This significance persisted when patient age, BMI, and the stage of the blastocyst were controlled for with multiple logistic regression. In five patients with a poor blastocyst score, there were no live births.These data demonstrate that the SART embryo scoring system is highly correlated to implantation and live birth in single blastocyst transfers. Patients with a good grade embryo are excellent candidates for a single blastocyst transfer.

One hundred six women suffering from obstructive tubal disease not corrected by previous surgery were treated in an in vitro fertilization (IVF) program. Ovulation was induced by 3 amps of human menopausal gonadotropin (HMG)/day starting on the third day of the cycle for 5 days. In most of the patients the regimen was continued for another 1-3 days, depending on the individual's ovarian response (mean, 20 +/- 5 amps/cycle). Monitoring consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin (HCG), 10,000 IU, was administered when more than two large (1.5 to 1.8 cm in diameter) follicles were visualized. Using this regimen, a mean of five follicles per woman was aspirated, from which a mean of 3.9 ova was recovered. The oocytes were pre-incubated for 8 or 24 hr, according to the morphological degree of mucification and dispersal of the oocyte-corona-cumulus complex. Following exposure to washed spermatozoa for 16 hr, a 68% fertilization rate was obtained. Oocytes were transferred into the uterus 48 hr after laparoscopy. Ninety-nine transfers (93% of the women) of 1-8 embryos (mean, 2.9/woman) were performed and resulted in 16 clinical pregnancies. No pregnancies occurred in 14 women transferred with one to three oocytes in the pronuclear stage and only one pregnancy (7.1%) was obtained in 14 women transferred with one cleaved oocyte. Over 70% of the women were transferred with two or more cleaved oocytes: in this group the pregnancy/transfer rate was 21%. Of the pregnant women 5 of 16 (31%) aborted between 6 and 10 weeks of gestation and 1 (6%) had an ectopic pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Seventy-one oocyte-corona-cumulus complexes (OCCCs) were obtained from eight women who conceived and delivered following in vitro fertilization (IVF) and eight women who were matched for the number of embryos transferred into the uterus but failed to conceive following the procedure. The steroid secretion of these OCCCs was assessed during a 24-hr culture period. Intermediate (N=35) and mature (N=36) complexes did not differ in steroid secretion, and progesterone was the major steroid secreted. OCCCs associated with a fertilized oocyte (N=59) produced significantly (P

The likelihood of establishment of a term pregnancy from in vitro fertilization (IVF) is related to the estradiol (E2) pattern and peak level. To examine the influence of super high E2 peak levels (>-2000 pg/ml), we reviewed the clinical outcomes of all IVF cycles with follicular phase E2 levels >2000 pg/ml from May 1982 through June 1987. Among 1651 IVF cycles initiated during this time, 102 cycles (6.2%) had super high E2 levels. Twenty-seven of these cycles occurred in 34 IVF attempts in 12 women. Stimulation was performed with human menopausal gonadotropin (hMG) in 96 cycles and follicle-stimulating hormone (FSH) in 6 cycles. A mean of 9.3±0.7 oocytes per cycle was recovered, of which 5.5±0.5 fertilized and underwent cleavage. In 11 cycles, with a mean of 6.8 oocytes recovered, none fertilized. Polyploid fertilization occurred in 23 of 90 cycles (25.6%), and 40 of 558 fertilized oocytes (7.2%). From these cycles, 10 clinical pregnancies (9.8%) have resulted: 6 pregnancies in 59 cycles with luteal-phase progesterone support (10.2%) and 4 pregnancies in 31 cycles without luteal-phase progesterone support (12.9%). Among the 1549 cycles with peak E2 levels

There is currently a controversy as to whether the prolonged in vitro culturing of embryos before freezing has a deleterious effect on their ability to survive freezing and thawing. We compared the survival rate of frozen/thawed mouse embryos after in vitro culturing, from the two-cell stage through the eight-cell, morula, and blastocyst stages, with the survival of embryos developed in vivo to the same stages. Following induced superovulation and mating, embryos in the desired cleavage stage were flushed from the oviducts and/or uterus and either cultured in vitro or frozen immediately in sterile glass ampoules to -40 degrees C and plunged into liquid nitrogen for storage. Dimethyl sulfoxide (1.5 M) was used as cryoprotectant. After thawing, the survival rate (determined by the morphological appearance of the embryos) was significantly lower in the eight-cell stage embryos in the group grown in vivo (P less than 0.05). The number of embryos developing into expanded and hatched blastocysts was not significantly different when the in vivo vs in vitro cultures were compared over each of the three cleavage stages: eight cells (82 vs 83%), morula (92 vs 87%), and blastocyst (33 vs 51%), respectively. There was a significant decrease in the development rate of blastocyst-stage embryos when compared with earlier stages under both culture conditions (P less than 0.001). It is concluded that, compared to in vivo-grown embryos frozen at the same stages, prolonged in vitro culture does not reduce the embryos' ability to develop normally.

The study of immunologic factors in infertility is in its infancy, and many questions remain to be answered. Further studies using newer techniques are needed to elucidate the actual contributions of immune mechanisms to infertility. Understanding the role of immunologic factors should lead to more effective treatment of patients whose infertility is immunologic in etiology.

The effect of hyaluronidase removal of the cumulus oophorus on the in vitro fertilization rate of oocytes obtained from patients with poor oocyte fertilizability has been evaluated. Eighty-eight oocytes were obtained from 13 patients undergoing in vitro fertilization and embryo transfer (IVF-ET) for indications of male-factor, immunological, and idiopathic infertility. In addition, patients in whom fertilization did not occur on previous IVF cycles were evaluated in the study. The oocytes of each individual patient were randomly assigned into a treatment (removal of the cumulus; N = 40 oocytes) or nontreatment group (control; N = 48 oocytes). Hyaluronidase was used to remove the cumulus immediately following oocyte retrieval, and insemination was performed 6-8 hr later. The overall oocyte fertilization rate (both treated and untreated) was 42%. The treatment group demonstrated a higher rate of fertilization compared to the nontreatment group (55% vs 31%; P less than 0.05). Examination of various patient groups revealed a statistically significant difference in fertilization rates between the treated and the untreated oocytes only in the "no previous fertilization" group (60% vs 28%; P less than 0.05). A higher rate of fertilization of the treated oocytes was also seen in the immunologic infertility group, however, statistical significance was not achieved (50% vs 25%; P = 0.07). Only one clinical pregnancy was achieved in this group of 13 patients. We conclude that in this group of patients, removal of the cumulus prior to insemination may, in some cases, increase the fertilization potential of the oocyte.

The attainment of synchronous follicular development in human menopausal gonadotropin/human chorionic gonadotropin-stimulated cycles for in vitro fertilization (IVF) continues to be a perplexing problem. Two regimens of follicle stimulation for IVF cycles were, therefore, compared. Twenty-nine patients commenced human menopausal gonadotropin (hMG) therapy on day I of the menstrual cycle (Group I), while 30 women received hMG from the third day of the cycle (Group II). The hMG therapy was tailored to the individual patients's response, based on ultrasonographic measurements of follicular size and serum estradiol (E2) levels. Both groups of patients received a mean of 19.6±1.4 ampules of hMG over a mean of 6.1±0.2 days. The pattern of serum E2 and progesterone levels in the periovulatory and luteal phase was not affected by the day of initiation of hMG therapy, although Group I patients demonstrated lower (P

Patients' response to daily ultrasound scanning by either a transvaginal or a transabdominal method for the purpose of monitoring the ovarian response to gonadotropin therapy in an in vitro fertilization and embryo transfer program has been evaluated. A questionnaire was used to determine various aspects of these two procedures, sources of discontent, and the patients' preference. The vast majority of patients reported less discomfort and generally preferred the transvaginal over the transabdominal scanning method. The transvaginal method is easy to perform, affords excellent visualization of the pelvic organs, and in addition, is clearly preferred by patients over the transabdominal technique. We recommend its use in patients monitored for IVF-ET and for a variety of other clinical conditions requiring detailed evaluation of the pelvic organs.

In the last few years we have witnessed a real revolution in the knowledge and practices of human reproduction. In vitro ferti l ization and embryo transfer (IVF-ET) has opened new avenues in the treatment of infertility but has also offered new opportunities of research in the area of reproductive endocrinology and biology. The birth of Louise Brown in 1978 found the world community unready to cope with the complex legal and social issues raised by the application of IVF-ET for clinical and research purposes. In order to address those problems, many discussions on national and international levels have been organized and in some countries official committees have been appointed to propose the appropriate legislative actions. In this article we review the legal status of IVF-ET in Europe.

The First Annual Conference for in Vitro Fertilizat ion ( IVF) N u r s e C o o r d i n a t o r s , s p o n s o r e d by Serono Symposia USA and Baylor College of Medicine, was held March 21-23 , 1986, in Hous ton , Texas. The objectives of this program were to update the nurses ' knowledge of IVF technology, to provide utilization tools that maximize the administ ra t ive ro le o f the IVF nur se c o o r d i n a t o r , to broaden the nurses" understanding of the problems of the infertile couple, to improve counseling skills, and to form a ne twork of communica t ion among IVF nurse coordinators. Approximately 150 people at tended the conference. The group consisted primarily of IVF nurses.