Agonist Protocol Research Articles

The regulation of the follicular synchronization and sensitivity of rats with PCOS by AMH during prolonged pituitary downregulation

The modified prolonged gonadotropin-releasing hormone agonist (GnRH-a) protocol lessens the ovarian hyperstimulation syndrome (OHSS) effect and improves the clinical pregnancy rate of women with polycystic ovary syndrome (PCOS) compared with the standard long GnRH-a protocol. However, the molecular basis of this process needs to be elucidated. Sprague Dawley (SD) female rats with letrozole-induced PCOS were divided into GnRH-a and blank groups. Rats in the GnRH-a group were given triptorelin for 11 days, whereas those in blank group were given an equal volume of 0.9% NaCl. Meanwhile, the changes in estrus cycle, hormonal profile, ovary index, ovarian histopathology and body weight were measured. The expressions of anti-mullerian hormone (AMH), type II receptor of AMH (AMHRII), and FSH receptor (FSHR) were taken as the indicators of follicular sensitivity. Changes of follicular counting and differences in antral follicle diameter at each stage were evaluated. The number of follicles from primordial to antral stages increased during downregulation and the differences in antral follicle diameter were reduced in the GnRH-a group, whereas no significant difference was found in the blank group. The results of Western blotting and ELISA indicated that the level of AMH in ovarian total protein and serum had a similar dynamic change in the GnRH-a group. The results of immunohistochemistry showed that follicular AMH, AMHRII, and FSHR significantly decreased in the GnRH-a group. Prolonged GnRH-a protocol can improve synchronization and sensitivity of follicular development by balancing the expressions of AMH, AMHRII, and FSHR among follicles at all levels, thereby achieving better therapeutic effect.

Comparative study between agonist and antagonist protocols in PCOS patients undergoing ICSI: a cross-sectional study

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5–10% of women of reproductive age. The syndrome is surrounded by controversies regarding both its diagnosis and treatment. The introduction of long-acting GnRH agonists in the late 1980s revolutionized the approach to ovarian stimulation in assisted reproductive technologies by providing the means to downregulate endogenous pituitary gonadotropin secretion and thereby prevent a premature luteinizing hormone surge during exogenous gonadotropin stimulation. The relatively recent introduction of GnRH antagonists in clinical practice has provided another option for ovarian stimulation in IVF. The purpose of this study was to compare the efficacy of the fixed GnRH antagonist vs. GnRH agonist long protocol in patients with polycystic ovary syndrome treated by ICSI.ResultsThere is a statistically significant difference between both groups in view of the received dose of gonadotrophin (1901.7 ± 400.6 vs. 1789 ± 368 with p = .004) and duration of stimulation (11.3 ± 0.8 vs. 10.3 ± 1.1 with p = .017). There is no significant difference between both groups in view of pregnancy outcome (37% vs. 32% with p = .125). There is a significant difference between both groups in view of ovarian hyperstimulation syndrome (OHSS) incidence where the rates were 15%, 6%, and 1.5% vs. 4.5%, 2.5%, and .05% with p = 0.04 for mild, moderate, and severe, respectively, form of OHSS in group 1 and group 2.ConclusionThe antagonist protocol may be the preferred stimulation protocol for PCOS patients treated by ICSI in view of the reduction of OHSS incidence rates without compromising the pregnancy outcome.

A novel strategy of using corifollitropin alfa in the ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol in unselected patients: A patient-friendly alternative

ObjectiveTo compare the outcomes of in vitro fertilization (IVF) and fresh embryo transfer (ET) using corifollitropin alfa in ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol and GnRH antagonist protocol. Materials and methodsA total of 245 unselected patients undergoing IVF/fresh ET were enrolled between January 1 and December 31, 2017, including 135 treated with ultrashort GnRHa protocol and 110 treated with antagonist protocol. The primary outcomes were number of total injections and outpatient department (OPD) visits before ovulation triggering. The secondary outcomes were the duration of stimulation, dosage of additional gonadotropin for ovarian hyperstimulation, rates of pregnancy, clinical pregnancy, live birth, ovarian response, and ovarian hyperstimulation syndrome (OHSS) rate. ResultsPatients treated with ultrashort GnRHa required less additional gonadotropin, fewer total injections, but had better ovarian responses, including more oocytes retrieved, more metaphase II oocytes, and more blastocysts than those treated with antagonist did. A premature LH surge occurred only in six patients treated with antagonist protocol. The rates of pregnancy (37.0% vs. 43.6%), clinical pregnancy (25.2% vs. 34.6%), and live birth (19.3% vs. 30.0%) did not differ significantly between the two groups. The OHSS rate was similar in the two groups. ConclusionIn unselected patients using corifollitropin alfa, the ultrashort GnRHa protocol needed lower dose of additional gonadotropin and fewer injections but produced similar pregnancy outcomes than antagonist protocol did, suggesting that the ultrashort GnRHa protocol could be an alternative.

Impact of maternal ethnicity on pregnancy outcome in infertile women with polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is the most prevalent endocrine pathology seen among women of reproductive age. The objective of the study is to investigate the impact that ethnic background has on pregnancy outcomes, including live birth rates in infertile women with PCOS going through IVF compared to women without PCOS. Retrospective cohort study in an academic IVF center. This study used a coded REDCap data set of 486 women, 18-45 years of age who underwent IVF and embryo transfer between 1/1/2010 and 12/31/2015 at an academic IVF Center after IRB approval (IRB 2015-0623). Patients underwent their 1st IVF cycle following progestogen withdrawal (norethindrone acetate) using GnRH agonist or antagonist protocols with mixed gonadotropins and demographic data, including race and ethnicity was obtained. Data collected during the IVF process included peak estradiol, number of mature oocytes, fertilization rate, number of top quality embryos on Day 3 of development, number of embryos transferred, implantation rate, clinical pregnancy rate, live birth rate, clinical miscarriage rate, and ectopic pregnancy rate. In women, whose pregnancy resulted in a live birth, additional maternal and neonatal variables were collected, including estimated gestational age (EGA) at delivery, mode of delivery, and weight at birth. Using R analytics software, data was analyzed using logistic regression and linear models. For logistic regression, the estimated coefficient was the log-odds-ratio. A significant p value was considered <0.05. Of the 486 initial women, 360 women were included in the final analysis. Only women with known/reported ethnicity were included. Not Hispanic is the referent cohort for ethnicity and non-PCOS is the referent group when comparing PCOS status. There was no significant difference found for implantation rate (p=0.53) and pregnancy rate (p=0.99) when comparing women without PCOs with the women with PCOS. When taking into account the ethnicity factor in PCOS and the women who conceived and had a live birth, there was no significant difference between being Hispanic with PCOs and the referent non-Hispanic group. However, when evaluating women who started the IVF cycle, women with PCOS are less likely to have a pregnancy that leads to a live birth compared to women without PCOS (p=0.046). Being Hispanic by itself does not seem to affect live birth (p= 0.81). Hispanic women with PCOS have the same probability of having a vaginal delivery compared to the referent group (p=0.935). Women with PCOS are more likely to deliver ∼2 weeks earlier than non-PCOS patients (p=0.038). Being Hispanic and having PCOS did not affect the EGA at delivery (p= 0.83) or affected fetal weight compared to the referent group (p=0.58). This pilot study did not find a significant difference in most of the variables studied comparing Hispanic PCOS women with non-Hispanic women without PCOS. However, further studies with a larger number of subjects are needed to assess the impact of ethnicity and PCOS on IVF pregnancy outcomes.

Corifollitropin alfa in the ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol: a novel patient-friendly alternative

Corifollitropin alfa in the ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol: a novel patient-friendly alternative

Predictive factors for oocyte retrieval failure in treatment cycles with assisted reproductive technology: a retrospective cohort study using the nation-wide art registry of Japan

The purpose of this study was to evaluate the prognostic factors for oocyte retrieval failure in patients undergoing assisted reproductive technology (ART) treatment cycles. A retrospective cohort study. The present study was approved by the Ethical Committee on human subjects. The data analyzed in this study were part of the Japanese ART registry database, which was collected by the Japan Society of Obstetrics and Gynecology from 2010 to 2012. We analyzed the data of 464,480 fresh cycles with transvaginal oocyte aspiration. The cycles with oocyte retrieval failure and those with one or more oocytes retrieved were compared to determine predictive factors for oocyte retrieval failure using multivariate logistic regression analyses. The number of cycles with oocyte retrieval failure was 36,600 (7.9%). According to the multivariate analysis, age, cause of infertility, and controlled ovarian hyperstimulation (COH) were the independent prognostic factors for oocyte retrieval failure. The percentages of oocyte retrieval failure in the age groups of 29 years old and under, 30-34 years old, 35-39 years old, 40-44 years old, and over 45 years old were 3.2%, 4.2%, 5.9%, 10.2%, and 18.6%, respectively. The odds ratios of patients in their 30’s and 40’s were 1.7 and 4.0 times those of the patients in their 20’s, respectively. The percentages of oocyte retrieval failure that corresponded to infertility caused by a male factor, tubal factor, endometriosis, and unknown factors were 5.6%, 7.3%, 8.0%, and 9.2%, respectively. The odds ratios for oocyte retrieval failure in the tubal factor, endometriosis, and unknown groups were 1.3, 1.4, and 1.7 times those in the male factor group, respectively. The percentages of oocyte retrieval failure in the COH cases using aromatase inhibitor or clomiphene (AI+CC), GnRH agonist, and GnRH antagonist were 10%, 1.5%, and 3.5%, respectively. The odds ratios for oocyte retrieval failure in the GnRH antagonist and AI+CC protocols were 2.4 and 5.3 times those for the GnRH agonist protocol, respectively. The percentage of oocyte retrieval failure in the natural cycles was 21%. The predictive factors for oocyte retrieval failure might be related to a patient’s age, particular causes of infertility, and COH protocols. These results provide information that may be useful for counseling patients before ART treatments.

Effect of long GnRH Agonist, GnRH Antagonist and Microdose Flare-up Agonist protocols on IVF results in patients with diminished ovarian reserve

Amaç: Düşük over rezervi tanısıyla IVF programına alınan hastalarda uygulanan mikro doz flare up , GnRH antagonist ve long GnRH agonist gibi farklı protokollerin IVF başarısındaki etkinliğinin karşılaştırılması. Gereç ve yöntemler: Sağlık Bilimleri Üniversitesi Ankara Etlik Zübeyde Hanım Eğitim ve Araştırma Hastanesi IVF Kliniğine Ocak 2009 ve Mayıs 2019 tarihleri arasında başvuran ve düşük over reservi tanısı alan hastalar çalışmaya dahil edildi. 713 kadın kullanılan kontrollü ovarian stimulasyon protokellerine göre 3 gruba ayrıldı: Grup A(n=327) GnRH antagonist protokol, Grup B(n=184), long GnRH agonist protokol ve Grup C (n=202) mikrodoz flare-up protokol olarak belirlendi. Gruplar arasında ovarian stimulasyon karekteristikleri ve klinik gebelik sonuçları karşılaştırıldı. Bulgular:713 olgu çalışmaya dahil edildi. Long GnRH agonist protokol grubu, Grup A ve Grup C ile karşılaştırıldığında stimulasyon süresi anlamlı olarak daha uzun ve matur oosit sayısı daha fazla bulundu(p=0.001).Total gonadotropin dozu ve siklus iptal oranları grup C de anlamlı olarak yüksekti(p=0.001).Gruplar arasında toplanan oosit sayısı açısından anlamlı fark bulunmadı. Klinik gebelik oranları bakımından gruplar arasında anlamlı fark tespit edilmedi(p=0.337). Sonuç: Düşük over reservi olan kadınlarda tedavi süresi maliyeti azaltması nedeniyle , GnRH antagonist protokolü tedavi seçeneği olabilir.

The Significance of Endometrial Scratching for Clinical Pregnancy Rate in Long Agonist and Antagonist Protocols.

Background and Objectives: Assisted reproductive techniques today have helped many infertile couples achieve their desired pregnancy. However, unsuccessful implantation is usually the key failure in in vitro fertilization cycles. Many factors are now being studied to improve the implantation rate, one being endometrial artificial injury (endometrial scratching). The purpose of this study was to assess whether local endometrial artificial injury improved pregnancy rate, in long agonist and antagonist protocols. Materials and Methods: A retrospective analysis was carried out at the JSC Baltic American Clinic from January 1, 2016 to December 31, 2018. Women who were undergoing in vitro fertilization treatment were enrolled in the study. Medical data including demographic factors, menstrual history, and anamnesis of infertility were collected from medical records. Subjects were divided into intervention and control groups. The outcome of this study was clinical pregnancy rate (CPR). Results: A total of 137 women presenting with primary or secondary infertility were enrolled in the study. Clinical pregnancy was observed in 44/71 (61.9%) patients in the intervention group and 33/66 (50%) in the group without endometrial scratching (p value = 0.16). CPR in the intervention group was significantly higher in the patient group that had undergone ovarian stimulation with a long agonist protocol rather than the antagonist protocol (73.8% vs. 41.4%; p value = 0.006). In the multivariable logistic regression model, previously failed in vitro fertilization (IVF) (odds ratio (OR) = 0.07, 95% confidence interval (CI) 0.01–0.47), stimulation with the long agonist protocol (OR = 19.89, 95% CI 3.57–18.63), antagonist protocol (OR = 0.05, 95% CI 0.01–0.34), number of embryos (OR = 1.37, 95% CI 1.05–1.38), and number of blastocysts (OR = 2.96, 95% CI 1.43–8.36) remained important independent prognostic factors for clinical pregnancy. Conclusions: Our study findings indicate that randomized controlled studies are required to define patients for this procedure and to prove the effect and safety of local endometrial injury, before it is introduced to routine clinical practice.

Effects of oral contraceptive pretreatment on IVF outcomes in women following a GnRH agonist protocol.

Does oral contraceptive pretreatment impact IVF-embryo transfer cycle outcomes in women following the gonadotrophin-releasing hormone agonist (GnRHa) protocol? This retrospective study was designed to compare cycle outcomes after oral contraceptive pretreatment versus the standard protocol in women within the GnRHa long protocol or the GnRHa short protocol. A total of 2052 women undergoing their first IVF treatment with the GnRHa long protocol and 3557 women with the GnRHa short protocol between 2012 and 2017 were enrolled. No significant differences in the rates of clinical pregnancy (long protocol: 49.2% versus 46.7%; short protocol: 39.4% versus 38.0%) or live birth (long protocol: 44.3% versus 41.3%; short protocol: 32.8% versus 31.4%) after fresh embryo transfer were observed between the oral contraceptive group and the control group in either the long protocol or the short protocol. Oral contraceptive pretreatment has no effect on IVF outcomes in either the GnRHa long protocol or short protocol.

COMPARISON OF PREGNANCY RATE AMONG DIFFERENT IVF/ICSI PROTOCOLS IN WOMEN WITH PCOS.

Objective:To assess the pregnancy rate after using of different IVF/ICSI protocols in patients with PCOS. Study design: A total of 55 infertile women with Polycystic ovary syndrome undergoing controlled ovarian hyperstimulation for intracytoplasmic sperm injection cycle were prospectively recruited for this study in High Institute of Infertility Diagnosis and Assisted Reproductive Technology / AL-Nahrian University and Kamal AL-Samarai Hospital, center of fertility and IVF (Baghdad/Iraq) during the period from December 2015 to the end of April 2017.The fifty five PCOS women were divided into three groups: Twenty five (25) infertile women have had PCOS and young age undergone long Agonist protocol for ICSI cycle, Fifteen (15) infertile women have had PCOS who young age and have risk of OHSS (AMH > 6ng/ml or had previous history of hyper-response to ovarian stimulation protocol) undergone Antagonist protocol for ICSI and Fifteen (15) infertile women have had PCOS and age between 35-40 years old undergone short Agonist protocol for ICSI. In all patients B-HCG measure at day 14 after embryo transfer. Results:pregnancy rate was significantly higher in the PCOS patients underwent short agonist protocol (40%) compared to the PCOS patients underwent Antagonist protocol (20%) and to PCOS patients underwent long agonist protocol (16%) (P=0.0028). In this study, the percentage of pregnancy in PCOS group was (23.6%). Conclusion: It was concluded from the present study that the percentage of pregnancy was higher in polycystic ovary syndrome women more than 35 years old underwent short agonist protocol than in other ICSI/IVF protocols.

To Investigate the Cumulative Live Birth Rates Using GnRH Antagonist or Agonist Protocol for COS in ART Treatment

To Investigate the Cumulative Live Birth Rates Using GnRH Antagonist or Agonist Protocol for COS in ART Treatment

Evaluation of Ovarian Stimulation Initiated From the Late Follicular Phase Using Human Menopausal Gonadotropin Alone in Normal-Ovulatory Women for Treatment of Infertility: A Retrospective Cohort Study.

Objective: To investigate the feasibility of ovarian stimulation initiated in the late follicular phase using human menopausal gonadotropin (hMG) alone in ovulatory patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments by comparison with that of the short gonadotropin-releasing hormone agonist (GnRH-a) protocol in terms of ovarian response, embryological characteristics, and pregnancy outcomes following frozen-thawed embryo transfer (FET) cycles.Design: Retrospective cohort study.Setting: A university-affiliated tertiary hospital.Patients: 135 infertile women undergoing their first IVF/ICSI treatment with the freeze-all strategy.Interventions: In the study group, ovarian stimulation was initiated in the late follicular phase using hMG alone, with the confirmation of dominant follicular diameter ≥ 14 mm, while a short GnRH-a protocol was adopted in the control group. Oocyte maturation was induced by human chorionic gonadotropin in both groups. All good quality embryos were cryopreserved for later transfer.Main Outcome Measures: The primary outcome was the incidence of premature luteinizing hormone (LH) surge. Secondary outcomes were the number of mature oocytes retrieved, good-quality embryo rate per oocyte retrieved, and clinical pregnancy rate following FET cycles.Results: No premature LH surge was detected during ovarian stimulation in the study group. There was no statistically significant difference in the number of mature oocytes between the two groups (10 ± 5.6 in the study group vs. 8.51 ± 5.03 in the control group, P = 0.11). Good-quality embryo rate per oocyte retrieved did not differ between the two groups: 40.18% (313/779) vs. 36.67% (253/690), P = 0.167. Clinical pregnancy rate per transfer following FET was comparable between the two groups (61.33 vs. 52.5%, P = 0.267).Conclusions: Our study shows that ovarian stimulation initiated in the late follicular phase using hMG alone may be a feasible alternative for normal-ovulatory women undergoing IVF/ICSI treatment with the freeze-all strategy.

How does stress, depression and anxiety affect patients undergoing treatment?

To review latest findings about the impact of fertility care on emotional distress and effect of distress on treatment outcome. Treatment failure and long agonist protocols are associated with increased emotional distress during treatment. Screening tools can be used to identify men and women at risk of emotional maladjustment at the start of fertility treatment and people unlikely to need emotional support during or after treatment. There are inconclusive results about the association between emotional distress and outcome of fertility treatment. Systematic review of studies evaluating the effect of psychological and educational interventions on anxiety, depression and live birth (or ongoing pregnancy) are uninformative because of clinical heterogeneity and risk of bias. ART is emotionally demanding, patients that adapt more poorly can be identified in advance. Fertility staff should follow good practice guidelines to provide patients with support during treatment.

Clinical pregnancy following GnRH agonist administration in the luteal phase of fresh or frozen assisted reproductive technology (ART) cycles: Systematic review and meta-analysis.

Objective(s)To study if the GnRH agonist administration in luteal phase improves clinical pregnancy rate of fresh and frozen embryo transfer. Also, this meta-analysis compares the treatment effect of luteal GnRH agonist administration between long agonist and antagonist protocols of fresh cycles, and between two types of treatment: fresh and frozen embryo transfers.Study designSystematic review and meta-analysis (registration number CRD42017059152)ResultsFor the overall 20 studies (5497 patients), clinical pregnancy rate significantly increased in group of GnRH agonist administration compared to control group (RR 1.24, 95% CI 1.14–1.34, p < 0.0001). Regarding the treatment effect of luteal GnRH agonist administration between long agonist and antagonist protocol fresh cycles, no significant difference was observed (RR = 1.28, 95% CI 0.98–1.67, p = 0.07). Also, in comparison between fresh and frozen embryo transfer, similar effect of GnRH agonist administration was found (RR = 0.93, 95% CI 0.74–1.16, p = 0.49).Conclusion(s)There is evidence that GnRH agonist administration in luteal phase improve clinical pregnancy rate in both fresh and frozen cycles. Within fresh cycles, no significant difference of clinical pregnancy rate is found between two protocols. In frozen cycles, the effect of GnRH agonist administration in enhancing clinical pregnancy rate is similar to fresh cycles.

Controlled ovarian stimulation protocols in endometriosis patients: with antagonist or agonist?

To compare laboratory and clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) in patients with endometriosis using antagonist protocol, long agonist protocol or prolonged agonist protocol. Totally 313 patients with endometriosis were recruited in Reproductive Centers of the Second Affiliated Hospital of Zhejiang University School of Medicine,Jiaxing Women and Children's Hospital,and Ningbo Women and Children's Hospital from April 2017 to October 2018, including 81 patients treated with antagonist protocol (antagonist group), 148 treated with long agonist protocol (long agonist group) and 84 treated with prolonged agonist protocol (prolonged agonist group). The clinical and laboratory data of the patients were retrospectively analyzed to investigate the effect of ovarian stimulation protocols on the IVF-ET outcomes of patients with endometriosis. The average age in the antagonist group patients was significantly higher than those in the other two groups (all P<0.05),and anti-mullerian hormone (AMH) level and antral follicle numbers were significantly lower than those in the other two groups (all P<0.01). The numbers of average retrieved oocyte, fertilized oocyte and available embryo in the antagonist group were significantly lower than those in the long agonist group (all P<0.05), but were similar with those in the prolonged agonist group (all P>0.05). Fertilization rate and available embryo rate were comparable among the three groups (all P>0.05). Considering analysis per cycle with embryo transfer, the human chorionic gonadotrophin (HCG) positive rate, clinical pregnancy rate and total implantation rate showed no significant difference among the three groups (all P>0.05). The implantation rate after fresh embryo transfer in the antagonist group was lower than that in the long agonist group (P<0.05), but was similar with that in the prolonged agonist group (P>0.05). While the implantation rate of freeze-thaw embryo transfer showed a higher trend in the antagonist group, but there was no significant difference (P>0.05). The patients were further divided into diminished and normal ovarian reserve subgroups, the per cycle with embryo transfer, the HCG positive rate, clinical pregnancy rate and total implantation rate still showed no significant difference between two subgroups (all P>0.05), no matter in which ovarian stimulation protocol groups. Besides, in women with diminished ovarian reserve, the available embryo rate in antagonist group was significantly higher than that in the long agonist group (P<0.05). The amount and duration of Gn application in antagonist group were significantly lower than those in long and prolonged agonist groups (all P<0.05). Patients with endometriosis who used the antagonist protocol in IVF procedure could reduce the cost and time of Gn treatment, when combined with frozen-embryo transfer strategy the antagonist protocol has comparable clinical pregnancy outcome with long or prolonged agonist protocol, especially in those with diminished ovarian reserve, the higher available embryo rate can be achieved.

A predictive formula for selecting individual FSH starting dose based on ovarian reserve markers in IVF/ICSI cycles.

Although exogenous follicle-stimulating hormone (FSH) has been used for decades and millions of cycles have been performed worldwide until now, criteria for selecting the proper FSH starting dose have not been clearly identified. The aim of this study was to elaborate a formula based on markers of ovarian reserve for the calculation of the appropriate starting dose of FSH. A total of 931 patients underwent in vitro fertilization (IVF) treatment using long GnRH agonist protocol was retrospectively identified and reviewed. 673 cases of them with a normal ovarian response (4-14 retrieved oocytes) were used to analysis the predictive formula. All follicles 4-7mm in diameter were counted in the same day of blood sample in both ovaries using transvaginal ultrasound scan. The modified protocol of each patient was recorded and analyzed in the same center. In another center were the numbers of retrieved oocytes of 750 validated patients recorded and analyzed. A formula model based on age, AMH, and antral follicle count (AFC) was able to accurately predict the ovarian sensitivity and accounted for 57.2% of the variability of ovarian response to FSH. When tested in the same total population used to elaborate the model it predicts a high 46.88% rate of step-down protocol in higher-starting FSH dose group and about 57.92% of patients had their dose step-up modified in lower-starting FSH dose group during their treatment, respectively. And when tested in different population from another center used to elaborate the model it predicts a high 64.40% rate of ≥ 15 retrieved oocytes in higher-starting FSH dose group and about 22.50% of patients had ≤ 7 retrieved oocytes in lower-starting FSH dose group during their treatment, respectively. In the present study we demonstrated that the individualized FSH starting dose may be calculated on the basis of a woman's age, AMH and AFC. The formula model might be a useful, immediate, and easily applicable tool for clinicians to predict the tailored starting dose of FSH during their daily clinical practice.

Comparison of the Microdose Flare Up GnRH Agonist and Antagonist Protocol in Assisted Reproduction with Poor Ovarian Response during Controlled Ovarian Stimulation Cycles

Background: Poor ovarian response presents a significant challenge in artificial reproductive treatment (ART). Poor responders are estimated to comprise approximately 9- 24% of IVF cycles patients. Recently, the development of protocol offered another approach for ovarian stimulation by blocking the pituitary receptors. There is evidence that application of protocol decreases the duration of ovulatory stimulus and reduce incidence of ovarian hyperstimulation syndrome (OHSS). Objectives: The aim of the current study was to evaluate the effect of the protocol to the microdose flare up agonist protocol for poor ovarian responders undergoing IVF/ICSl treatment. Patients and Methods: A total of sixty patients of IVF/ICSI assigned to be poor responders were randomized into two groups; group 1 Thirty patients received fixed protocol and group 2 thirty patients received a microdose flare up agonist protocol. Patients characteristics and treatment outcomes were statistically compared between groups. Results: Duration of stimulation was highly significantly lower in the group than that of the microdose flare up one (antagonist 8.60±1.63 versus microdose flare up 12.06±2.86; p=0.001). Number of ampoules of HMG was highly significantly lower in the group than that of the micro dose flare up agonist one (antagonist 23.53±7.33 versus micro dose agonist 71.97±9.35; p=0. 001). The number of oocytes retrieved in the group was not different from microdose flare agonist group (5.14±2.45 vs. 5.11±1.29; p=0.953), and the number of embryos transferred was similar in both groups (2.03±0.08 vs. 2.09 ± 1.05; p=0.674). No significant differences in pregnancy rates were reported. Conclusion: we offer using the GnRH antagonist as a patient friendly protocol in ART with poor ovarian response with Immediate mode of action, similar pregnancy rate, time saving, less duration of stimulation and number of ampoules for stimulation than microdose flare up protocol.

The Role of Transdermal Testosterone Patch Over Pregnancy Rates in Poor Ovarian Responders Undergoing ICSI Cycles

Background: poor responder management in IVF represents a critical dispute for fertility specialists. Meanwhile, there is a lack of evidence to support the use of any particular intervention to improve treatment outcomes in poor responders because of the small sample size and the heterogeneity between the trials on the definition of poor ovarian responders (POR). Objective: the aim of this study was to evaluate the role of transdermal testosterone on the probability of pregnancy achievement in poor responders undergoing ICSI trials. Thus, the number of oocytes, pregnancy rates (clinical and live birth) and HMG dose and duration were compared between both trials. Patients and Methods: This single-centre, randomized controlled trial was conducted from August 2016 to August 2017. A total of 61 poor responder patients with previous failed trial underwent their second ICSI trial. The patients received ovarian stimulation using a short GnRH agonist protocol in both trials with transdermal testosterone patches being used in the second trial starting five days prior to HMG. Results: The oocytes recruitment and the pregnancy rates were higher after testosterone pretreatment in the second trial, however, the difference between the previous and the second trial didn’t reach the statistical significance. Conclusion: Testosterone patches effect on oocyte number and pregnancy rates appears to be minimal for poor responders. However, further trials are needed to prove the study’s conclusion in the future.

The Role of Transdermal Testosterone Patch Over Pregnancy Rates in Poor Ovarian Responders Undergoing ICSI Cycles

Background: poor responder management in IVF represents a critical dispute for fertility specialists. Meanwhile, there is a lack of evidence to support the use of any particular intervention to improve treatment outcomes in poor responders because of the small sample size and the heterogeneity between the trials on the definition of poor ovarian responders (POR). Objective: the aim of this study was to evaluate the role of transdermal testosterone on the probability of pregnancy achievement in poor responders undergoing ICSI trials. Thus, the number of oocytes, pregnancy rates (clinical and live birth) and HMG dose and duration were compared between both trials. Patients and Methods: This single-centre, randomized controlled trial was conducted from August 2016 to August 2017. A total of 61 poor responder patients with previous failed trial underwent their second ICSI trial. The patients received ovarian stimulation using a short GnRH agonist protocol in both trials with transdermal testosterone patches being used in the second trial starting five days prior to HMG. Results: The oocytes recruitment and the pregnancy rates were higher after testosterone pretreatment in the second trial, however, the difference between the previous and the second trial didn’t reach the statistical significance. Conclusion: Testosterone patches effect on oocyte number and pregnancy rates appears to be minimal for poor responders. However, further trials are needed to prove the study’s conclusion in the future.

Clinical outcomes following long GnRHa ovarian stimulation with highly purified human menopausal gonadotropin plus rFSH or rFSH in patients undergoing in vitro fertilization-embryo transfer: a multi-center randomized controlled trial.

This clinical trial aimed to compare the clinical efficacy of highly purified human menopausal gonadotropin (HP-HMG) plus recombinant human follicle-stimulating hormone (rFSH) versus rFSH alone on controlled ovarian stimulation (COS) in vitro fertilization-embryo transfer (IVF-ET). A total of 610 women underwent long gonadotropin-releasing hormone (GnRH) agonist protocol for IVF treatment. The subjects were randomized into 2 groups: HP-HMG + rFSH group (n=305) and rFSH group (n=305). The main outcome was the progesterone (P) level on the day of HCG injection. There was no significant difference in terms of the demographic and baseline characters between the two groups. In rFSH group, the P level on the day of HCG trigger were significantly higher than that of HP-HMG+rFSH group (4.3±2.2 vs. 3.8±1.7 nmol/L, P<0.001). The fertilization rate in rFSH group was significantly lower than that of HP-HMG + rFSH group (69.2% vs. 73.9%, P<0.001). Simultaneously, the percentage of cycles with fresh embryo transfer in rFSH group was also significantly lower than that of HP-HMG + rFSH group (49.6% vs. 57.5%, P=0.007). However, there was no difference in terms of cleavage rate, implantation rate, clinical pregnancy rate and ovarian hyperstimulation syndrome (OHSS) rate between two groups. The use of combined HP-HMG with FSH may be superior to rFSH alone in stimulating the ovary in normal responders undergoing IVF treatment. Furthermore, the further prospective studies with large sample are still needed to confirm the study.