Fertility and Sterility

OBJECTIVE: To assess the impact of VPR, ulipristal acetate (UPA) and placebo on HRQoL in women with UFs. DESIGN: Two multicenter, double-blind, randomized phase 2 studies examining the efficacy and safety of VPR compared with placebo (ASTEROID 1 and 2), and an active comparator (ASTEROID 2). MATERIALS AND METHODS: 309 and 172 women with UFs and heavy menstrual bleeding (HMB) were enrolled in ASTEROID 1 and 2, respectively. In ASTEROID 1, women received oral placebo or VPR 0.5 mg, 1 mg, 2 mg, or 4 mg once daily (OD) for 12 weeks, with follow-up at 24 weeks. In ASTEROID 2, women received VPR 2 mg, UPA 5 mg, or placebo OD for one or two 12-week treatment periods, with 12 weeks' follow-up. HRQoL was assessed using the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire and the Short-Form 36 Health Survey Version 2 (SF-36v2) during baseline (BL), end of treatment (EoT) and end of follow-up (EoFUP) visits. RESULTS: Across treatment groups in ASTEROID 1 at BL, the mean (SD) UFS-QoL total HRQoL scores were between 46.2 (24.1) and 49.9 (25.0)SF-36v2 physical component scores (PCS) were between 45.6 (7.3) and 47.5 (7.8), and SF-36v2 mental component scores (MCS) were between 43.3 (11.5) and 47.5 (8.3). All BL scores were in line with previously published data for women with UFs. 1 At EoT, the mean total and subscale UFS-QoL and SF-36v2 scores in all VPR-treated groups increased compared with BL. These increases were greater than those observed with placebo. The mean (SD) UFS-QoL total HRQoL scores increased to 83.2 (19.7) in the highest and 78.3 (24.0) in the lowest VPR dose group, versus 56.2 (24.8) in the placebo group. Mean (SD) SF-36v2 PCS and MCS increased to 51.7 (6.2) and 52.0 (8.9) in the lowest VPR dose group, and 53.7 (6.5) and 51.1 (8.9) in the highest VPR dose group, respectively. By comparison, the mean (SD) PCS and MCS at EoT in the placebo group were 48.4 (7.8) and 43.9 (12.2), respectively. The EoT UFS-QoL and SF-36v2 scores of women that received VPR were in the range of those previously published for healthy women without UFs 1 . Similar results were observed in ASTEROID 2. Mean UFS-QoL HRQoL and SF-36v2 BL scores increased continuously during treatment with VPR for up to 24 weeks, whereas increased scores were observed for the first 12 weeks with UPA but did not continue to 24 weeks (not statistically tested). The mean (SD) UFS-QoL total HRQoL scores across VPR dosage groups increased from between 78.5 (21.0) and 81.9 (16.4) after 12 weeks, to between 82.4 (17.5) and 85.6 (13.2) after 24 weeks' treatment. In the UPA group, this score decreased from 75.0 (19.6) at 12 weeks to 73.4 (20.8) at 24 weeks. In general, the mean UFS-QoL total HRQoL and SF-36v2 scores decreased only slightly between treatment cessation and EoFUP across active treatment groups in ASTEROID 1 (6 months) and 2 (3 months). CONCLUSIONS: In ASTEROID 1 and 2, increases in mean UFS-QoL and SF-36v2 HRQoL scores were observed alongside reduced HMB in women with UFs during active treatment with VPR and UPA for up to 24 weeks, and were sustained to EoFUP. Furthermore, by EoT, HRQoL scores increased to levels previously published for healthy women without UFs. 1 References: 1. Coyne KS, Margolis MK, Bradley LD, et al. Further validation of the uterine fibroid symptom and quality-of-life questionnaire. Value Health. 2012;15(1):135-142 SUPPORT: This study was funded by Bayer AG. Medical writing support provided by Huntsworth Health was funded by Bayer.

The group of patients who received urinary gonadotropins (n ¼ 117) for follicular stimulation had a significantly higher incidence of high perifollicular blood flow compared with that of the group who received recombinant FSH (n ¼ 114; 46.3% vs. 22.7%). The overall clinical pregnancy rate in patients stimulated with recombinant FSH was 10.91%, compared with 22.22% in the group stimulated with urinary gonadotropins. (Fertil Steril Ò 2009;92:1366-8. Ó2009 by American Society for Reproductive Medicine.

oxidant are associated with side effects of inflammation, such as cell injury and tissue damage. In view of these observations the objective of this study is to determine whether there is a difference in the expression levels of MPO in fibroblasts isolated from normal peritoneum and from adhesions, and whether this expression is modulated by hypoxia. DESIGN: Comparison of fibroblast primary cultures from normal peritoneum and adhesion tissues of the same patients. MATERIALS AND METHODS: We have obtained fibroblast primary cultures from normal peritoneum and adhesion tissues of the same patients. MPO synthesis by these fibroblasts was evaluated at mRNA utilizing the real-time RT/PCR and at the protein levels utilizing MPO ELISA kit. Fibroblasts were cultured under normal (20% O2) and hypoxic (2% O2) condition for 24 h. RESULTS: The studies herein define normal fibroblasts to have higher MPO mRNA (32 %; pϽ0.001) and protein (28%; pϽ0.001) levels than adhesion fibroblasts. Hypoxia decreased MPO mRNA by (35 %; pϽ0.001) and protein levels by (40%; pϽ0.001) in normal peritoneal fibroblasts to approximately of levels observed for adhesion fibroblasts while has no effects on MPO expression in adhesion fibroblasts. CONCLUSION: Our data suggests that hypoxia drive normal fibroblasts to mimic the adhesion fibroblasts by reducing their ability to produce MPO. Induction of MPO in adhesion fibroblasts to levels seen in normal fibroblasts may be important for the elimination of the adhesion phenotype during peritoneal healing.

Objective: To investigate whether WT1 protein expression is altered in eutopic endometrium of endometriosis patients. Design: Prospective study. Setting: University hospital. Patient(s): Patients with endometriosis and fertile women with macroscopically normal pelvic cavities. Intervention(s): During surgery, endometrial tissues were obtained from 59 patients with deep infiltrating endometriosis, ovarian endometriosis, or only superficial peritoneal endometriosis. Control endometrial tissue samples were obtained from 40 fertile women who underwent laparoscopic tubal ligation or reversal of tubal sterilization. Main Outcome Measure(s): The percentage of nuclear surface positively immunostained for WT1 (PI) and WT1-positive microvessel density. The PI was significantly lower in endometrial stromal cells from patients with deep infiltrating endometriosis than in stroma from control subjects during the midsecretory phase, whereas there was no significant difference between the two populations during the proliferative, early secretory, and late secretory phases. The PI was also significantly lower during the midsecretory phase in endometrial stromal cells from patients with ovarian endometriosis and superficial peritoneal endometriosis compared with control subjects. During the midsecretory phase, PI in endometrial stromal cells is down-regulated in patients with deep infiltrating endometriosis, ovarian endometriosis, and superficial peritoneal endometriosis compared with endometrium from healthy control subjects.

The minimum distance between the vaginal mucosal epithelium and the endometriotic glands was <1,000 mm in 30 patients (49.2%), <2,000 mm in 44 patients (72.1%), and <5,000 mm in 60 patients (98.4%). Our findings provided histologic evidence that excision of the posterior vaginal fornix was necessary to completely remove large rectovaginal endometriotic nodules. (Fertil Steril Ò 2009;91:1314-5. Ó2009 by American Society for Reproductive Medicine.

We investigated relationships between delay of surgical diagnosis and severity of disease in 95 patients with symptomatic deep infiltrating endometriosis. The delay before surgical diagnosis of deep infiltrating endometriosis was significantly longer for patients with advanced stage IV (revised American Society for Reproductive Medicine [ASRM] score Ͼ70) disease than for those with stage I, II, III, or IV (revised ASRM score Յ70)

Objective: To investigate whether genes that had been found to be differentially expressed in deep-infiltrating endometriosis and matched eutopic endometrium in our previous complementary DNA microarray study also are differentially expressed in ovarian endometriosis and matched eutopic endometrium. Design: Prospective study. Setting: University hospital in France. Patient(s): Patients with ovarian endometriosis. Intervention(s): During surgery, paired samples of tissue representing ovarian endometriosis and eutopic endometrium were obtained from 12 patients. Main Outcome Measure(s): Expression levels of messenger RNA for heat shock protein 90 alpha (HSP90A), chicken ovalbumin upstream promoter transcription factor 2 (COUP-TF2), prostaglandin E 2 receptor subtype EP3 (PGE 2 EP3), tyrosine kinase receptor B (TrKB), and 17␤-hydroxysteroid dehydrogenase type 2 (17␤HSD2; epithelial cells) and of platelet-derived growth factor receptor alpha (PDGFRA), protein kinase C beta 1 (PKC␤1), Janus kinase 1 (JAK1), mitogen-activated protein kinase kinase (MKK7), Sprouty2, -opioid receptor (MOR), and 5HTT (stromal cells) from ovarian endometriosis and matched eutopic endometrium were determined by using laser capture microdissection and real-time reverse-transcription polymerase chain reaction (RT-PCR) techniques. Result(s): Expression of PDGFRA, PKC␤1, JAK1, HSP90A, COUP-TF2, MOR, and 17␤HSD2 was significantly higher in ovarian endometriosis than in eutopic endometrium, whereas that of Sprouty2 and PGE 2 EP3 was significantly lower. There was no significant difference in mitochondrial RNA expression of MKK 7, TrKB, and 5HTT. Ovarian endometriosis might share several common molecules with deep-infiltrating endometriosis that act to sustain endometriotic lesions, whereas molecules involved in local endocrine control might be different between these two types of endometriosis.

Objective: To determine the pharmacokinetics and endometrial tissue levels of levonorgestrel when taken as a single dose of 1.5 mg either orally or vaginally by healthy women in the periovulatory phase of their menstrual cycle. Design: Prospective randomized study. Setting: Academic research institution. Patient(s): Thirty women with regular cycles allocated to control (n ϭ 5), oral (n ϭ 13), and vaginal (n ϭ 12) groups. Intervention(s): Blood samples were drawn before (0 time) and at 0.5, 1, 2, 4, 6, 8, 24, 48, and 168 hours after levonorgestrel administration. Endometrial samples were collected 24 and 168 hours after levonorgestrel administration. Main Outcome Measure(s): Plasma and endometrial tissue levels of levonorgestrel. Result(s): Plasma concentrations of levonorgestrel were significantly greater during the first 48 hours after oral administration. However, 7 days after levonorgestrel administration, the plasma levels were similar for both treatments (3-5 nmol/L). Compared with vaginal administration, oral administration resulted in higher peak plasma concentrations (C max 64 vs. 10.7 nmol/L), with a shorter time to reach the maximal concentrations (T max 1.4 vs. 6.6 hours) and with a greater AUC (509 vs. 175 nmol/L). Interestingly, the half-life of levonorgestrel was shorter after oral administration (25 hours vs. 32.6 hours). Levonorgestrel tissue concentrations were not related to the plasma levels. Levonorgestrel values tended to be higher in endometrial tissue after vaginal administration. The ratio between plasma and endometrial concentrations of levonorgestrel differed significantly between the groups. These data indicate that orally administered levonorgestrel achieves higher plasma levels sooner than vaginally administered levonorgestrel. However, plasma levels after vaginal administration are more sustained and were likely to be sufficient for ovarian suppression. Therefore, the vaginally administered levonorgestrel could be considered as an alternative option for emergency contraception. (Fertil Steril 2005

We examined the pharmacokinetics of a single dose of 1.5 mg of levonorgestrel when administered orally in two different formulations: two tablets of 0.75 mg or 50 minipills of 30 mg of levonorgestrel. Bioavailability of levonorgestrel with minipills was comparable to that with levonorgestrel tablets. These findings suggest that levonorgestrel-containing minipills can be considered as an alternative to standard levonorgestrel tablets for use in emergency contraception. (Fertil Steril Ò 2007;88:976-7. Ó2007 by American Society for Reproductive Medicine.

OBJECTIVE Accelerated placental maturation is regarded as a sign of vascular malperfusion and is often interpreted as a compensatory response by the placenta. In vitro embryo culture affects placental development. This study assessed placental maturation in spontaneous conceived and in vitro conceived pregnancies. METHODS Retrospective cohort study on a single center between 2014 and 2017. For this study, preterm placentas of singleton pregnancies between 24 and 36 weeks were considered. Routine placental examinations were retrospectively reviewed. RESULTS During the considered period, 423 placentas of singleton pregnancies were assessed. Three hundred ninety-six placentas were from spontaneous conception and 20 from in vitro fertilization and embryo transfer (IVF/ET). IVF/ET was significantly associated with accelerated villous maturation (AVM) and distal villous hypoplasia (DVH) (P&lt;0.05). CONCLUSIONS Placental AVM and DVH were significantly associated with in vitro fertilizatio...

Primary human uterine, cervical, and ectocervical stromal fibroblasts constitutively secrete hepatocyte growth factor (HGF), yet only uterine stromal fibroblasts increase HGF secretion in response to estradiol. Estradiol-induced HGF secretion by uterine stromal fibroblasts may have a significant effect on uterine cancer and endometriosis. (Fertil Steril Ò 2009;92:1107-9. Ó2009 by American Society for Reproductive Medicine.

OBJECTIVE: Successful ectopic grafting of neonatal testicular tissue onto immunodeficient mouse hosts has been reported in rodents and other mammals. Our goal is to evaluate the effects of different cryopreservative agents (CPA) on spermatogenesis and testosterone production of cryopreserved neonatal mouse testicular tissue using this model. DESIGN: Experimental basic animal study. MATERIALS AND METHODS: Neonatal mouse testes were cryopreserved in Hank's balanced salt solution (HBSS) þ 5% Fetal Bovine serum, and one of the following CPA's: (1) 0.7 M DMSO (Dimethyl sulfoxide), (2) 0.7 M Propylene glycol, (3) 0.7 M Ethylene glycol or (4) Glycerol using a computer-controlled freezer. Frozen-thawed testicular tissues from each group (n ¼ 4) were grafted onto castrated immunodeficient Ncr-nude mice. Fresh neonatal testis were also grafted, and served as positive control. Histological analyses of grafted tissue and host serum hormonal assays were assessed 12 weeks post-transplantation. RESULTS: Testes frozen with DMSO as the cryoprotectant showed superior results in graft survival and tissue maturation comparing to the other study groups. Serum testosterone from the DMSO group is also significantly higher than with the other three CPA's (P<0.05); and there is no significant differences between the DMSO and the freshly grafted control group in terms of host serum testosterone level. CONCLUSIONS: DMSO appears to be the best cryoprotectant among the agents tested in this study. Neonatal mouse testes can be efficiently cryopreserved with the computer-controlled slow rate freezing using DMSO as the primary CPA.

Uterine rupture is a life threatening condition for both the mother and her fetus. It may be seen in the second trimester usually after induction for pregnancy termination in a scarred uterus. Spontaneous rupture in the second trimester before labor is a very rare condition. Here, we report a case of uterine rupture at 23-week pregnancy due to elevated uterine pressure with a history of laparoscopic myomectomy one year before admission. She was symptomatic for diffuse abdominal pain and the ultrasonographic image was interpreted as amniotic band. Four days later, because of deterioration of the patient and fetal bradycardia urgent laparotomy was performed. Fundal rupture with fibrotic borders suggested that a chronic event was seen. Laparoscopic myomectomy has advantages over laparatomy but the possibility of uterine rupture in following pregnancies should not be underestimated. Therefore, repair of the myometrium should be carefully assessed.

In a group of placentas from patients with preeclampsia or fetal growth restriction, reduced annexin V gene expression in those carrying the M2 haplotype was observed. This is the first ''ex vivo'' demonstration that annexin V gene expression in placentas is dependent on the M2 haplotype. (Fertil Steril Ò 2009;91:940-2.

In the electrophysiology laboratory (EPH-Lab) data collection of implanted devices is mandatory for documentation and clinical reporting. At present, computerized systems are not commonly used in the EPH-Lab, but they can allow clinicians to obtain a proper documentation from an integrated information system, gathering data from ambulatory activity, wards and EPH-Lab archives. The aim of our work was to create an informative system to exchange clinical information using HL7 Clinical Document Architecture (CDA) release 2, defined in HL7 V3 standard. EPH-Lab facility has been introduced as part of our hemodynamic information system (SIE) in order to track work flow, device implantations, electrophysiologic studies, interventional electrophysiology procedures and electronic medical records for anesthesiology.

Traditional assessment of ROS production using luminol and lucigenin detected significant increase in ROS after the exposure of mature and immature sperm fractions to H 2 O 2 . CONCLUSIONS: Exposure of human spermatozoa to exogenous hydrogen peroxide is associated with increased intracellular ROS which can be detected by either flowcytometry or chemiluminescence probes. Mature spermatozoa may be more susceptible to exogenous H 2 O 2 exposure as it showed increase in both intracellular O 2 -(DHE%) and H 2 O 2 (DCFH%).

Objective: To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI). Design: Retrospective cohort. Setting: Single infertility center. Patient(s): A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included. Intervention(s): NC TDI or OS TDI with either clomiphene citrate or letrozole. Main Outcome Measure(s): Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome. Result(s): Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%). Ovarian stimulation in TDI cycles resulted in a <4% increase in clinical and <1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination.

Objective: To design and evaluate an ET simulator to train Reproductive Endocrinology and Infertility (REI) fellows' techniques of ET. Design: Simulation model development and retrospective cohort analysis. Setting: Not applicable. Patient(s): Patients undergoing IVF. Intervention(s): Simulation model evaluation and implementation of ET simulation training. Main Outcome Measure(s): Pregnancy rates. Result(s): The REI fellow and faculty evaluation responses (n ¼ 19/21 [90%] ) of the model demonstrated realistic characteristics, with evaluators concluding the model was suitable for training in almost all evaluated areas. A total of 12 REI fellows who performed ET were analyzed: 6 before ET trainer and 6 after ET trainer. Pregnancy rates were 31% in the initial 10 ETs per fellow before simulator vs. 46% after simulator. One of six pre-ET trainer fellows (17%) had pregnancy rates R40% in their first 10 ETs; whereas four of six post-ET trainer fellows had pregnancy rates R40% in their first 10 ETs. The average number of ETs to obtain >40% pregnancy efficiency was 27 ETs before trainer vs. 15 ETs after trainer. Pregnancy rates were similar in the two groups after 20 ETs, and collective terminal pregnancy rates were >50% after 40 ETs. Conclusion(s): Embryo transfer simulation improved REI fellow pregnancy rates in their first 10 transfers and led to a more rapid ET proficiency. These data suggest potential value in adopting ET simulation, even in programs with a robust history of live ET in fellowship training.

The primary purpose of our study was to investigate the influence of cesarean scar diverticulum on the reproductive outcome of fresh and frozen embryo transfer after in vitro fertilization/intracytoplasmic sperm injection. The secondary aim of our study was to assess the impact of endometrial cavity fluid on the reproductive outcome of embryo transfer among patients with an existing cesarean scar diverticulum. DESIGN: This was a retrospective cohort study. 1275 patients who had a history of cesarean delivery between January 2013 and December 2018 at our Institute of Reproductive Medicine were included. The study included 847 cycles of fresh embryo transfer and 1213 cycles of frozen embryo transfer. According to the results of transvaginal gynecological ultrasound, the patients were divided into two groups: cesarean scar diverticulum group(n¼169) and cesarean delivery without diverticulum group(n¼1106). According to the presence of endometrial cavity fluid during the endometrial preparation process of frozen embryo transfer, patients with the cesarean scar diverticulum were divided into two subgroups: endometrial cavity fluid group(n¼36) and non-endometrial cavity fluid group(n¼108). MATERIALS AND METHODS: The basic characteristics, pregnancy outcome and delivery outcome of the included patients were collected from the database of our institute and compared. Binary logistic regression analysis was performed to adjust confounding factors when the baseline demographic variables of two groups of patients were significantly different. The propensity score was computed by accounting for the effect of confounding factors. Propensity scores were matched 1:1 using the nearest neighbor matching method. The matched data set was used in logistic regression. RESULTS: There were no significant differences in the baseline variables between the cesarean scar diverticulum group and the control group. The implantation rate, clinical pregnancy rate and live birth rate of fresh embryo transfer in the cesarean section diverticulum group was significantly lower than the control group(19.6% vs 32.5%,p¼0.001; 25.7% vs 43.0%,p¼0.001; 17.8% vs 31.6%,p¼0.004). The implantation rate, clinical pregnancy rate and live birth rate of frozen embryo transfer in the cesarean section diverticulum group was also significantly lower than the control group (27.1% vs 34.5%,p¼0.015; 32.7% vs 41.2%,p¼0.021; 23.5% vs 31.4%,p¼0.021). 21.20% cycles of frozen embryo transfer among the cesarean section scar diverticulum group developed endometrial cavity fluid during endometrial preparation. The baseline variables were similar between the endometrial cavity fluid and non-endometrial cavity fluid group after propensity score matching. The odds of clinical pregnancy and miscarry were similar between two subgroups before and after adjustment for covariates (adjusted OR0.45( 0.18-1.12), P¼0.086; adjusted OR 0.75(0.14-3.95), P¼0.736). CONCLUSIONS: The presence of cesarean section scar diverticulum was detrimental to embryo implantation and had a bad impact on reproductive outcomes of fresh and frozen embryo transfer.

Our metformin-based treatment experience especially with life-style modifications seemed to be effective for all symptoms of the hyperandrogenic ovarian dysfunction PCOS phenotype during 12 months. The addition of Vitamin D3 have not shown significant advantages in our results. We recommend metformin with life-style modifications for all women with hyperandrogenic ovarian dysfunction syndrome because it is generally acceptable, safe, and cost-effective. Our answer to the question in the title is YES. If select symptoms don't respond well, additional treatment modalities may be added to it; until better treatment forms emerge. In this work we used metformin treatment as an equivalent of treating insulin resistance. Stronger agents are on the rise but they are not expected to replace metformin soon. On the other hand, do we know if metformin helped through diminishing insulin resistance, or by something else of its many unknown qualities? Further comments. 1. The PCOS name is inappropriate, erroneous, biased, misleading; should have been changed decades ago; also in view of the male equivalent of the syndrome (just a suggestion for the common name: hyperandrogenic subfertility). 2. The use of hormonal contraceptives. As if the 'modern' variants were less anti-androgenic (causing acne-seborrhoea, weight gain; suspicion for increasing insulin resistance). Do we know how the long-term anovulation during hormonal contraceptive treatment affects the reproductive ability of users in a disorder where anovulation is a principal problem? Patient information should include the answer.

On the background of controversial claims regarding the origin of reproductive medicine, this paper aims at determining as to whether writings created during the the Middle Ages can be considered a contribution to reproductive sciences. To accomplish this goal, the original writings of Hildegard of Bingen are analysed to determine whether she contributed to the advancement of reproductive medicine. An analysis of Hildegard's work reveals that she discusses in an evidence-based fashion male and female infertility. The topics of female infertilty include fertilization, sperm capacitation, menstruation, and menopause. The topics of male infertility include semen, erectile dysfunction, ejaculatory dysfunction, and nocturnal emission.

Fifty-five women with mild to moderate Alzheimer's disease were randomly assigned to tacrine (n ϭ 26) or HRT (n ϭ 29). In the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n ϭ 3) or together with micronized progesterone to patients with uteri (n ϭ 26).

The transfer of the GVs recovered from the mitochondriallydamaged oocytes into control ooplasts resulted in 66.7% (44/66) being reconstituted and 77.2% (34/44) undergoing maturation. The majority (84.6%) (22/26) had a normal MII spindle. CONCLUSION: Selective artificial mitochondrial damage was induced only at a degree capable of halting maturation with consequent spindle abnormalities, but was not subtle enough to induce aneuploidy once maturation had occurred. Healthy mitochondrial replenishment by nuclear transfer can reverse maturational block brought by damaged mitochondria.

Polycystic ovary syndrome (PCOS) usually presents during the reproductive years with hyperandrogenism, oligo-anovulation and/or polycystic ovaries on ultrasonography. The identification of PCOS was largely restricted to these reproductive years earlier. However, with improved understanding of the disease, currently there is data to describe the PCOS phenotype from infancy up to the post menopausal years. The spectrum of presentation of PCOS phenotype changes across the life span of a given individual. Early identification of high risk individuals during childhood and pre-pubertal years will enable the clinician to incorporate therapeutic or lifestyle preventive measures at an earlier age. Intra uterine programming of the foetus exposed to elevated testosterone and gestational hyperglycemia are also being shown to contribute significantly to the phenotypic expression in later years. The data on post menopausal women with PCOS is also increasing. Contrary to what was expected, except for a subgroup of women with persistent hyperandrogenism, available data does not seem to indicate an increase in cardiovascular morbidity or all cause mortality among post menopausal women with previous history suggestive of PCOS.

Objective: To evaluate the results of hysteroscopic placement of an intratubal device for permanent birth control in 85 women in an outpatient setting. Design: Prospective, observational study. Setting: Private university hospital. Patient(s): Eighty-five premenopausal women who asked for tubal sterilization by hysteroscopy between July 2002 and July 2003. Intervention(s): Hysteroscopic placement of titanium-dacron intratubal devices in an outpatient setting. Main Outcome Measure(s): Procedure feasibility without anesthesia, success rate of device implantation, patient satisfaction, and confirmation of correct placement. Result(s): Successful placement was achieved in 81 patients (95%). Mean time elapsed between the start of hysteroscopy, placement of devices, and removal of optics was 9 minutes (range, 1-35 minutes). No intraoperative or postoperative complications were detected. Of 81 patients, 75 (93%) had abdominal x-ray performed at the third month; bilateral correct placement was confirmed in all of them. Essure is a safe, effective, and minimally aggressive procedure with satisfactory patient acceptance that does not require anesthesia or hospitalization. It seems to be a good alternative to laparoscopic tubal sterilization. (Fertil Steril 2004;82:196 -9.

CONCLUSION: The calculated daily dose of the TCDS was equivalent to approximately 30 mg EE and exposure in the TCDS was substantially less than the 35 ug combination OC. Daily EE exposure with the lowdose TCDS (AG200-15) is well within the range reported for low dose OC.

Chtf18-null male and female mouse gonads are much smaller and morphologically abnormal compared to those of their wildtype adult littermates. Fertility is significantly impaired in both male and female mice. Seminiferous tubules from Chtf18-null males demonstrate an overall deficiency of spermatocytes and a significant paucity of spermatids and spermatozoa. Some areas of seminiferous tubules are almost devoid of spermatogenic cells. The tubules also contain large multi-nucleated and aberrant-appearing spermatogenic cells. Ovaries from Chtf18-null females are smaller and contain fewer follicles than wild-type females. All stages of follicle development are seen, but many of the follicles appear to be degenerating and contain aberrant-appearing cells. Surface spread nuclei from Chtf18-null mouse gonads reveal a clear chromosomal defect during meiosis. In addition, the morphological phenotype of Chtf18 loxP/loxP ; TNAP Cre mice, in which Chtf18 is deleted only in germ cells, is indistinguishable from that of Chtf18-null gonads, indicating that Chtf18 is required in the germ line. CONCLUSIONS: CTF18/Chtf18 plays a significant role in mammalian gametogenesis and fertility through a function in meiosis. Supported by: Grants from the NIH (HD 01256 and HD 34449 to K.M.B.; HD 33834 to T.A.J).

Objective: To explore the effects of 17b-estradiol (E 2 ) on cytoskeletal remodeling and motility of endometrial stromal cells (ESC) and Ishikawa cells and to characterize the role of focal adhesion kinase (FAK) in these processes. Design: In vitro study of cytoskeletal remodeling and cellular morphology and motility in ESC or Ishikawa cells. Setting: University research center. Patient(s): Endometrial samples obtained from women requiring endometrial biopsies. Intervention(s): Treatments with E 2 and multiple inhibitors of signaling pathways. Main Outcome Measure(s): Activation of FAK, actin remodeling, membrane morphology, cell motility, and invasion. Result(s): Estrogen induces a rapid and concentration-related FAK phosphorylation in ESC and Ishikawa cells. In this time frame, FAK localizes to the plasma membrane at sites of focal adhesion complexes formation, as shown by immunofluorescence. Phosphorylation of FAK in the presence of estrogen depends on the recruitment of both estrogen receptor a and estrogen receptor b and of a rapid G protein-dependent signaling to c-Src and phosphatidylinositol 3-OH kinase. Activation of FAK in ESC and Ishikawa cells is required for estrogeninduced horizontal migration and invasion of three-dimensional matrices of endometrial cells. Conclusion(s): Estrogen enhances cytoskeletal and membrane remodeling in ESC and Ishikawa cells by controlling FAK, thus resulting in enhanced cell motility and invasion. These findings may have clinical relevance for the development of new therapeutic strategies for the prevention or control of endometrial diseases. (Fertil Steril Ò 2011;95:722-6. Ó2011 by American Society for Reproductive Medicine.

Background: Morphological aspect of polycystic ovaries (PCO) is a very common finding in an IVF center population: this includes PCOS patients identified in 18-25% of the couples presenting with infertility and so called "sonographic PCO only" the prevalence of which has been estimated as high as 33% in asymptomatic patients. Finding the optimal first intention IVF protocol for polycystic ovaries patients is still challenging in order to improve the controlled ovarian hyperstimulation (COH) outcome while avoiding ovarian hyperstimulation syndrome (OHSS). It has been suggested that women with PCO would benefit from a longer period of pituitary down-regulation. The purpose of this study was to compare an extended duration of OCP pretreatment with a classic GnRH agonist protocol. Methods: A single center prospective non-randomized study was performed from January 2009 to December 2010 in the Lille University Hospital including 113 women diagnosed with PCO(S) according to the Rotterdam ultrasonographic criteria and undergoing their first IVF attempt. Comprehensive hormonal and ultra-sonographic assessments were collected during COH in these patients. LH and androgen suppression and dynamics of follicular growth were compared between the two protocols as well as the COH outcome in terms of oocyte/embryo number and quality, implantation and pregnancy rates. Results: No significant difference was observed between the two groups concerning dynamics of follicular growth and hormonal values. Clinical and ongoing pregnancy rates were significantly lower in the OCP group despite same oocyte and embryo quality. Nevertheless, the cumulative pregnancy rate did not differ between the two groups. The incidence of OHSS was not statistically significant. Conclusions: Extended duration of OCP pretreatment, as a first intention IVF protocol for PCO patients, does not improve the pattern of follicular growth nor the oocyte and embryo quality.

ABSTRACTPurposeExpanded carrier screening (ECS) analyzes dozens or hundreds of recessive genes for determining reproductive risk. Data on clinical utility of screening conditions beyond professional guidelines is scarce.MethodsIndividuals underwent ECS for up to 110 genes. 537 at-risk couples (ARC), those in which both partners carry the same recessive disease, were invited to a retrospective IRB-approved survey of their reproductive decision making after receiving ECS results.Results64 eligible ARC completed the survey. Of 45 respondents screened preconceptionally, 62% (n=28) planned IVF with PGD or prenatal diagnosis (PNDx) in future pregnancies. 29% (n=13) were not planning to alter reproductive decisions. The remaining 9% (n=4) of responses were unclear.Of 19 pregnant respondents, 42% (n=8) elected PNDx, 11% (n=2) planned amniocentesis but miscarried, and 47% (n=9) considered the condition insufficiently severe to warrant invasive testing. Of the 8 pregnancies that underwent PND...

Objective: To present a case of ovarian hyperstimulation syndrome occurring after evacuation of a spontaneously conceived hydatidiform molar pregnancy. Design: Case report. Setting: University-affiliated teaching hospital. Patient(s): A 19-year-old nulliparous woman who underwent vacuum curettage for a complete hydatidiform molar pregnancy was admitted to our hospital with ovarian hyperstimulation syndrome and large bilateral pleural effusions. Intervention(s): Intravenous fluid, deep vein thrombosis prophylaxis, placement of bilateral chest tubes. Main Outcome Measure(s): Management of ovarian hyperstimulation syndrome. Result(s): Ultrasonography and computed tomography showed large multicystic ovaries, marked ascites, and large pleural effusions that required placement of bilateral chest tubes. She had recovered by hospital day 14. Conclusion(s): Ovarian hyperstimulation syndrome may develop in women who have undergone treatment for a hydatidiform mole, and serious complications may develop rapidly. (Fertil Steril Ò 2009;92:395.e1-e3. Ó2009 by American Society for Reproductive Medicine.

BACKGROUND: Dyslipidemia and insulin resistance (IR), occurring in most infertile women with polycystic ovarian syndrome (PCOS), increase the risk of cardiovascular disease (CVD) and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. MATERIALS AND METHODS: Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES) criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu), insulin and lipid profile levels triglycerides (TGs), total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) were calculated. IR was also calculated using homeostasis model assessment (HOMA)-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Chara...

Objective: To map the X-chromosome and autosome breakpoints in women with balanced X-autosome translocations and primary amenorrhea, searching candidate genomic loci for female infertility. Design: Retrospective and case-control study. Setting: University-based research laboratory. Patient(s): Three women with balanced X-autosome translocation and primary amenorrhea. Intervention(s): Conventional cytogenetic methods, genomic array, array painting, fluorescence in situ hybridization, and quantitative reverse transcription-polymerase chain reaction. Main Outcome Measure(s): Karyotype, copy number variation, breakpoint mapping, and gene expression levels. Result(s): All patients presented with breakpoints in the Xq13q21 region. In two patients, the X-chromosome breakpoint disrupted coding sequences (KIAA2022 and ZDHHC15 genes). Although both gene disruptions caused absence of transcription in peripheral blood, there is no evidence that supports the involvement of these genes with ovarian function. The ZDHHC15 gene belongs to a conserved syntenic region that encompasses the FGF16 gene, which plays a role in female germ line development. The break in the FGF16 syntenic block may have disrupted the interaction between the FGF16 promoter and its cis-regulatory element. In the third patient, although both breakpoints are intergenic, a gene that plays a role in the DAX1 pathway (FHL2 gene) flanks distally the autosome breakpoint. The FHL2 gene may be subject to position effect due to the attachment of an autosome segment in Xq21 region. The etiology of primary amenorrhea in balanced X-autosome translocation patients may underlie more complex mechanisms than interruption of specific X-linked candidate genes, such as position effect. The fine mapping of the rearrangement breakpoints may be a tool for identifying genetic pathogenic mechanisms for primary amenorrhea.

oocytes, normal prolactin and thyroid function, successful pituitary downregulation (E2 Ͻ40 pg/ml), at least four follicles Ն16 mm with E2 Ն150 pg/ml/follicle, endometrium Ն7 mm, embryo availability, absence of severe ovarian hyperstimulation]. Only the first cycle was included if there were multiple cycles. IRB approval was not required as the protocol did not vary from our routine. Materials/Methods: Mid-luteal pituitary down-regulation was achieved with leuprolide acetate (0.5-1.0 mg) and followed by ovarian stimulation with human menopausal gonadotropins. Transvaginal oocyte aspiration was performed 36 hours after human chorionic gonadotropin (hCG, 10,000 IU) was administered, and embryos were transferred three days later. P support (50 mg IM daily) began on the evening of aspiration. Day zero signifies ovulation, i.e. oocyte retrieval. Study days correspond to day of hCG injection, ET, and early, mid, and late-luteal phase. Serum E2 and P levels were obtained by chemiluminescence on days -2, ϩ3, ϩ7, ϩ11 and hCG was determined on day ϩ14. E2:P ratios were calculated. Statistical analysis for pregnant (n ϭ 39) vs. non-pregnant (n ϭ 35) cycles and clinical (n ϭ 33) vs. negative/non-clinical pregnancies (n ϭ 41) was done with two-tail group t, chi-square or Mann-Whitney tests as applicable. Results: Pregnant vs. non-pregnant cycles were similar in baseline and in-vitro parameters, except for cryopreservation. Mean E2 was significantly higher on day ϩ11 for pregnant vs. non-pregnant cycles (257 Ϯ 251 vs. 57 Ϯ 40 pg/ml; P Ͻ 0.0001), and for clinical pregnancies vs. negative/nonclinical pregnancy cycles (238 Ϯ 200 vs. 57 Ϯ 40 pg/ml; P Ͻ 0.0001). Mean P was not statistically related to cycle outcome. Mean E2:P ratios for pregnant vs. non-pregnant cycles were dramatically higher on day ϩ11 (P Ͻ 0.0001) and marginally higher on day ϩ3 (P ϭ 0.03). Mean E2:P for clinical pregnancies vs. negative/non-clinical pregnancy cycles were significantly higher only on day ϩ11 (P Ͻ 0.0001). In non-pregnant cycles, mean E2 on day ϩ11 plus 3 standard deviations (99% about the mean) was below 200 pg/ml (range 16 -199). E2 level Ͼ200 pg/ml on luteal day ϩ11 was highly predictive of conception. Conclusions: According to our data, late-luteal E2 level and E2:P ratio are predictive of pregnancy following IVF-ET with pituitary down-regulation. An E2 level Ͼ200 pg/ml on luteal day ϩ11 is highly predictive of conception. A prospective randomized study of vigorous flushing of cervical canal with culture medium prior to embryo transfer.

This study evaluated the differentially modulated expression of vascular mediators in oocyte donors after hCG vs. GnRHa triggering, trying to understand ovarian hyperstimulation syndrome pathophysiology. Donors who received GnRH agonist triggering showed a statistically significant decrease in vascular endothelial growth factor in follicular fluid and in mRNA expression in granulosa cells, with no differences in angiopoietin 2 and vascular endothelial cadherin levels in serum or foicular fluid. This differential regulation of vascular endothelial growth factor by hCG might explain the higher likelihood of ovarian hyperstimulation syndrome following hCG administration compared with GnRH agonists. (Fertil Steril Ò 2011;95:2517-9. Ó2011 by American Society for Reproductive Medicine.

The epidemic of iatrogenic multiple births as a result of infertility treatment are responsible for an unacceptable high incidence of maternal, perinatal and childhood morbidity and mortality. Healthcare costs due to infertility therapy are too high and this may lead to social and political concern. The introduction of single embryo transfer (SET) was a real breakthrough, but was only accepted in most European countries and Japan. The United States, Latin America and most developing countries still have high multiple pregnancy rates. The most common argument for not performing SET are the high costs associated with ART procedures. Competition between ART centres to achieve and publish the highest success rates is another major factor. But things have changed: vitrification methods for cryopreservation are responsible for a better survival and increased success rate with frozen-embryo transfer, our knowledge to select the best embryo for SET is increasing and the growing concern of h...

Objective: To determine the expression of endometrial endothelial nitric oxide synthase (eNOS) protein and ␣ v ␤ 3 integrin in patients with and without endometriosis. Design: Case-control cohort study. Setting: University-based tertiary care center. Patient(s): Endometrial biopsy samples were obtained from 9 fertile women with regular cycles and 30 infertile women with varying severity of endometriosis. Peritoneal fluid levels of nitric oxide were determined in 13 infertile women with a normal pelvis and 12 infertile women with endometriosis. Main Outcome Measure(s): Expression of eNOS and ␣ v ␤ 3 integrin protein in the endometrium and peritoneal fluid levels of nitric oxide. Results: In patients with endometriosis, expression of eNOS was significantly increased in the glandular and luminal epithelium, with no significant changes in the stroma. Peritoneal fluid levels of nitric oxide were unchanged, and expression of ␣ v ␤ 3 integrin expression in glandular and luminal epithelium was significantly decreased compared with controls. A significant negative correlation was observed between luminal expression of eNOS and ␣ v ␤ 3 integrin and between glandular expression of eNOS and luminal expression of ␣ v ␤ 3 integrin. The nitric oxide pathway may play a role in the pathogenesis of endometriosis. (Fertil Steril 2002;78:860 -4.

OBJECTIVE: To evaluate the efficacy of sub-endometrial autologous stem cell implantation in women with severe degree of Asherman's Syndrome. (Efficacy is defined as resumption of menstruation). DESIGN: Prospective, Case series. MATERIALS AND METHODS: Patients with Asherman's Syndrome (n¼6) where other treatment options had failed; bone marrow aspiration was done from iliac crest under local anesthesia .Bone marrow (30 ml) was aspirated using bone marrow aspiration needle (Jamshidi, 11 G). It was collected in heparinised syringes. The Isolation of Mononuclear cells was done by Ficoll density separation method at Stem cell facility.Harvested stem cells were implanted in sub-endometrial zone as identified by transvaginal scan through trans-myometrial route using ovum pick up needle (Cook,17 G) under I.V.sedation.Post implantation patients were given oral Estradiol Valerate (Progynova, Schering manufacturer) 2mg thrice a day for six weeks followed by cyclic Estrogen & progesterone therapy for 3 months(Medroxy-progesterone acetate, Serum Institute of India LTD.) 10 mg once daily from day21-day27. Women were followed up at 3, 6 and 9 month intervals by trans-vaginal ultrasound for the endometrial thickness. RESULTS: Descriptive statistics and statistical analysis of study variables was carried out using STATA version 9.0. Changes in endometrial thickness values due to treatment was compared using 't' -Paired test to see the significant increase in ET values at 3 months, 6 months and 9 months. Mean AEStandard deviation of ET values at 3 months (4.05AE1.40), 6 months(5.46AE1.36) and 9 months (5.48AE1.14) were significantly (P<0.05) increased from pre treatment level (1.38AE0.39). The mean (AESD) of MNC counts was 103.3 (AE20.45) and ranged from 76 Â10 6 to 128Â10 6 . Similarly the mean (AESD) of CD34 was 203642 (AE269274) and ranged between 10640 and 640090 with median value 58800. CONCLUSION: Haemopoitic stem cells implantation results in endometrial regeneration in Asherman Syndrome.

Objective: To investigate the impact of early cleavage (EC) on embryo quality, implantation, and live-birth rates. Design: Prospective cross-sectional study. Setting: Multicenter study. Patient(s): Seven hundred embryo transfers and 1,028 early-stage human embryos. Intervention(s): None. Main Outcome Measure(s): Implantation according to the presence of EC and embryo quality. Result(s): The presence of EC is associated with embryo quality, especially in cycles with autologous oocytes. However, the use of EC as an additional criterion for selecting an embryo for transfer does not appear to significantly improve likelihood of implantation. Furthermore, embryos that presented EC had live-birth rates per implanted embryo similar to those that did not show any sign of cleavage. Conclusion(s): At least for conventional embryo culture and morphologic evaluations, the additional evaluation of EC in embryos may not be valuable to improve embryo implantation. (Fertil Steril Ò 2014;101:981-7. Ó2014 by American Society for Reproductive Medicine.

Aim: The aim of present review is to provide a comprehensive view of the literature regarding the clinical efficacy and safety effects of supplementation of Progestogens during luteal phase in the first trimester. Methods: A literature search was performed using electronic databases like Pub med/Medline to identify from 1980 to 2015. The search yielded around 27 original studies and review articles. The search yielded around 31 clinical studies and reviews. Results: Progestogen use for luteal support in assisted reproductive technologies is associated with significantly higher rates of live birth or ongoing pregnancy than placebo or no treatment. Based on findings from randomized control studies and meta-analysis, similar ongoing pregnancy and miscarriage rates have been observed for dydrogesterone (oral) when compared to intra-vaginal micronized progesterone (MCP) and between MCP intra-vaginal and MCP intra-muscular for luteal phase support. However, dydrogesterone (oral) exhibited an overall higher ongoing pregnancy rate compared to MCP oral (30% vs. 11%). There was no evidence to indicate that maternal exposure to Progestogens during pregnancy increased the risk for birth defects. Conclusion: The relative effectiveness, safety, optimal route and duration of oral, vaginal, and intra-muscular progestogen formulations is a topic of ongoing debate. Future investigations with longer follow-ups and larger sample sizes comparing different routes of administration, dosages, and timing of administration are warranted.

OBJECTIVE: Donor sperm is commercially available in unwashed (ICI) and prewashed (IUI-ready) preparations. There is limited data regarding the efficacy of on site processed ICI versus IUI-ready samples when used for intrauterine inseminations. Our hypothesis was that IUI-ready donor specimens provide a higher total motile sperm count (TMSC) at the time of IUI and a higher subsequent pregnancy rate. DESIGN: This retrospective cohort study included all patients who underwent donor IUI from 2005-2012 at an academic REI practice. MATERIALS AND METHODS: All patients aged 19-42 years who underwent donor IUI were identified and data abstracted on type of donor sperm sample, age, indication, use of fertility medications, and other covariates. The primary outcome, TMSC at the time of IUI, was collected, as were the secondary outcomes of chemical and clinical pregnancy rates and live birth rate. Parametric and non-parametric measures were used to analyze outcomes. RESULTS: Of the total 353 donor IUI cycles, 71 (20%) were IUI-ready samples and 282 (80%) were ICI samples. Indication for therapy was male factor (34%), same sex (39%) and single female (26%). The majority of cycles were performed with oral (73%) or injectable (14%) ovulation agents. The median TMSC was not significantly different between the IUI-ready (18x10^6) and ICI (15x10^6) preparations (p¼0.08). The incidence of a TMSC <10x10^6 was 11% for IUI-ready samples and 20% for ICI samples (p¼0.09). The OR for a TMSC <10x10^6 was 0.51 (p¼0.10, 95%CI: 0.23-1.13) for IUI-ready vs ICI samples. No difference in biochemical, clinical, or live birth rates were seen between the two groups. CONCLUSION: IUI-ready donor specimens had a higher TMSC and lower incidence of TMSC <10x10^6 compared to ICI samples, although the difference was not statistically significant in our study population. It does not appear that IUI-ready specimens provide a significant benefit over ICI specimens in centers where ICI samples can be processed post-thaw for IUI procedures.

Objective: To find the most informative method of XY bivalent detection for spermatozoa presence in testicular tissue of nonobstructive azoospermic men. Design: Prospective study. Setting: Institute for the Study of Fertility, affiliated with a university medical faculty. Patient(s): Thirty-five men with azoospermia, divided into subgroups: complete maturation arrest (n ϭ 10), mixed atrophy (n ϭ 14), and obstructive azoospermia (n ϭ 11). Intervention(s): Testicular tissue biopsies for sperm extraction. Main Outcome Measure(s): Histopathologic and cytology analyses and the presence of XY bivalent formation by fluorescence in situ hybridization probes for centromere and subtelomere regions. Immunostaining of ␥-H2AX for sex body (SB) identification was also performed. Result(s): Percentage of spermatocytes with X-Y pairing, determined by the paired short arms pseudoautosomal region, was significantly higher than percentage of spermatocytes with long arm telomeres in proximity in all three groups. The parameter of q telomeres in proximity was the most sensitive index to distinguish one group from the other. Stained SB by ␥-H2AX was found to be the most informative for the prediction of successful sperm retrieval. Alignment of the X and Y axes that occurs in the late zygotene stage probably precedes the stage in which the SB is stained by ␥-H2AX. Consequently, because of the nonhomogeneity of the testis, when histology raises suspicion of complete maturation arrest percentage of spermatocytes with stained SB is the most informative parameter for sperm presence on sperm retrieval. (Fertil Steril 2006;86:106 -12.

Objective: Ethylene glycol has been successfully used as a cryopreservative for vitrification of mammalian embryos including human. Due to its lower molecular weight (62.07 g/mol) compared to other cryopreservatives, it is possible to get a better result if EG is used for cryopreservation of mammalian embryos in slow freezing, instead of propandiol (PROH). This study was carried out: (1) to compare permeability and toxicity of EG with those of PROH using mouse embryos, (2) to investigate the efficiency of EG in relation to embryo cleavage stage, and (3) to determine whether pregnancy outcome is improved when human embryos are frozen by using EG instead of PROH. Design: A prospective study on cryopreservation of human embryos using EG in slow freezing was performed, from Jan. 1999 to Dec. 1999. As a control group, the retrospective data of the cryopreserved human embryos using PROH, from Jan. 1998 to Dec. 1998, were used. Materials and Methods: Mouse embryos were stepwise exposed to 1.5M PROH or EG with 0.2M sucrose and then some of the embryos were cryopreserved and the others were stepwise washed and cultured. Extra human embryos after embryo transfer were also cryopreserved using 1.5M PROH or EG with 0.2M sucrose in controlled slow freezing. Results: When 2-cell mouse embryos were exposed to EG (nϭ352) or PROH (nϭ358), there was a significant difference in the percentages of embryos developed to expanded blastocyst between EG (64.4%, PϽ.05) and PROH groups (53.8%). The mouse embryos exposed to PROH showed a cytoplasmic shrinkage, but the embryos exposed to EG did not. Two-, 4-, and 8-cell embryos were frozen/thawed with PROH or EG, the overall survival and developmental rates of the embryos in EG group were 69.1 and 33.1%, respectively, which were significantly higher than the rates (9.1 and 3.0%, PϽ.05) of the embryos in PROH group. The survival rates of 2-cell mouse embryos in both EG and PROH groups (76.1 and 15%, PϽ.05) were significantly higher than the rates of 4-(66.7 and 3.7%) or 8-cell embryos (64.7 and 8.7%). However the developmental rate of 8-cell embryos in EG and PROH groups (63.8 and 9%, PϽ.05) were significantly higher than the rates of 2-(6.4 and 0%) and 4-cell embryos (29.3 and 0%). The survival rate of human embryos frozen/thawed with EG (72.2%, PϽ.05) was significantly higher than the rate of embryos frozen/thawed with PROH (54.7%). Although the pregnancy rate of embryos in EG group (31.4%, 11/35 cycles) was higher than the rate of embryos in PROG group (20.5%, 7/34 cycles), but there was no statistical significance in the difference of the rates. Conclusions: We observed that lower toxicity and higher permeability of EG compared to PROH. Cryopreservation of human embryos using EG increased the survival and pregnancy rates compared to the use of PROH. Therefore EG may be a better substitute for PROH to cryopreserve human embryos in slow freezing protocol.