Agonist Protocol Research Articles

Oxidative stress status in severe OHSS patients who underwent long agonist protocol intracytoplasmic sperm injection cycles

Oxidative stress status in severe OHSS patients who underwent long agonist protocol intracytoplasmic sperm injection cycles

Role of follicular fluid leptin hormone in women with polycystic ovarian syndrome in assisted reproductive technology

Background/aim Granulosa cells have the capacity for producing and storing leptin, proposing that this hormone is locally involved in regulating follicular growth. The aim of this work was to evaluate the levels of follicular fluid (FF) leptin hormone and its correlation with pregnancy outcome in polycystic ovarian syndrome (PCOS) cases undergoing intracytoplasmic sperm injection cycles using both long gonadotrophin-producing hormone (GnRH) agonist and fixed GnRH antagonist protocols. Patients and methods This was a randomized controlled trial that included 100 patients with PCOS from the reproductive unit of Alexandria University Hospitals, Egypt, who were randomly allocated in two groups (50 patients ech): group 1 included patients with PCOS undergoing long GnRH agonist protocol, and group 2 included patients with PCOS undergoing fixed GnRH antagonist protocol. Anthropometric measurements were done, in addition to assays of FF leptin, serum Anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, and progesterone levels, assessed by enzyme-linked immunosorbent assay techniques. Results FF leptin had a highly significant increase in nonpregnant patients when compared with pregnant patients in both groups. In addition, there were significant increases in BMI and weight, whereas insingnificant difference regarding height between nonagonist and antagonist groups. Conclusion Leptin can negatively influence in-vitro fertilizations outcomes via weakening several stages of endometrial and ovarian physiology. The exact function of leptin in the poorer outcomes commonly found in obese cases throughout controlled ovarian stimulation needs to be explained, and there is a need to assess the correlation between free bioactive leptin and in-vitro fertilizations cycle parameters.

The Follicular Output Rate (FORT) as a method to evaluate transdermal testosterone efficacy in poor responders.

Objective:Follicular Output Rate (FORT) is an efficient quantitative and qualitative marker of ovarian responsiveness to gonadotropins. Transdermal testosterone (TT) has been used as adjuvant therapy to gonadotrophins in order to improve ovarian response in poor responders (PR). The aim of this study was to analyze whether TT can improve follicular sensitivity to gonadotropins using FORT.Methods:This retrospective study, held in a tertiary-care university hospital included 90 PR patients, according to the Bologna criteria. Patients in Group 1 (n = 46) received transdermal application of testosterone preceding gonadotrophin ovarian stimulation under pituitary suppression. In Group 2 (n = 44) ovarian stimulation was carried out with high-dose gonadotrophin in association with minidose GnRH agonist protocol. We analyzed ovarian stimulation parameters and IVF outcomes. We determined antral follicle count (AFC) (3-8 mm) before ovarian stimulation, pre-ovulatory follicle count (PFC) (16-22 mm) and the day of hCG administration. We calculated the FORT using the PFCx100/AFC ratio.Results:Baseline characteristics and ovarian reserve parameters were similar in both groups. FORT and oocytes retrieved were significantly higher in group 1 vs group 2. There were no significant differences in pregnancy rates. In group 1 there was a significant correlation between FORT and AFC.Conclusions:This study suggests that the potential beneficial mechanism of TT in poor responder patients may be based on increasing the antral follicle sensitivity to gonadotrophin. FORT is an excellent tool to demonstrate this.

Comparative study between ovarian response prediction index versus anti-Müllerian hormone, antral follicular count as predictors of ovarian response in women undergoing IVF/ICSI cycles

Aim:This study aimed to compare individual predictors as AMH, AFC versus the ovarian response prediction index in determining the ovarian response to controlled ovarian stimulationMaterials and Methods: A prospective cohort study conducted on 84 infertile couples candidate for Intracytoplasmic sperm injection (ICSI) for the first time using either long agonist or antagonist protocol according to clinical evaluation. Participants were classified according to the number of MII oocytes into poor response with 3 or less oocytes and normal responders with 4 or more oocytes.Results: The study showed that women with poor response were statistically older than those with normal ovarian response (33.1±5.9 vs. 29.8±5.4, respectively). The number of cumulus (12.1±5.2 vs. 2.5±1.5), MII oocytes (7.8±3.6 vs. 2±0.8), grade A embryos (3±0.8 vs. 1.4±0.9) and total number of embryos (3.8±2.2 vs. 1.7±0.7) were significantly higher in normal responders. ORPI has the highest accuracy in predicting ovarian response (88%) when compared to AMH (83%) and AFC (86%).Conclusion: AMH, AFC and ORPI are good predictive of the ovarian response and help in choosing the protocol and gonadotropin dose of induction and prediction of OHSS

Live-Birth Outcomes and Congenital Malformations After Progestin-Primed Ovarian Stimulation in Maternal Endometriosis.

PurposeIn patients who had advanced endometriosis, we use different protocols including GnRH agonist, GnRH antagonist and progestin-primed ovarian stimulation (PPOS) protocols to assess live-birth congenital malformations delivered after in vitro fertilization (IVF) and vitrified embryo transfer cycles.MethodsA retrospective cohort study is conducted by us. It includes 1495 live-born infants in maternal endometriosis. From January 2010 to January 2017, we brought into infants who underwent either gonadotropin-releasing hormone agonist long protocol, gonadotropin-releasing hormone antagonist protocol or PPOS. We chose neonatal outcomes and congenital malformations as our major measures.ResultsNeonatal outcomes, as well as congenital malformations, were considered as the main measures, and gestational age, birth weight, birth length, multiple births and early neonatal death are included. All groups were comparable. The GnRH antagonist group (1.41%) and the GnRH antagonist protocol group (1.8%) had the same incidence of live-birth defects as the PPOS groups (1.33%) were similar. There were no apparent differences when it came to congenital malformations among the three groups. Multivariate logistic regression showed that infertility-time factors as well as multiple births combined to add the risk of congenital malformations; the adjusted odds were 1.143 (95% confidence interval [CI]: 0.988–1.323) and 3.253 (95% CI: 1.359–7.788). Besides, no association was found among various ovarian stimulations as well as congenital birth defect programs, maternal age, body mass index, parity or infant sex.ConclusionThis study suggests that, in contrast to conventional ovarian stimulation, PPOS neither has any effect on neonatal outcomes in IVF adverse effects nor does it elevate the rate of congenital malformations in late endometriosis. However, randomized controlled trials of the long-term outcomes of children born after PPOS protocols for maternal endometriosis are needed and the follow-up studies were conducted to confirm this result.

The effects of luteinising hormone gene polymorphism on the outcomes of in vitro fertilisation and embryo transfer

Trp8Arg polymorphism of the LH beta gene has decreased bioactivity in vivo and previous studies showed conflicting data on the effect of LH beta gene polymorphism on the IVF outcome. In this study, 591 IVF patients were recruited. Patients with the variant allele(s) were the carrier group. In GnRH antagonist cycles, the clinical pregnancy rate was significantly lower in the carrier group (18.9%) than in the noncarrier group (37.1%). In long GnRH agonist cycles, the clinical pregnancy rate was comparable between both groups. To clarify the effect of COH protocols, IVF outcomes in the GnRH antagonist and long GnRH agonist protocol groups in carriers were analysed. Among carriers, the clinical pregnancy rate was significantly lower in the GnRH antagonist protocol group (18.9%) than in the long GnRH agonist protocol group (45.2%). Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future. Impact Statement What is already known on this subject? Trp8Arg polymorphism of the LH beta gene is known to have decreased bioactivity in vivo. Previous studies have demonstrated hypo-sensitivity in the patients with the variant LH beta protein, while other study showed similar carrier frequency between the poor and the normal response group. What the results of this study add? The variant LH beta gene was associated with a lower clinical pregnancy rate in GnRH antagonist cycles but not in long GnRH agonist cycles. What the implications are of these findings for clinical practice and/or further research? Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.

Progestins for pituitary suppression during ovarian stimulation for ART: a comprehensive and systematic review including meta-analyses.

Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However, early endometrial exposure to progestin precludes a fresh embryo transfer (ET), but the advent of vitrification and increasing number of oocyte cryopreservation cycles allow more opportunities for using progestins for pituitary suppression. This review summarizes: the mechanism of pituitary suppression by progestins; the effectiveness of progestins when compared with GnRH analogues and with each other; the effect of progestins on oocyte and embryo developmental potential and euploidy status; and the cost-effectiveness aspects of progestin primed stimulation. Future research priorities are also identified. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, the Web of Science and Scopus were screened with a combination of keywords related to ART, progesterone, GnRH analogue and ovarian stimulation, in various combinations. The search period was from the date of inception of each database until 1 April 2020. Only full text papers published in English were included. Overall, the duration of stimulation, gonadotrophin consumption and oocyte yield were similar with progestins and GnRH analogues. However, sensitivity analyses suggested that progestins were associated with significantly lower gonadotrophin consumption than the long GnRH agonist protocol (mean difference (MD) = -648, 95% CI = -746 to -550 IU) and significantly higher gonadotrophin consumption than the short GnRH agonist protocol (MD = 433, 95% CI = 311 to 555 IU). Overall, live birth, ongoing and clinical pregnancy rates per ET were similar with progestins and GnRH analogues. However, when progestins were compared with GnRH agonists, sensitivity analyses including women with polycystic ovary syndrome (risk ratio (RR) = 1.27, 95% CI = 1.06 to 1.53) and short GnRH agonist protocols (RR = 1.14, 95% CI = 1.02 to 1.28) showed significantly higher clinical pregnancy rates with progestins. However, the quality of evidence is low. Studies comparing medroxyprogesterone acetate, dydrogesterone and micronized progesterone suggested similar ovarian response and pregnancy outcomes. The euploidy status of embryos from progestin primed cycles was similar to that of embryos from conventional stimulation cycles. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. Despite the lower cost of progestins than GnRH analogues, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase cost per live birth with progestins as compared to an ART cycle culminating in a fresh ET. Progestins can present an effective option for women who do not contemplate a fresh ET, e.g. fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles.

Endometrioma ethanol sclerotherapy could increase IVF live birth rate in women with moderate-severe endometriosis.

To examine the impact of ethanol sclerotherapy (EST) for endometrioma on in vitro fertilization (IVF) cumulative live birth rates (CLBR) in women with moderate-severe endometriosis. This retrospective cohort study included women with moderate-severe endometriosis (revised American Fertility Society stage III-IV) and endometrioma who underwent IVF with the ultra-long agonist protocol. We compared two groups: women undergoing EST for endometrioma before IVF (EST group), and women whose endometrioma was left in situ during IVF (No-EST group). The primary outcome was the CLBR per IVF cycle, including fresh and frozen embryo transfers. The secondary endpoints included the complication rate, number of mature oocytes retrieved, clinical pregnancy rate and pregnancy loss rate. Seventy-four women were included in the study, with 37 in the EST group and 37 in the No-EST group, representing 67 and 69 IVF cycles, respectively. The population and cycle characteristics were comparable between the two groups, especially the ovarian response to stimulation. The CLBR was significantly increased in the EST group compared to the No-EST group (31.3% vs. 14.5%, p = 0.03). The clinical and biochemical pregnancy rates were significantly increased in the EST group (37.3% vs. 15.9%, p = 0.01 and 43.3% vs. 23.2%, p = 0.01, respectively). Multivariate analysis revealed a significantly increased chance of live birth in women exposed to EST before IVF with an adjusted OR of 2.68 (95% confidence interval, CI: 1.13-6.36, p = 0.02). In the EST group, we reported one major complication Clavien and Dindo classification grade III, complication involving an ovarian abscess that required a laparoscopic drainage. EST is an interesting technique to improve IVF success rates in women with moderate-severe endometriosis. EST could be discussed before IVF in infertile women.

Degenerated oocyte in the cohort adversely affects IVF outcome

The presence of Degenerated Oocyte (DEG) was mostly described after intracytoplasmic sperm injection (ICSI), with fewer reports on DEG at the time of ovum pick-up (OPU). This study aims to assess morphokinetics of embryos cultured in a time-lapse incubator and compare cohorts with and without DEG at OPU. In a retrospective cohort study from January 1, 2016 until September 31, 2017 a total of 399 IVF/ICSI cycles and 2980 embryos were evaluated. In 81 of 399 cycles at least one DEG oocyte was observed at the time of OPU. The remaining 318 cycles with no DEG oocyte were compared as a control group. In the DEG group, significantly more oocytes were collected per patient (12.9 ± 7.2 vs. 10.1 ± 6.1. P < 0.001). Fertilization rate, pregnancy and clinical pregnancy rates were comparable between the two groups, however, the morphokinetics and developmental scores of the embryos were significantly worse in the DEG group, (KID 3.4 ± 1.6 vs. 3.2 ± 1.6 P = 0.002 and ESHRE 1.5 ± 1.1 vs. 1.4 ± 1.0 P = 0.046). Significantly more patients achieved top-quality embryos in the NON DEG group (58.8% vs. 53.0%, P = 0.03), however, comparable delivery rate was achieved in both groups. In the DEG group, the frequency of DEG oocyte per cycle was negatively correlated with pregnancy rate. GnRH agonist protocol and the 17-20G needle used for OPU were significant predictors for the presence of DEG oocyte at OPU. In conclusions DEG oocyte may negatively affect IVF outcome, however, younger patients, and significantly more oocytes collected in the DEG group compensate for the IVF results.

Does the Time of Starting Progesterone Luteal Support Affect Embryo Transfer in Long Agonist Protocol Downregulated ICSI Cycles? A Randomized Controlled Trial.

The aim of this study was to compare the effects of starting progesterone (P4) luteal support (LS) on day of egg retrieval (ER) or day of embryo transfer (ET) on the ratio of difficult ET and cycle outcome. This was a RCT ( ClinicalTrials.gov Identifier: NCT03040830) carried out at Mansoura Integrated Fertility Center (MIFC), Mansoura, Egypt, from November 2015 to January 2017. A total of 171 eligible long agonist ICSI cases were randomly allocated on day of ER into group A (86) starting LS as daily IM 100mg P4 on day of ER and group B (85) starting P4-LS on day of ET. Difficult ET was defined as blood on ET catheter and/or sounding or dilating the cervix. Primary outcome was the overall ratio of difficult ET and ratios on day 3 and 5 ET. Secondary outcome was the ongoing pregnancy rate (OPR) and implantation rate (IR). The results are presented as % for groups A and B respectively: overall difficult ET (44.1, 24.7) (p = 0.009); day 3 difficult ET (23.2, 24.4) (p = 0.45); day 5 difficult ET (62.7, 25.6) (p = 0.001); overall OPR (38.3, 44.7) (p = 0.43); day 3 ET OPR (41.8, 33.3) (p = 0.51); day 5 ET OPR (34.8, 57.5) (p = 0.048); overall IR (20.0, 22.5) (p = 0.62); day 3 ET IR (17.8, 13.4) (p = 0.44); day 5 ET IR (22, 34.1) (p = 0.09). In conclusion, starting P4 luteal support on egg retrieval day is associated with significantly higher ratio of difficult embryo transfer and lower ongoing pregnancy rate and tendency to lower IR in day 5 ET, so starting P4-LS on day of ET is recommended.

Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals

Research questionWhat are the risk factors affecting the incidences of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and severe hemoperitoneum in assisted reproductive technology (ART) treatment cycles? DesignA retrospective cohort study was conducted on 1,435,108 oocyte retrieval cycles among Japanese ART registry data between 2007 and 2015. The study included 11,378 cycles with moderate-to-severe OHSS, 1182 cycles with severe hemoperitoneum, including 27 cycles with both conditions, and 1,422,575 cycles without moderate-to-severe OHSS and severe hemoperitoneum. ResultsThe incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08%, respectively, and decreased by 0.57-fold and 0.29-fold from 2007 to 2015, respectively. In cycles with OHSS and cycles with hemoperitoneum women were younger (odds ratios [OR] 0.91 and 0.95, respectively) and had more retrieved oocytes (OR 1.09 and 1.01, respectively) compared with cycles without both complications. The use of a gonadotrophin-releasing hormone (GnRH) agonist protocol for ovarian stimulation was the highest risk factor in cycles with OHSS and hemoperitoneum (OR 1.83 and 1.24, respectively), followed by GnRH antagonist protocol (reference), gonadotrophin with or without oral medicine (OR 0.45 and 0.56, respectively) and natural or oral medicine (OR 0.02 and 0.19, respectively). In fresh embryo transfer, clinical pregnancy was associated with an increased risk of OHSS and hemoperitoneum (OR 1.19 and 2.34, respectively). ConclusionsThe highest risk factors affecting OHSS and hemoperitoneum were the use of a GnRH agonist protocol and clinical pregnancy following fresh embryo transfer. The incidences of OHSS and hemoperitoneum have decreased yearly with a reduction of GnRH agonist use and fresh embryo transfer.

FOLLICULAR-PHASE SINGLE-DOSE GnRH AGONIST PROTOCOL VS GnRH ANTAGONIST PROTOCOL IN PATIENTS WITH REPEATED IVF FAILURE

To compare the clinical outcomes between follicular-phase single-dose gonadotropin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol in patients with repeated IVF failure. Retrospective analysis. The IVF cycles conducted on 764 patients with repeated IVF failure (No. of previous failed IVF cycle>=2) and normal ovarian reserve (AMH >1.1ng/ml) from Jun. 2017 to Dec. 2019 were included in this retrospective cohort study. The follicular-phase single-dose GnRH agonist protocol, in which 3.75 mg Triptorelin was administrated on cycle day 2 and exogenous gonadotropin (Gn) was initiated 4 weeks later, was applied in 303 patients and GnRH antagonist protocol utilized in the remaining 461 patients. The clinical outcomes, including stimulation duration, total dose of exogenous Gn, No. of oocytes retrieved, No. of transferrable embryos, clinical pregnancy rate and miscarriage rate between the two groups were compared respectively. P<0.05 was considered as statistical significance. No significant difference was observed in basic characteristics between two groups. Comparing with the antagonist group, both the stimulation duration and the total Gn dose were significantly longer and higher in the agonist group. More oocytes and transferrable embryos were obtained, and the clinical pregnancy rate per fresh embryo transfer cycle was significantly higher in the agonist group. The basic and cycle characteristics were listed in the following table.Tabled 1GnRH agonist protocol (n=303)GnRH antagonist protocol (n=461)P valueAge (y)33.61±3.5833.95±3.940.231BMI (Kg/m2)22.20±5.4922.03±2.940.186Infertility duration (y)5.67±3.265.36±3.310.209AMH (ng/ml)3.29±2.083.39±3.181.000No. of previous IVF cycles2.62±1.042.62±1.330.952Gn initiation dose (IU)235.07±58.80229.00±59.360.164Stimulation duration (d)11.02±1.858.49±1.45<0.01Dose of Gn (IU)2633.45±783.821937.08±586.31<0.01No. of oocytes retrieved12.12±5.959.79±6.44<0.01No. of transferrable embryos4.24±3.503.57±3.23<0.01No. of good-quality embryos3.30±3.122.82±2.960.03No. of embryos transferred1.79±0.511.84±0.44<0.01No. of cycles with fresh embryo transfer181197Clinical pregnancy rate (%)53.6034.01<0.01Miscarriage rate (%)20.6214.930.354 Open table in a new tab In patients with repeated IVF failure, follicular-phase single-dose GnRH agonist protocol resulted in a significantly higher clinical pregnancy rate than antagonist treatment, implying that single-dose GnRH agonist treatment may offer additional benefits for this specific group of patients.

PREDICTING PROBABILITY OF CUMULATIVE LIVE BIRTH BASED ON BOTH BASELINE INFORMATION AND PROTOCOLS OF CONTROLLED OVARIAN STIMULATION

To develop a prediction model for the probability of cumulative live birth from one initiated assisted reproductive technology (ART) cycle based on couples’ baseline characteristics and controlled ovarian stimulation (COS) protocols. Therefore, we sought to create a clinical prediction model for counseling and COS protocol selection. A retrospective cohort study. From Jan 2012 to Mar 2016, all women at age of 19-39 years old with at least 5 antral follicle count (AFC) underwent just one complete ART cycle with long GnRH-agonist, depot GnRH-agonist, modified long GnRH agonist and GnRH-antagonist protocols in Chengdu Xi’nan Gynecology Hospital were included, and followed up to Mar 2018. Couples with chromosome abnormality were excluded. Cumulative live birth was defined as first live birth resulting from one initiated ART cycle, including cycles in which fresh and/or frozen embryos were transferred, until one delivery with a live birth occurs or until all embryos are used, whichever occurs first. A multivariate stepwise logistic regression model was used to predict the probability of cumulative live birth. The accuracy of the model was then tested using a receiver operating characteristic curve (ROC). 6862 patients with 6862 complete ART cycle were enrolled with a 72.89% overall cumulative live birth rate (CLBR), namely 5002 cycles cumulatively had live birth. Predictors in the model were female’s age (-0.07, 95% CI:-0.09∼-0.05, P<0.001), height (0.06, 95% CI:0.05∼0.08, P<0.001), weight (-0.01, 95% CI:-0.02∼0.00 , P=0.005), duration of infertility (-0.06, 95% CI:-0.08∼-0.04 , P<0.001), number of previous ART cycle (-0.60, 95% CI:-0.79∼-0.41 , P<0.001), basal AFC (0.08, 95% CI:0.07∼0.09, P<0.001), basal FSH (-0.09, 95% CI:-0.12∼-0.06, P<0.001) and COS protocols [long GnRH-agonist (reference category), depot GnRH-agonist (-0.08, 95% CI:-0.64∼0.48, P=0.785), modified long GnRH agonist (-0.69, 95% CI:-0.96∼-0.43 , P<0.001), GnRH-antagonist protocols (-0.12, 95% CI:-0.71∼0.47, P=0.696)]. The area under the curve (AUC) for ROC was 0.708. This model provides a scientific predicting method for probability of cumulative live birth, thus help doctors give patients more accurate counseling and select more suitable COS protocol.

COMPARISON OF CONTROLLED OVARY STIMULATION PROTOCOLS FOR IN VITRO FERTILISATION: A META-ANALYSIS

The purpose present of meta-analysis is to compare the effectiveness of different types of GnRH agonist (GnRH-a) protocols (long-acting follicular, long-acting luteal and short-acting luteal protocols) and GnRH antagonist (GnRH-ant) protocol for IVF.

IS Three D power Doppler of the endometrial and sub endometrial regions effective in predicting endometrial implantation? Prospective cohort study

Objective: This study aimed to evaluate the three dimension power Doppler indices together with uterine artery Doppler indices during the day of embryo transfer in predicting the outcome of ICSI cycle. Study design: One hundred and three healthy women with singleton pregnancy werprospective cohort study. Patient and methods: One hundred twenty patients were included in the study during ICSI cycles. This work was done at IVF unite of Dar El Teb hospital, Egypt. All patients included in the work had these criteria; age; 22–35 years, BMI; < 35 kg/m2, oligo- or oligoas- thenospermia. All patients received along agonist protocol of ovarian hyperstimulation and after follicular retrieval; embryos were trans- ferred at the stage of blastocyst. Three D Power Doppler was done at the day of embryo transfer. Quantitative pregnancy tests were done for every patient. The rates of clinical and ongoing pregnancy were estimated. All women were categorized into two categories: with pregnancy and without pregnancy. Results: Thirty-five percent of patients became pregnant. Our study showed non-significant differences in both groups regarding demo- graphic, clinical and laboratory data except for some vascular pa- rameters (endometrial VI, FI, VFI-subendometrial FI- u PI). Our study revealed a significant increase of some vascular parameters (endometrial VI, FI, VFI-subendometrial FI- u PI).and correlated to pregnancy. The endometrial VFI is the most sensitive vascular pa- rameter correlated to pregnancy. Conclusion: 3DPD is a useful non invasive predictor for IVF out- come.

Association between Body Mass Index and Reproductive Outcome in Women with Polycystic Ovary Syndrome Receiving IVF/ICSI-ET.

Objective To examine the association between body mass index (BMI) and the outcome of in vitro fertilization or intracytoplasmic sperm injection embryo transfer- (IVF/ICSI-ET) assisted reproduction in women with polycystic ovary syndrome (PCOS) receiving the ultra-long agonist protocol. Methods We retrospectively identified all women receiving IVF/ICSI-ET for the first time using the ultra-long protocol between January 2013 and January 2018 at our hospital. Only women at ≤35 years of age receiving the first cycle were analyzed. Results A total of 1782 women were included in the analysis: 42 were underweight, 742 were overweight, 198 were obese, and 800 were normal weight. Gonadotropin dosage and duration were comparable between underweight and normal weight groups but were significantly higher/longer in overweight and obese groups (P < 0.008). The number of oocytes retrieved was significantly lower in overweight and obese groups than in the normal weight group (P < 0.008). The number of transferable embryos was significantly higher in normal weight group than overweight and obese groups (P < 0.008). Embryo implantation rate, clinical pregnancy rate, full-term birth rate, and live birth rate did not differ among the 4 groups. The cycle cancellation rate was lower in the overweight and obese group than normal weight group (P < 0.008). The miscarriage rate was higher in the obese group than the normal weight group (P < 0.008). In multivariate logistic regression analysis, abnormal BMI was an independent risk for miscarriage (OR: 1.069, 95% CI 1.020, 1.122; P = 0.006). Conclusion Overweight and obesity are associated with poor outcomes in PCOS patients receiving ultra-long protocol. Measures to reduce body weight should be encouraged in overweight and obese PCOS women at ≤35 years of age prior to assisted reproductive technology (ART).

Serum Progesterone Level in Agonist and Antagonist Protocols on the Day of Human Chorionic Gonadotropin Triggering in Prediction of Intracytoplasmic Sperm Injection Outcome

Background:The potential association of serum progesterone on the day of human chorionic gonadotropin administration with the outcome of intracytoplasmic sperm injection [ICSI] cycles has been one of the major controversies in the endocrinology of ovarian stimulation. Aim of the work: This study was conducted to estimate the net effect of progesterone elevation on the day of human chorionic gonadotrophin [hCG] on pregnancy outcome in women undergoing fresh embryo transfer in control ovarian stimulation using long agonist and antagonist protocols. Patients and Methods:This is a prospective study included a total of 177 patients who were indicated for ICSI. The included cases were divided into three groups according to progesterone level at the day of hCG. Both progesterone and E2 were estimated at the day of triggering. Results:Serum progesterone levels did not differ between cases who got pregnancy and who did not (p=0.435). Estrogen/Progesterone ratio was not significantly different between pregnant and non-pregnant females (p= 0.842). Conclusion: Progesterone level on the day of hCG administration does not have any effect on ICSI outcome.

The effect of adenomyosis on IVF after long or ultra-long GnRH agonist treatment

Research questionDoes adenomyosis affect IVF independent of decreased ovarian reserve, and what are the characteristics and IVF outcome of the ultra-long gonadotrophin-releasing hormone (GnRH) agonist protocol in adenomyosis? DesignObservational cohort study of three groups of patients undergoing first cycle of IVF treatment with normal ovarian reserve: (A) 362 patients with adenomyosis using the ultra-long GnRH agonist protocol; (B) 127 patients with adenomyosis using the long GnRH agonist protocol; (C) 3471 patients with tubal infertility using the long GnRH agonist protocol. ResultsCompared with groups B and C, the number of oocytes retrieved in group A decreased, and the gonadotrophin dosage and duration in group A were higher (P < 0.001). In long GnRH agonist treatment, clinical pregnancy rate (OR 0.492, 95% CI 0.327 to 0.742, P < 0.001), implantation rate (OR 0.527, 95% CI 0.350 to 0.794, P = 0.002) and live birth rate (OR 0.442, 95% CI 0.291 to 0.673, P < 0.001) decreased and miscarriage rate (OR 3.078, 95% CI 1.593 to 5.948, P < 0.001) increased in adenomyosis patients compared with tubal infertility. For adenomyosis patients, clinical pregnancy rate (OR 1.925, 95% CI 1.137 to 3.250, P = 0.015), implantation rate (OR 1.694, 95% CI 1.006 to 2.854, P = 0.047) and live birth rate (OR 1.704, 95% CI 1.012 to 2.859, P = 0.044) increased in the ultra-long GnRH agonist treatment compared with long GnRH agonist treatments. ConclusionAdenomyosis could negatively affect IVF outcomes independent of ovarian reserve after long GnRH agonist protocol. Patients with adenomyosis following the ultra-long GnRH agonist protocol could have a better pregnancy outcome than those following the long GnRH agonist protocol.

Corifollitropin alfa for poor responders patients, a prospective randomized study

BackgroundPoor ovarian response remains one of the biggest challenges for reproductive endocrinologists. The introduction of corifollitropin alpha (CFA) offered an alternative option to other gonadotropins for its longer half-life, its more rapid achievement of the threshold and higher FSH levels. We compared two different protocols with CFA, a long agonist and a short antagonist, and a no-CFA protocol.MethodsPatients enrolled fulfilled at least two of the followings: AFC < 5, AMH < 1,1 ng/ml, less than three oocytes in a previous cycle, age > 40 years. Ovarian stimulation with an antagonist protocol was performed either with 300 UI rFSH and 150 UI rLH or 300UI HMG. In the long agonist group, after pituitary suppression with triptorelin, CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. In the short antagonist group CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. The primary objective was the effect on the number of oocytes and MII oocytes. Secondary objective were pregnancy rates, ongoing pregnancies and ongoing pregnancies per intention to treat.ResultsThe use of CFA resulted in a shorter lenght of stimulation and a lower number of suspended treatments. Both the CFA protocols were significantly different from the no-CFA group in the number of retrieved oocytes (p < 0,05), with a non-significant difference in favour of the long agonist protocol. Both CFA groups yielded higher pregnancy rates, especially the long protocol, due to the higher number of oocytes retrieved (p < 0,05), as implantation rates did not differ. The cumulative pregnancy rate was also different, due to the higher number of cryopreserved blastocysts (p < 0,02).ConclusionsThe long agonist protocol with the addition of rFSH and rLH showed the best results in all the parameters. A short antagonist protocol with CFA was less effective, but not significantly, although provided better results compared to the no-CFA group. We suggest that a long agonist protocol with CFA and recombinant gonadotropins might be a valuable option for poor responders.Trial registrationThe study was approved by the local Ethics Committee (EudraCT2015–002817-31).

The ovulation trigger\u2013OPU time interval of different ovarian protocols in ART: a retrospective study

PurposeTo explore the trends of oocyte and pregnancy outcomes over the ovulation trigger–OPU (oocyte pickup) time interval in four mainly used COH protocols.MethodsThis retrospective study was conducted between January 2013 and July 2018. The IVF/ICSI cycles of the patients with normal ovarian reserve were included. The number of total patients was 4673, which consisted of long agonist protocol (n = 819), short agonist protocol (n = 1703), mild stimulation protocol (n = 1627), and GnRH antagonist protocol (n = 524). The primary outcome was mature oocyte rate.ResultsThe ovulation trigger–OPU time interval and COH protocol were related to cycles with > 80% MII oocytes. Four protocols showed apparently different trends of retrieved oocyte rate and mature oocyte rate over the ovulation trigger–OPU time interval, and the long agonist protocol had the most delayed time interval than other three COH protocols in retrieving more than 60% oocytes (35.4–39.6 h vs. 34.6–38.6 h vs. 32.5–37.5 h vs. 33.8–37.7 h) and getting more than 80% mature oocytes (35.0–39.7 h vs. 36.0–37.7 h vs. 34.1–35.5 h vs. 34.5–36.3 h). And the adjusted odds ratio (OR) of the cumulative live birth rate (CLBR) (OR 1.360, 95% Confidence Interval (CI) 1.156–1.549, P < 0.05) significantly increased with the trigger–OPU time interval in the long agonist protocol.ConclusionsFor getting more and mature oocytes, the ovulation trigger–OPU time intervals should be gradually prolonged from the mild stimulation protocol, the GnRH antagonist protocol, and the short protocol to the long agonist protocol. And the prolonged ovulation trigger–OPU time interval in the long agonist protocol brings higher live birth rate (LBR) and CLBR.