Total Amount Of Gonadotropins Research Articles

Comparing Naltrexone and Metformin Pretreatment for Inducing Ovulation in Patients With Polycystic Ovary Syndrome in Intrauterine Insemination Cycles

Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women. Hyperinsulinemia and insulin resistance are normally observed in PCOS patients and metformin is used to treat this disease. The evidence indicates that the opioid system plays a role in the pathogenesis of the PCOS. Based on the above-mentioned explanation, the present study evaluated the role of opioid antagonist (naltrexone) in PCOS-induced infertility compared to metformin. Materials and Methods: Totally, 120 patients afflicted with PCOS were assigned to three groups based on Rotterdam diagnostic criteria, with a body mass index (BMI) of 25-30 kg/m2 . The first group received naltrexone (50 mg/d) for 8 weeks. In addition, the second group were injected with metformin 1000 and then 1500 mg/d for the first and seventh weeks, respectively. Finally, the third group entered the intrauterine insemination (IUI) without prior therapeutic treatment. Then, the groups were compared in terms of the amount of estradiol produced per day of human chorionic gonadotropin injection and the total amount of gonadotropin needed, the number and size of the adult follicles, the number of days of taking the drug, and incidence of pregnancy-induced abo Results: Based on the results, the mean of infertility duration was not significant among the three groups (P=0.782). Further, the mean fasting insulin level between the metformin and control groups represented a significant difference (P=0.045). The average number of days to trigger patients in the 3 groups was not significant (P=0.346). Although the average number of follicles between metformin and naltrexone groups was not significant, it was higher in the naltrexone group. Finally, the average BMI of the naltrexone group after the treatment was lower compared to before treatment (P≤ 0.001). Conclusions: In general, the number of receiving days and the dose of the drug in the naltrexone group was lower compared to the metformin group. Furthermore, the number of mature follicles in both ovaries and the serum estradiol level in the naltrexone group was higher compared to the metformin group.

Effect of orlistat intervention on in vitro fertilization/intracytoplasmic sperm injection outcome in overweight/obese infertile women

Objective This retrospective study sought to evaluate the effect of orlistat intervention on the outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in overweight/obese infertile women. Methods Twenty-nine overweight/obese patients undergoing IVF/ICSI for the first time were treated with orlistat intervention (orlistat group). Another 29 patients with matched age and body mass index (BMI) were included in the control group at a ratio of 1:1. Clinical data of both groups were collected, and the clinical baseline data, IVF/ICSI cycle information and embryo transfer outcome were compared between groups by Student’s t-test or chi-square test when appropriate. Results The 29 patients in the orlistat group completed 37 embryo transfer cycles, and the 29 subjects in the control group completed 38 embryo transfer cycles. There was no significant difference in the clinical baseline data or IVF/ICSI cycle data between the two groups (p > .05). In the end, 22 transfer cycles in orlistat group obtained clinical pregnancies, 5 obtained biochemical pregnancies and 10 had non-pregnancies. As for the control group, 15 transfer cycles obtained clinical pregnancies, 15 achieved biochemical pregnancies and 8 had non-pregnancies. The clinical pregnancy rate of the orlistat group was significantly higher than that of the control group (59.46% versus 39.47%, p = .004), but there was no significant difference in the live birth rate between the two groups (54.05% versus 36.84%, p > .05). Conclusions Orlistat intervention for overweight/obese infertile women receiving IVF/ICSI treatment will increase the clinical pregnancy rate, without affecting the total amount of gonadotropins, ovarian stimulation time or the follicular output rate (FORT).

SUBTLE ENDOMETRIAL ABNORMALITIES DO NOT AFFECT THE PREGNANCY RATE IN FRESH ICSI CYCLES

The study aimed to determine whether the presence of subtle endometrial abnormalities discovered by office hysteroscopy (OH) affects the pregnancy rate in fresh intracytoplasmic sperm injection (ICSI) cycles. A prospective cohort study included women undergoing their first ICSI cycles was performed in assisted reproductive technology unit. Patients were divided into two groups: patients with subtle endometrial abnormalities diagnosed by OH (group 1, n=78), and patients with normal uterine cavity (group 2, n=122). OH was conducted post-menstrual and subtle abnormalities detected included hypervascularization, petechiae, mucosal elevation, micropolyps, pale endometrium and single adhesion band. The main outcome measures were clinical pregnancy and implantation rates The most common subtle abnormality observed was pale endometrium in 35.9% of cases. Both groups were comparable regarding the baseline clinical data and endometrial thickness. Additionally, total amount of gonadotrophins used, duration of stimulation, peak estradiol concentrations, peak endometrial thickness, number of mature follicles and number of embryos transferred were not significantly different between both groups. The implantation rate was similar in both groups (2.35 ± 0.83 vs. 2.22 ± 0.84, p=0.465). Also, the pregnancy rate was similar in both groups (38.5% vs. 33.6%, p=0.067) Subtle endometrial abnormalities diagnosed by OH do not negatively affect pregnancy and implantation outcomes in fresh ICSI cycles.

P–684 Impact of GnRH antagonist pretreatment on oocyte yield after ovarian stimulation: a retrospective analysis

Abstract Study question Does a 3-day pretreatment course with a GnRH antagonist in the early follicular phase increase the number of oocytes in a GnRH antagonist stimulation protocol? Summary answer The administration of 3 days of GnRH antagonist before starting ovarian stimulation in a GnRH antagonist protocol increases the number of COCs (Cumulus-Oocyte-Complexes). What is known already The GnRH antagonist protocol is characterized by higher gonadotropin and E2 serum levels at the start of ovarian stimulation (OS), compared with a long pituitary down regulation protocol. The unsuppressed FSH level at the start of a GnRH antagonist cycle allows the initial growth of follicles before addition of exogenous FSH, which may result in asynchrony of the follicular cohort. Menstrual administration of a GnRH antagonist can inhibit follicle growth and improve homogeneity of recruitable follicles. Previous studies showed a trend toward higher numbers of COCs and improved maturation and fertilization rates of retrieved oocytes. Study design, size, duration Retrospective single center crossover study, including consecutive women enrolled in an IVF program in a university hospital from January 2011 to December 2020. All women underwent one standard GnRH antagonist stimulation cycle (“standard cycle”) and one GnRH antagonist stimulation cycle preceded by early administration of GnRH antagonist for 3 days (“pretreatment cycle”). Women with basal progesterone levels >1.5ng/ml, and women undergoing oocyte freezing, oocyte donation or PGT were excluded. In total, 427 patients were included. Participants/materials, setting, methods Women were included when the pretreatment cycle occurred within a time interval of < 12 months following the start of stimulation in the standard cycle. The primary outcome was the total number of COCs. Main results and the role of chance The average female age was 35.1 ± 4.7 years. Indications for fertility treatment included unexplained infertility (34.3%), male-factor infertility (33.3%), age (16.9%), PCOS (8.2%) and endometriosis (2.6%). All cycles were divided into two groups: group 1 (standard, 427 cycles) and group 2 (pretreatment, 427 cycles). The mean duration of stimulation was similar in both groups (10.3 vs 10.3 days, p = 0.2). The starting dose of gonadotropin (196.8 vs 234.9IU, p < 0.001) and total amount of gonadotropin used (2000.7 vs 2415.2IU, p < 0.001) were higher in group 2. The total number of obtained COCs (6.2 vs 8.8 p < 0.001) and the number of mature oocytes (4.2 vs 6.4 p < 0.001) were significantly higher in group 2. The Generalized estimating equation (GEE) multivariate regression analysis showed that the pretreatment strategy had a significant positive effect on the number of COCs (coefficient 2.8, p value <0.001 after adjusting for the confounders age, indication of infertility, stimulation dose, type and total amount of gonatropins used). Limitations, reasons for caution Despite the large dataset, the presence of biases related to the retrospective study design cannot be excluded. Besides, the impact of GnRH pretreatment on pregnancy rate cannot be assessed because of the crossover design. Wider implications of the findings: A 3-day course of GnRH antagonist pretreatment increases the number of COCs obtained after OS. Furthermore, since the initiation of OS in a GnRH antagonist protocol relies on the occurrence of spontaneous menses, addition of three days of GnRH antagonist pretreatment may enhance scheduling flexibility without reducing efficacy. Trial registration number Not applicable

The effects of multiple controlled ovarian hyperstimulation over a 2-year period on ovarian reserve and reactivity: a retrospective clinical study

To evaluate the effects of controlled ovarian hyperstimulation (COH) on ovarian reserve function during in vitro fertilization and embryo transfer (IVF-ET). From August 2018 to August 2020, the medical records of patients who received IVF-ET in the Department of Reproductive Medicine, Beijing Gynaecology and Obstetrics Hospital, Capital Medical University were analyzed retrospectively. Among them, 372 patients received 2 cycles of COH, 54 patients received 3 cycles, and 13 patients received 4 cycles. The levels of follicle-stimulating hormone (FSH), the number of antral follicles, levels of anti-Müllerian hormone (AMH), the total amount of gonadotropin (GN), the time of ovulation induction, the number of eggs obtained, the number of available embryos, and the number of high-quality embryos cycles were compared in different treatment. The age of female patients did not significantly affect the levels of AMH or FSH during menstruation, nor the number of antral follicles before ovulation induction (P>0.05). However, with an increase in age, an increase in the number of controlled COH cycles was observed. In patients who underwent 2 COH cycles, the number of high-quality embryos in the second cycle increased significantly compared to the first cycle (P<0.05). However, there were no significant differences in the ovulation induction time, the number of eggs, the GN dosage, and the number of available embryos (P>0.05). In patients with 3 treatment cycles, the GN dose used in the third cycle was significantly lower than that used in the first cycle (P<0.05). There were no significant differences in the ovulation induction time, the number of eggs obtained, and the quality of embryos (P>0.05). In patients with 4 treatment cycles, significant differences were observed in the ovulation induction time between the first and the fourth controlled COH cycle (P<0.05). However, no significant differences were detected in GN dosage, ovulation induction time, the number of eggs obtained, the number of available embryos, and the quality of embryos (P>0.05). Ovarian reserve function was not significantly affected in patients with up to 4 ovarian stimulation cycles.

Effect of Different Ovulation Induction Regimens on Pregnancy Outcome of Patients with Endometriosis and Infertility Treated with In Vitro Fertilization and Transplantation

To explore the effect of different ovulation induction regimens on pregnancy outcome of patients with endometriosis and infertility treated with in vitro fertilization and transplantation. From December 2016 to December 2019, a total of 324 patients with endometriosis and infertility were selected as subjects. After the same in vitro fertilization treatment, three protocols (super long protocol, modified long protocol and antagonist protocol) were studied retrospectively. Baseline, total Gonadotropin dosage, Gonadotropin days, Luteinizing hormone, progesterone and follicle stimulating hormone levels (U/L), oocyte retrieval and embryo status, clinical pregnancy rate, live birth rate and abortion rate were compared among the three groups. The total number of days and total amount of Gonadotropin in the super long protocol group were lower than those in the modified long protocol group and antagonist group (p 0.05). In addition, the number of retrieved ovums, mature ovums, normal cleavage and excellent embryos in the modified long protocol group was the highest (p<0.05), followed by the super long protocol group (p<0.05). Compared with the other two groups, the pregnancy rate and live birth rate were significantly increased (p<0.05) and the abortion rate was significantly decreased (p<0.05). Finally, the pregnancy rate, live birth rate and abortion rate of the modified long protocol group were higher than those of the antagonist protocol group. The pregnancy rate and live birth rate of super long protocol were higher than those of modified long protocol and antagonist protocol and the abortion rate was lower. The total number of Gonadotropin days and the total amount of Gonadotropin in super long protocol group were lower, which had the advantages of clinical significance. It was a kind of ovulation induction formula worthy of promotion for patients with endometriosis and infertility casen.

Effects of waiting time between failed fresh cycle embryo transfer and the next frozen embryo transfer on pregnancy outcomes in assisted reproductive technology.

To explore how waiting time after failed fresh cycle embryo transfer affects the pregnancy outcomes of the next frozen embryo transfer (FET). A retrospective analysis was carried out on the data of women who had received at least one FET after a failed fresh embryo transfer between January 2013 to December 2019. The women were grouped based on the "time" of the first FET, referring to the period between a failed fresh embryo transfer and the beginning of the next cycle of FET. This time is divided into two classes: immediate (<90days after the failed fresh embryo transfer) and delayed (≥90days after failed fresh embryo transfer). The following parameters were investigated: clinical pregnancy rate; biochemical pregnancy rate; ectopic pregnancy rate; and non-pregnancy rate. A total of 293 cases of fresh embryo transfer cycles were included. No significant differences in the number of obtained oocytes, total number of FET, and the total amount of gonadotropin were seen between the immediate and delayed fresh embryo transfer groups. The pregnancy outcomes of the two groups were similar. The duration of waiting time between failed fresh embryo transfer and the next FET does not affect pregnancy outcomes.

Required amount of rFSH, HP-hMG and HP-FSH to reach a live birth: a systematic review and meta-analysis

STUDY QUESTIONIn women undergoing IVF or ICSI cycles, do recombinant gonadotrophins differ from urinary-derived highly purified human menopausal gonadotropin (HP-hMG) or highly purified follicle-stimulating hormone (HP-FSH) in the total amount of gonadotrophins required to reach a live birth?SUMMARY ANSWERThe difference between recombinant and urinary-derived HP-hMG or HP-FSH in the required amount to reach a live birth in IVF/ICSI cycles appears small.WHAT IS KNOWN ALREADYAt present, gynecologists can choose between recombinant FSH (rFSH), urinary-derived HP-hMG and HP-FSH. These products are equally effective and safe, but it is unknown how these gonadotrophins compare in terms of IU required to reach a live birth.STUDY DESIGN, SIZE AND DURATIONWe conducted a search in Medline, Embase and CINAHL up to July 2018. We included randomized controlled trials (RCTs) that compared rFSH with HP-hMG or HP-FSH for ovarian stimulation in couples scheduled for IVF or ICSI treatment. From each randomized trial, we extracted the outcome data and information on participants, methods, interventions and funding.PARTICIPANTS/MATERIALS, SETTING AND METHODSWomen undergoing ovarian stimulation with rFSH, HP-hMG or HP-FSH were included. We extracted data for the mean amount of gonadotrophins with SD, clinical pregnancy rate, live birth rate and cumulative live birth rate per woman from the included RCTs. We summarized these outcomes by calculating the individual and pooled mean difference (MD) or relative risk (RR) with 95% CI. We used the Review Manager software to perform the meta-analyses. We applied a random effect model to pool the data. We estimated the total amount of gonadotrophins used per extra live birth by STATA 14.2 and R software.MAIN RESULTS AND THE ROLE OF CHANCEA total of 28 studies with 7553 women were included in this review, of which 24 studies provided information on the total amount of gonadotrophins per woman who started an IVF/ICSI cycle. The total amount of gonadotrophins varied significantly between studies. The MDs in total amount were −37 IU (seven studies; N = 3220; 95% CI, −115 to 41; I2 = 68%) for rFSH versus HP-hMG and −31 IU (17 studies; N = 3629; 95% CI, −290 to 228; I2 = 97%) for rFSH versus HP-FSH. For rFSH versus HP-hMG, the RR for clinical pregnancy, live birth and cumulative live birth were 0.90 (95% CI, 0.81–1.00), 0.88 (95% CI, 0.78–0.99) and 0.91 (95% CI, 0.80–1.04), respectively. For rFSH versus HP-FSH, the RR for clinical pregnancy and live birth were 1.03 (95% CI, 0.94–1.13) and 1.03 (95% CI, 0.90–1.18), respectively; the data on cumulative live birth rate were lacking. The estimated difference in mean gonadotrophin amount per extra live birth was 789 IU (95% CI, −9.5 to 1570) for rFSH versus HP-hMG and −365 IU (95% CI, −2675 to 1945) for rFSH versus HP-FSH.LIMITATIONS, REASONS FOR CAUTIONThere was severe heterogeneity in the total amount of gonadotrophins between studies. A small fraction of women did not start gonadotrophin treatment; this was usually not accounted for in the provided mean amount of gonadotrophins per study and might have affected the averaged total amount of gonadotrophins but is unlikely to have affected the differences in the amount between rFSH and HP-hMG or HP-FSH.WIDER IMPLICATIONS OF THE FINDINGSThe differences in the required amount to reach a live birth between rFSH, HP-hMG and HP-FSH appear to be small. Decision-making should be based on convenience, availability, actual costs and patient preferences.STUDY FUNDING/COMPETING INTERESTSThe authors declare no conflict of interest. No external funding was either sought or obtained for this study.REGISTRATION NUMBERProspero CRD42016038238

Weigh the pros and cons to ovarian reserve before stripping ovarian endometriomas prior to IVF/ICSI: A meta-analysis.

PurposeTo explore the effects of conservative surgery for endometriomas on ovarian responsiveness during assisted reproductive technology (ART) and provide reproductive and gynecological doctors with a more reliable reference program for the treatment of endometriomas.MethodsA literature search was performed by searching the PubMed, Embase, Cochrane Library, Web of Science and Science Direct databases. Studies with inter- and intra-patient comparisons of ovarian responses and oocyte quality between operated and unoperated ovaries and that met the inclusion criteria were retrieved, and the data from the outcome measures were extracted and pooled for this meta-analysis.ResultsTwenty-one published studies (2649 ART cycles) were included. The total amount of gonadotropin (Gn) used (inverse variance (IV):0.48; 95% confidence interval (CI): [0.13, 1.82], P = 0.0007) was significantly increased in the women with endometriomas who had a history of cystectomy. The estrogen (E) level on the day of hCG administration (IV: -0.29; 95% CI: [-0.41, -0.17], P<0.00001), the number of mature or dominant follicles (IV: -1.17; 95% CI: [-1.51, -0.82], P<0.00001) and the total number of oocytes retrieved (IV: -1.78; 95% CI: [-2.38, -1.17], P<0.00001) were significantly decreased in the women with endometriomas who had a history of cystectomy. The duration of stimulation (IV: 0.02; 95% CI: [-0.09, 0.13], P = 0.77), the total number of formed embryos (IV: -0.06; 95% CI: [-0.17, 0.04], P = 0.25), the pregnancy rate(IV:0.98;95%CI[0.82,1.18], P = 0.83) and the live birth rate(IV:0.93;95%CI[0.70,1.23], P = 0.61)were not statistically different between the two groups. Similar intra-patient results were found in the number of mature or dominant follicles (IV: -0.88; 95% CI: [-1.25, -0.52], P<0.00001) and the total number of oocytes retrieved (IV: -3.48; 95% CI: [-4.77, -2.19], P<0.00001).ConclusionART might be a better therapeutic method for ovarian endometrioma-related infertility than cystectomy.

High Progesterone levels in the beginning of ICSI antagonist cycles and clinical pregnancy: still a concern?

ObjectiveIn controlled ovarian hyperstimulation (COH) using antagonist cycles, an incomplete luteolysis could happen after an inefficient previous luteolysis. Since antagonist cycles are frequent today, this study aims to access the impact of serum progesterone in the beginning and at the end of stimulation, and pregnancy outcomes.Methodssingle-center cohort study, 461 fresh embryo transfers in ICSI antagonist cycles. Serum progesterone levels was measured in the beginning of COH (P4i) and on hCG day (P4f) using threshold values of 1.5ng/mL. Four groups were created: Group 1, P4i and P4f ≤ 1.5; Group 2, P4i ≤ 1.5 and P4f > 1.5; Group 3, P4i > 1.5 and P4f ≤ 1.5 and Group 4, P4i and P4f > 1.5. The clinical pregnancy rate (CPR) and live birth rates (LBR) were the primary outcomes.ResultsThe number of cycles per group was: 393, 51, 6 and 11, respectively. Group 1 was considered the expected normal, while group 4 represented the persistence of higher levels. There was no difference in age, basal FSH and Estradiol, days of stimulation endometrium thickness and total amount of gonadotropins between group 1 versus group 4. However, significant differences occurred in embryological and clinical outcomes between these 2 groups.ConclusionThe impact of serum progesterone in the beginning of stimulation and pregnancy outcomes is a matter of concern. Basal elevated levels could help identify patients that will repeat it on hCG day, being probably a marker to define a freeze-all strategy to these cycles.

Flexible GnRH antagonist protocol vs. long GnRH agonist protocol in patients with polycystic ovary syndrome treated for IVF: comparison of clinical outcome and embryo quality.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, primarily affecting women of the reproductive age. The aim of the study was to assess the clinical efficacy and embryo quality in flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in comparison to the long GnRH agonist protocol in PCOS women undergoing in vitro fertilization (IVF). This prospective, randomized study was conducted at the Department of Gynecology and Obstetrics, Clinical Center Niš, Serbia, between 2013 and 2014. The treatment included either a flexible GnRH antagonist protocol (n = 45, antagonist group) or a long GnRH agonist protocol (n = 45, agonist group). The length of the stimulation, total amount of gonadotropins used, as well as the average number of the aspirated and mature oocytes were higher in the agonists group. The endometrial thickness was also greater in the agonists group. A higher number of Class I and Class IV embryos were obtained after the agonist treatment and higher number of Class II and Class III embryos were obtained after the antagonist treatment. Pregnancy, implantation, and miscarriage rates were comparable between the groups. The GnRH antagonist protocol in PCOS patients has a pregnancy rate comparable to that of the GnRH agonist protocol. Since this protocol has a lower rate of complications and is more convenient for patients, we believe that the GnRH antagonist protocol should be used as the first-line treatment for PCOS patients in an IVF program.

Getting Older Women Pregnant: Contemporary Thoughts.

For women of advanced age with abnormally increased FSH levels, standardized hormonal stimulation often represents a cost-intensive procedure with a low success rate. It is well established now that with mild ovarian stimulation, there is a greater percentage of good-quality eggs (although a smaller number) than with higher-dose conventional stimulation. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotropins used and the mean number of oocytes retrieved. The proportion of high-quality and euploid embryos seems to be higher compared with conventional stimulation protocols, and the pregnancy rate per embryo transfer is comparable. Moreover, the reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. The low number of embryos available for transfer poses a great challenge in the management of older women going in for IVF. A potential management of these older women is to create a sufficient pool of embryos by accumulating vitrified good-grade embryos over several minimal stimulation and natural cycles. At the end of the accumulation process, these embryos can be subjected to a preimplantation genetic screening using next-generation sequencing and then the pool would have only chromosomal normal embryos with maximal chances of implantation. This would potentially make the chances of success for older women similar to normal responders. This management, however, is unthinkable without an outstanding vitrification program. The option of accumulating embryos has become a promising reality with the advent of vitrification technologies.

Different stimulation protocols for oocyte cryropreservation in oncological patients: a retrospective analysis of single university centre

Objective: To analyze the results obtain in cancer patients who receive the same controlled ovarian stimulation protocol, started in two different moments of the menstrual cycle, follicular or luteal phase. The stimulation is performed before cancer treatment in order to preserve fertility through oocytes cryopreservation.Study design: The study is a retrospective analysis about 25 cancer patients at our centre, Department of Reproductive Medicine of University of Pisa, in order to preserve their fertility before cancer treatment. Patients are divided into two groups depending on the menstrual cycle phase, follicular or luteal phase, at the moment of first examination. Standard stimulation protocol with gonadotropins is administered in the follicular group, whereas in the second group we use GnRH (gonadotropin-releasing hormone) antagonist before gonadotropins administration in order to have a rapid luteolysis. The outcome measures are the number of days needed before starting procedure, duration of stimulation, cumulative dosage of gonadotropins number of oocyte retrieved and percentage of mature oocytes.Results: Any difference showed between two groups based on days of stimulation, total amount of gonadotropins administered and the number of good mature quality oocytes was retrieved. The real difference is the number of days needed to start the procedure, lesser in the luteal group.Conclusions: This study suggests that oocytes can be obtained before cancer treatment, irrespective of menstrual cycle phase without compromising the efficacy of procedure. Moreover, starting ovarian stimulation anytime during menstrual cycle allows the patients to not postpone the beginning of cancer treatment. Different stimulation protocols, according to different kinds of disease, are available in order to obtain the maximum results without any complication for patients.

Letrozole protocols are associated with improved oocyte yield in BRCA positive patients

To determine whether letrozole-based protocols improve ovarian response in BRCA-positive women. Retrospective cohort study. Patients with BRCA mutations undergoing IVF for fertility preservation (breast cancer patients) or preimplantation genetic diagnosis (no history of cancer) were included. Patients with breast cancer who had received prior chemotherapy were excluded. Patients were stratified into two groups: those who received letrozole continuously throughout their cycle and those who received conventional GnRH agonist- or antagonist-based protocols without the addition of letrozole. Outcomes assessed included total and mature oocyte yield, oocyte maturity rate, fertilization rate, and cancellation rate. Statistical analysis included student’s t-test, chi-square and Fisher’s exact tests. P<0.05 was deemed statistically significant. 53 cycles in 37 BRCA positive patients who underwent an IVF cycle between July 2006 and September 2013 were analyzed. The proportion of BRCA1 and BRCA2 positive patients was comparable between the groups. In patients with partners, fertilization was attempted with ICSI in 14 letrozole cycles and 22 conventional stimulation cycles. The two groups were similar in age, BMI, baseline AMH, antral follicle count at cycle start, total days of stimulation, and total amount of gonadotropins used. Total and mature oocyte yield was significantly higher in the letrozole group. There was no difference in percent of mature oocytes between the two groups. Fertilization rate was not different between oocytes exposed to letrozole compared to conventional stimulation protocols. More cycles were cancelled in the conventional group, although this difference was not statistically significant.Tabled 1Letrozole(n=25)Conventional(n=28)PAge (years)33.6±3.733.5±4.40.95BMI (kg/m2)20.1±6.622.0±2.70.14AMH at Start (ng/mL)1.8±1.42.7±3.40.40AFC at Start†4.6±1.74.4±1.30.62Total Gonadotropins2761±14923129±16270.4Total Days of Stimulation9.4±3.48±6.50.17# Cancelled Cycles1 (4%)3 (10.7%)0.61#Ooocytes17.6±910.1± 4.70.001*#Mature Oocytes12.0±6.47.8±50.01*Fertilization Rate0.66±0.340.74±0.260.45†AFC/ovary= 1=2-3 follicles<10mm, 2=4-6<10mm, 3=7-10<10mm, 4=>10<10mm. Open table in a new tab †AFC/ovary= 1=2-3 follicles<10mm, 2=4-6<10mm, 3=7-10<10mm, 4=>10<10mm. IVF protocols that include letrozole yield comparable fertilization rates and an improved oocyte yield in BRCA-positive women. The addition of letrozole to the BRCA-positive patient’s IVF protocol should be considered regardless of cancer or estrogen-receptor status. Further studies are needed to determine whether these findings hold true in a larger cohort and to investigate pregnancy outcomes.

Aromatase inhibitor co-treatment with gonadotropin reduces the dose of gonadotropn and peak estradiol level without compromising IVF outcomes in high responder patients

WITHDRAWN E2 (pg/ml) on hCG day 3850 765 4272 1508 1.5 ng/ml) or low (P4 3000 pg/ml on the hCG day). Patients were stimulated with daily doses of 100-150 UI of recombinant FSH (Puregon , MSD) starting on day 2-3; GnRH antagonist was added when the leading follicle reached a diameter of 14 mm (Cetrotide, 0.25 mg/day, Merck-Serono) and a single bolus of 250 mg of rhCG (Ovitrelle, Merck-Serono) was administered to induce oocyte maturation. FERTILITY & STERILITY Chi-squared test and ANOVA were applied to detect statistical differences; p<0.05 was considered statistically significant. RESULTS: Regarding the influence of progesterone concentration on clinical outcomes in presence of high estradiol levels, we did not find significant differences in any of the clinical variables analyzed. However, we observed statistical differences in E2 and P4 levels on the day of hCG between the two groups of the study. CONCLUSION: Our data suggest that in high responder women with estradiol levels over 3000 pg/ml, progesterone levels do not affect IVF results. We confirmed the close link between E2 and P4 as we observed that high E2 levels are significant correlated with high P4 levels. These results lead us to conclude that, regardless the progesterone levels attached during the cycle in high responders, clinical outcomes are not affected. O-358 Wednesday, October 16, 2013 04:45 PM COMPARING THE EFFICACYAND SAFETY OF GnRH AGONIST (LEUPROLIDE) WITH HCG TRIGGER VERSUS GnRH ANTAGONIST (GANIRELIX)WITHTRIPTORELIN TRIGGER IN PATIENTS OFPCODUNDERGOING IVFTREATMENT. R. Sharma, F. Rehman, N. Nakshtramalini. IVF and Reproductive Medicine, Max Hospital, New Delhi, India. OBJECTIVE: To determine the ideal protocol for PCOD patients undergoing IVF treatment. DESIGN: Retrospective analysisJan 2010 –Jan 2013. MATERIALS AND METHODS: 70 PCOS patients (according to Rotterdam criteria), who underwent IVF/IVF-ICSI cycles between Jan 2010 – Jan 2013 were evaluated retrospectively for the type of protocol used, amount and duration of gonadotrophin use, cost, no.of oocytes, fertilization rate, cleavage rate,embryo quality, clinical pregnancy rate and complication rate. RESULTS: The profiles of the patients in both groupswere comparable. Cost was almost same in both groups though there was reduction in the total amount of gonadotrophins used in the antagonist cycles. There was Reduction in the treatment days with analogue in the antagonist group (average 4.5 in antagonist versus 21 days in the agonist group). Duration of stimulation (9.5 versus 11.2 days) and total gonadotrophin required (1425 versus 1680 IU) were lower in the antagonist compared with agonist protocol. Mean no. of oocytes (COC’s) were less,(16.26 in the antagonist group versus 19.45 in the agonist group) therefore mean number of fertilized oocytes and consequent no. of embryos per patient were less in the antagonist group though fertilization rate(57.17%versus 58.09%) and cleavage rate(88.53%versus89.38%) were similar. There was no evidence of a statistically significant difference in clinical pregnancy rate between the two groups (36.66%in antagonist group versus 37.5%in the agonist group). There was significantly lower incidence of OHSS in the antagonist group. In agonist group, 3 patients had severeOHSS; due towhich embryo transfer had to be postponed .In antagonist group no patient had severe OHSS. In antagonist group one patient had empty follicles at the time of Oocyte retrieval with no embryos to transfer subsequently. CONCLUSION: The use of GnRH antagonists may be considered more advantageous because of more patient comfort and decreased risk of OHSS with good clinical outcome in high responder patients. O-359 Wednesday, October 16, 2013 05:00 PM THE FIRST SUCCESSFUL LIVE BIRTH FOLLOWING PREIMPLANTATION GENETIC DIAGNOSIS FOR TYPE I CITRULLINEMIA USING POLYMERASE CHAIN REACTION. C.-H. Kim, K.-H. Lee, J.-H. Cho, J.-M. Kim, G.-H. Kim, H.-W. Yoo. Obstetrics

IVF Lite: Is this the Future of Assisted Reproduction?

Over the last two decades, easier and less-expensive stimulation treatments have been largely replaced by more complex and more demanding protocols. Since the mid-nineties, long-term gonadotropin-releasing hormone (GnRH) agonist stimulation protocols have been widely used. Such lengthy expensive regimens are not free from short- and long-term risks and complications. The use of controlled ovarian stimulation to obtain multiple eggs for Assisted Conception has resulted in a compromise. In terms of the risk of Ovarian hyperstimulation syndrome (OHSS) [1]. Expense [1]. Multiple pregnancies [1]. Wastage of or the need for cryopreservation of surplus embryos [1]. Even some women with apparently normal menstrual cycles might become “poor responders” when administered with follicular stimulants [1]. Incidence of oocyte aneuploidy is artificially raised after stimulation [2]. Consequently, with evolution of patient-friendly Assisted Conception procedures, routine IVF (IVF), is being challenged by simpler methodologies. These include: Natural cycle IVF (nIVF) [2]. Minimal stimulation IVF (msIVF) [3, 4]. IVF Lite (minimal stimulation IVF + vitrification + accumulation of embryos + remote embryo transfer) (msIVF + ACCUVIT + rET) [5]. A minimal stimulation IVF cycle is defined either as. a stimulation regimen in which gonadotropins are administered at a lower-than-usual dose and/or for a shorter duration throughout a cycle in which GnRH antagonist is given as co-treatment [6, 7], or a stimulation in which oral compounds (e.g., anti-estrogens) are used either alone or in combination with gonadotropins and GnRH-antagonists [8, 9]. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotropins used and the mean number of oocytes retrieved [3]. The proportion of high quality and euploid embryos seems to be higher compared with conventional stimulation protocols, and the pregnancy rate per embryo transfer is comparable [2]. Moreover, the reduced costs, the better tolerability for patients, and the less time needed to complete an IVF cycle make mild approaches clinically and cost effective over a given period of time. However, further prospective randomized studies are needed to compare cumulative pregnancy rates between the two protocols. Natural cycle IVF(nIVF), with minimal stimulation, has been recently proposed as an alternative to conventional stimulation protocols in normo- and poor-responder patients [2, 10, 11].

A common Asn680Ser polymorphism in the follicle-stimulating hormone receptor gene is not associated with ovarian response to gonadotropin stimulation in patients undergoing in vitro fertilization

To assess the role of the variant p.Asn680Ser in the follicle-stimulating hormone receptor (FSHR) gene in determining ovarian response in patients undergoing in vitro fertilization (IVF) treatment. Prospective observational study. Tertiary referral center for reproductive medicine. Women (n = 421) undergoing their first cycle of controlled ovarian stimulation for IVF and 83 healthy, ethnically matched controls. Baseline pelvic ultrasound and blood tests taken on days 2 to 3 of the cycle for assessment of baseline hormones and for DNA extraction. Genotypes for FSHR p.Asn680Ser determined using TaqMan allelic discrimination assay, and ovarian response to gonadotropin treatment classified as normal, poor, or overresponse based on the number of oocytes retrieved. The FSHR p.Asn680Ser genotype frequencies were similar in IVF patients and controls. The number of oocytes retrieved was comparable between patients with different FSHR receptor genotypes. The total amount of gonadotropin used was also similar in all the genotype groups. A logistic regression analysis showed nonstatistically significant twofold difference in the distribution of genotypes between the groups with poor and normal ovarian response. The variant FSHR p.Asn680Ser was not shown to be predictive of ovarian response, but clinically relevant differences cannot be ruled out.

Ovarian stimulation in women with high and normal body mass index: GnRH agonist versus GnRH antagonist

In modern society, obesity has become a major health problem and has been associated with impaired fertility. The aim of this study is to assess the role of obesity in women undergoing controlled ovarian hyperstimulation (COH) stimulated either with GnRH agonists or with GnRH antagonists. Records of 463 women undergoing in vitro fertilization (IVF) treatment were reviewed. The influence of body mass index (BMI) on treatment outcome was examined, after accounting for differences in stimulation protocols. In the agonist group (286 patients), the total amount of gonadotropins used was significantly higher in patients with a BMI ≥ 25 kg/m2, when compared to those with a normal BMI. The same result was found in the antagonist group (177 patients). No significant differences were found in length of stimulation, number of oocytes retrieved or number of embryos transferred. In both the antagonist and the agonist group, the number of clinical pregnancies was found to be higher in patients with normal BMI, suggesting that obesity could impair the ovarian response to exogenous gonadotropins. Considering the results obtained and the many theoretical advantages of GnRH antagonists, ovarian stimulation with GnRH antagonists is an efficient treatment for both women with normal and high BMI.

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study

BackgroundAim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection.MethodsOne hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n = 50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment.ResultsTotal length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups.ConclusionsOur findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients.

Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial

To test whether metformin administration reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in infertile high-risk patients with polycystic ovary syndrome (PCOS) who have been treated with gonadotropins for IVF. Parallel, randomized, double-blind, placebo-controlled clinical trial. Academic departments, general hospital, and IVF centers. One hundred twenty patients with PCOS at high risk for OHSS. Gonadotropins ovarian stimulation for IVF and metformin (500 mg three times daily) or placebo tablets (three times daily). The primary end point of the current clinical trial was the rate of OHSS. Anthropometric and reproductive data were evaluated. The total OHSS and cancellation rates were significantly reduced in patients treated with metformin. The relative risk for OHSS was of 0.28 (95% confidence interval, 0.11-0.67). With metformin the stimulation length and the total amount of gonadotropins used were significantly increased, whereas the peak E(2) levels were significantly reduced. In patients with PCOS who are at high risk for OHSS and who have been stimulated with gonadotropins for IVF cycles, metformin reduces the risk of OHSS by modulating the ovarian response to the stimulation. REGISTRATION ID NUMBER FROM CLINICALTRIALS.GOV: NCT01233206.