Agonist Protocol Research Articles

A live birth with unexpectedly low serum human chorionic gonadotropin level on day 11 after blastocyst embryo transfer: a case report

ObjectiveTo report a very rare case of live birth with unexpectedly low serum hCG level on day 11 after blastocyst embryo transfer.DesignCase report.SettingPrivate infertility center.Patient(s)A 30-year-old nulliparous woman presented with PCOS and 1 year of infertility.Interventions(s)Conventional IVF was scheduled and a long-acting agonist protocol was selected.Main Outcome Measure(s)Maternal serum hCG levels and transvaginal ultrasound exams for the embryo’s well-being.Result(s)The hCG level was 11.6 IU/L on day 11 after the transfer of two blastocyst embryos, which was considered as either failing or extrauterine pregnancy. After blood titration, there were delayed hCG increases. A series of transvaginal ultrasounds also indicated a delayed but normal-appearing intrauterine pregnancy. A healthy baby boy was delivered at term by means of cesarean section.Conclusion(s)A low initial serum hCG level may be associated with certain maternal or fetal characteristics and IVF treatment variables. Close conservative observation is warranted before undertaking any therapeutic intervention.

Impact of Gonadotropin-Releasing Hormone Agonist Pre-treatment on the Cumulative Live Birth Rate in Infertile Women With Adenomyosis Treated With IVF/ICSI: A Retrospective Cohort Study.

Introduction: Although pre-treatment with a GnRH agonist can reduce the size of adenomyosis lesions, the supra-physiological hormone level induced by controlled ovarian hyperstimulation (COH) may negate the usefulness of the GnRH agonist in patients with adenomyosis lesions, leading to continued poor outcomes in fresh embryo transfer cycles during in vitro fertilization (IVF). It is unclear whether GnRH agonist pre-treatment before starting the long GnRH agonist protocol for IVF/ICSI (intracytoplasmic sperm injection) can improve cumulative live birth rate (CLBR) of infertile women with adenomyosis.Method: In this retrospective cohort study, a total of 374 patients diagnosed as adenomyosis (477 cycles) underwent IVF/ICSI with long GnRH agonist protocol with or without GnRH agonist pre-treatment between January 2009 and June 2018. Logistic regression was used to assess the association between GnRH agonist pre-treatment and pregnancy outcome after adjusting for confounding factors.Results: The live birth rate in fresh embryo transfer cycles was higher in the non-pre-treatment group than in the GnRH agonist pre-treatment group (37.7 vs. 21.2%, P = 0.028); the adjusted odds ratio (OR) for the long agonist protocol without pre-treatment was 1.966 (95% CI: 0.9–4.296, P = 0.09). The CLBR was higher in the non-pre-treatment group than in the GnRH agonist pre-treatment group (40.50 vs. 27.90%, P = 0.019); the adjusted OR for the long agonist protocol without pre-treatment was 1.361 (95% CI: 0.802–2.309, P = 0.254).Conclusion: Our results indicated that GnRH agonist pre-treatment before starting the long GnRH agonist protocol does not improve the live birth rate in fresh embryo transfer cycles or CLBR in infertile women with adenomyosis after IVF/ICSI treatment when compared to that in non-pre-treated patients. A subsequent prospective randomized controlled study is needed to confirm these results.

Maternal Serum Levels of Interferon-gamma, Tumor Necrotic Factor-alpha and Progesterone of Infertile Women on In vitro Fertilization before and after Treatment

Background: In vitro fertilization (IVF) is an assisted reproductive technology (ART) that is widely used globally in the treatment of infertility. Infertility can occur due to male factors, female factors or both.
 Aim: This is the first Nigerian study that sets out to observe the levels and relationship between circulating pro-inflammatory cytokines (IFN-γ, TNF-α) and progesterone (PG) in Nigerian women undergoing in vitro fertilization pre and post treatment and their possible effect on pregnancy outcome.
 Materials and Methods: This observational study randomly selected sixty-two (62) infertile females below 45 year of age who enrolled in the IVF treatment at Lily Hospitals, Warri and Shepherd Specialist Hospital, Warri, Southern Nigeria. Only data of the thirteen (13) infertile females who became pregnant after the IVF treatment where followed up and presented in this study. Five (5) ml of whole blood were collected into plain tubes on day 3 of the menstrual cycle of all the participants from the ante-cubital vein before and after IVF procedure using standard laboratory collection technique. Ovarian stimulation was done using the long gonadotropin-releasing hormone agonist protocol. Oocyte retrieval transfer was done using ultrasound-guided fine-needle aspiration and embryo transfer was done using ultrasound-guided embryo transfer. IFN-γ, TNF-α and PG were estimated using enzyme-linked immunosorbent assay method.
 Results and Conclusion: Significant increase in the levels of TNF-α and PG at the second trimester and third trimester of pregnancy when compared with the first trimester of pregnancy (p = 0.000). While the level of IFN-γ was significantly increased in the second trimester of pregnancy when compared with the first trimester of pregnancy (p = 0.000). It is evident from the study that both pro-inflammatory cytokines (IFN-γ and TNF-α) act in synergy to maintain the level of progesterone which act as an anti-inflammatory agent to regulate the activities of the pro-inflammatory cytokines for successful oocytes implantation and maturation.

The effect of different estradiol levels on carotid artery distensibility during a long agonist IVF protocol

BackgroundThis study was made to figure out, does low and high estradiol levels during in vitro fertilization (IVF) cycles have a different effect on carotid artery distensibility (Cdis), carotid artery diameter (Cdia), blood pressure and metabolic factors? Can the stimulation protocol be considered safe to women’s vasculature?MethodsWe studied 28 women having a long agonist protocol IVF-treatment in Kuopio University Hospital during the years 2011–2016. Patients were examined at three time points: in the beginning of their own period (low estradiol), during the gonadotrophin releasing hormone (GnRH) analogue downregulation (low estradiol) and during the follicle stimulating hormone (FSH) stimulation (high estradiol). Women served as their own controls and their menstrual phase (2- to 5-day period after the beginning of menstruation with low estrogen) was used as the reference. Cdis and Cdia were assessed using ultrasound. Blood pressure, weight, estradiol levels and lipids were monitored.ResultsCdis, Cdia, systolic and diastolic blood pressures peaked during the GnRH-analogue treatment with the lowest estradiol levels. Cdis, Cdia and systolic blood pressures declined by 11% (P = 0.002), 3,8% (P < 0.001) and 2,5% (P = 0.026) during the FSH-stimulation when the estradiol levels were high. Cdis correlated significantly (P < 0.05) with systolic blood pressure, diastolic blood pressure and triglycerides in high estrogenic environment and with diastolic blood pressure (P < 0.05) when estrogen profiles were low.ConclusionsCarotid artery stiffens during the high estradiol levels compared to low levels and this was not explained by the higher diameter of the carotid artery, hyperlipidemia or blood pressure profiles. All the changes in Cdis and Cdia are variations of normal, and if there is no history of cardiovascular problems, it can be considered, that the stimulation protocol is not hazardous to vasculature.

Does an FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? A randomized, double-blinded, placebo-controlled study.

Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI. Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS). This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation. Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000-10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS. There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI -6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively. This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger. Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient. This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246). 20 May 2012. 10 June 2012.

GnRH antagonist alters the migration of endometrial epithelial cells by reducing CKB.

Some studies have demonstrated that the implantation rate of fresh transfer cycles is lower in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol than in the GnRH agonist (GnRH-a) protocol during in vitro fertilization (IVF). This effect may be related to endometrial receptivity. However, the mechanisms are unclear. Here, endometrial tissues obtained from the mid-secretory phase of patients treated with GnRH-a or GnRH-ant protocols and from patients on their natural cycle were assessed. Endometrial expression of B-type creatine kinase (CKB), which plays important roles in the implantation phase, was significantly reduced in the GnRH-ant group. At the same time, expression of the endometrial receptivity marker HOXA10 was considerably reduced in the GnRH-ant group. GnRH-ant exposure in endometrial epithelial cells (EECs) in vitro decreased CKB expression and ATP generation and blocked polymerization of actin. Furthermore, in vitro GnRH-ant-exposed Ishikawa cells showed enhanced F-actin depolymerization, and these effects were rescued by CKB overexpression. Similar effects were observed after CKB knockdown, and these effects were rescued by CKB overexpression. Moreover, cell migration was decreased in CKB-knockdown Ishikawa cells compared with that in control cells, and this effect was also rescued by CKB overexpression. Overall, these findings showed that GnRH-ant affected CKB expression in EECs, resulting in cytoskeletal damage and migration failure. These results provide insight into the roles and molecular mechanisms of GnRH-ant treatment in the endometrium.

Additional luteal support might improve IVF outcomes in patients with low progesterone level in middle luteal phase following a GnRH agonist protocol

Aim The purpose of the study was to explore the efficacy of additional luteal support (ALS) for patients with low progesterone (P4) level in the middle luteal phase. Methods A retrospective study of 1401 women who underwent their first in vitro fertilization (IVF) treatment with a GnRH agonist protocol was analyzed. Patients were divided into five groups according to P4 level in the middle luteal phase (group I>40ng/mL, group II 31–40 ng/mL, group III 21–30 ng/mL, group IV 11–20 ng/mL and group V 0–10 ng/mL. Besides routine luteal support, the group V was offered with additional oral dydrogesterone 10 mg twice daily to HCG test (ALS group). Results After a multiple regression analysis, a similar higher hCG positive rate, clinic pregnancy rate and lower early pregnancy loss rate were achieved in group I and group V. In contrast to group I, group IV demonstrated significant lower HCG positive rate (OR = 0.65 [0.43; 0.99], p = .05), lower clinic pregnancy rate (OR = 0.60 [0.41; 0.88], p < .01) and significant higher early pregnancy loss rate (OR = 1.80 [1.08; 2.99], p = .02). The group III also resulted in significant lower clinic pregnancy rate (OR = 0.56 [0.36; 0.87], p = .01). The live birth rate tended to be higher in group I and group V but without a significant difference. Conclusion Following agonist protocol, additional luteal support might improve IVF outcomes in patients with low serum P4 level in the middle luteal phase.

GnRH agonis short protocol versus GnRH antagonist flexible protocols in poor responder undergoing in vitro fertilization treatment.

Objective: To compare the short agonist and flexible antagonist protocols in the management of poor responders to standerd long down regulation protocol. Design: Randomized prospective comparative study. Setting: private IVF center(Engab). Patient(s): One hundred poor-responder (IVF)(ICSI), who responded poorly to the standerd long down- regulation protocol in their first treatment cycle. Intervention(s): Peak serum E2 was assayed on the day of hCG administration. Main Outcome Measure(s): primary outcome: number of HMG ampoules used, peak E2 at the triggering day, number of oocytes retrieved, number of metaphase II oocytes, fertilization rate, embryo quality and number of embryos transferred.cycle cancellation. secondary outcome: pregnancy rate , miscarriage rate . Result(s): GnRH-antagonist protocol shows increased – non significant- pregnancy rate and decreased - non significant - miscarriage rate than agonist short protocol, however agonist short protocol appears to be more effective than the GnRH-antagonist protocol in terms of number of FSH ampules, peak E2 level, fertilization rate, and top-quality embryos transferred in poor-responder. Conclusion(s): The probability of pregnancy might be better with the use of the antagonist protocol, also flexible antagonist protocol is a simpler and more patient friendly method of ovarian stimulation compared with the short agonist protocol.

Gonadotrophin-releasing hormone agonist triggering may improve central oocyte granularity and embryo quality.

This study aimed to describe outcomes in four women aged 28-34 years with central cytoplasmic granulation (CCG) of the oocytes who underwent in vitro fertilization/intracytoplasmic sperm injection (ICSI) using gonadotrophin-releasing hormone (GnRH) agonist to replace human chorionic gonadotrophin (hCG) as a trigger of final oocyte maturation. The initial ICSI procedure showed that all four women had CCG of the ooplasm and poor quality embryos. Subsequent ICSI used an antagonist protocol with a GnRH agonist trigger replacing the agonist protocol, plus hCG triggered ovulation. Ooplasm and embryo quality were improved in all four patients. All four became pregnant and gave birth to live infants. This study provides GnRH agonist triggering that may improve ooplasm granularity and embryo quality.

Factors associated with extremely high progesterone concentrations on the day of HCG administration

ObjectiveProgesterone elevation on the day of human chorionic gonadotropin (hCG) administration remains one of the most controversial topics in reproductive endocrinology. Factors associated with these increases have not been fully determined. The purpose of our study is to investigate factors associated with extreme progesterone elevation on the day of human chorionic gonadotropin (hCG) administration. Materials and methodsThis retrospective observational, single-center cohort study recruited 2000 fresh in vitro fertilization (IVF) and/or intracytoplasmic sperm injection(ICSI)-embryo transfer cycles from January 2000 to December 2014 in our institution. ResultsWhen cycles were divided into those with progesterone <1.94 ng/mL (n = 1791) and ≧1.94 ng/mL (n = 209) on the day of hCG administration, five factors were positively associated with highly elevated progesterone concentration: protocol (GnRH agonist versus antagonist; odds ratio [OR = 2.786]), number of dominant follicles (OR = 1.098), total dose of follicle stimulating hormone (FSH) used (OR = 1.023), elevated luteinizing hormone (LH) (OR = 1.085) and estradiol (E2; OR = 1.001) concentrations on the day of hCG administration (p < 0.001 each). After omitting the protocol effect, the remaining factors showed limited contributions to highly elevated progesterone (ORs = 0.95–1.2). ConclusionsThe factor showing the greatest association with extreme progesterone elevation was use of the GnRH agonist protocol.

Acute cardiovascular changes in women undergoing in vitro fertilisation (IVF), a systematic review and meta-analysis

ObjectivesOvarian stimulation during fertility treatment leads to profound maternal physiological changes. Women undergoing in vitro fertilisation (IVF) may be at an increased risk of future cardiovascular morbidity, though little is known about the effects on maternal cardiovascular function. We aim to systematically review whether IVF treatment is associated with changes in maternal haemodynamic parameters, and the effects of different protocols. Study DesignA systematic review and meta-analysis of English language studies identified on Medline and EMBASE database, between 1978, to 2019. Search terms: IVF, maternal haemodynamics, and cardiovascular. Studies reporting on ovulation induction, intrauterine insemination, and oocyte donation were excluded. Methodological quality was assessed by using the adapted Critical Appraisal Skills Programme (CASP) checklist. A meta-analysis was conducted for blood pressure and heart rate on patients undergoing the long GnRH agonist protocol according to Cochrane guidelines. We considered four time points in the IVF cycle, in chronological order: pre-treatment, pituitary down regulation, peak oestradiol and the luteal phase. ResultsNine suitable studies were identified; four fulfilled the criteria for meta-analysis. Two studies measuring heart rate found a significant increase in heart rate from pituitary down-regulation to peak estradiol levels, which was supported by the meta-analysis (3.78 ± 2.18 (p= < 0.0001)). Three studies reported a significant decrease in blood pressure from baseline, with those suitable for meta-analysis showing a significant decrease in mean arterial pressure (-2.08 ± 1.79 (p= < 0.0001)). Cardiac functional changes were reported for all studies and the changes depended on the type of protocol used. ConclusionsIn Vitro Fertilisation leads to acute changes in maternal haemodynamics at different time points of the stimulation protocol. We found an increase in heart rate from pituitary down-regulation to peak estradiol levels and a significant decrease in blood pressure from baseline or pituitary down-regulation to the luteal phase. Cardiac functional changes were reported for all studies on the agonist protocol, but no significant changes were found using the antagonist protocol. It remains unclear as to whether these acute changes were associated with pregnancy complications or chronic cardiovascular sequelae.

Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis.

This systematic review and meta-analysis of comparative studies investigated whether progestins are as effective as gonadotrophin releasing hormone (GnRH) analogues for pituitary suppression in assisted reproduction. The primary outcome was live birth rate per woman. Secondary outcomes were live birth or ongoing pregnancy per woman and per embryo transfer, ongoing pregnancy, clinical pregnancy, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotrophin consumption. Adverse events included miscarriage, ectopic pregnancy and multiple pregnancy rates. The GRADE system was used to assess the quality of evidence. Seven studies involving a total of 2047 women were included. Three studies compared a progestin with a GnRH antagonist and four studies compared a progestin with a GnRH agonist. Most studies are non-randomized and report outcomes per embryo transfer, rather than per woman. Although progestins were similar to GnRH antagonists in effectiveness and safety parameters, they were associated with significantly higher live birth or ongoing pregnancy per embryo transfer compared with the short GnRH agonist protocol (RR 1.49, 95% CI 1.16 to 1.91). Progestin primed stimulation lasted significantly longer (mean difference 0.61 days, 95% CI 0.33 to 0.89) and required significantly more gonadotrophins (mean difference 433.2 IU, 95% CI 311.11 to 555.19) than the short GnRH agonist protocol, but the differences were clinically negligible. Safety parameters were similar between progestins and GnRH agonists. In conclusion, progestins can effectively prevent premature ovulation in assisted reproductive technology cycles. If larger and well-designed studies confirm these findings, progestins may be an effective and low-cost alternative to GnRH analogues when a fresh embryo transfer is not planned owing to a medical indication.

ESHRE guideline: ovarian stimulation for IVF/ICSI†.

ESHRE guideline: ovarian stimulation for IVF/ICSI†.

The ratio of exogenous Luteinizing hormone to Follicle stimulating hormone administered for controlled ovarian stimulation is associated with oocytes' number and competence.

We performed a retrospective study aiming to study the relationship between the ratio of the exogenous luteinizing hormone to follicle stimulating hormone (LH/FSH) administrated for controlled ovarian stimulation (COS) and the number and competence of the oocytes retrieved for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Eight hundred sixty-eight consecutive infertile patients (mean age 34.54 ± 4.01 years, mean anti-Müllerian hormone (AMH) 2.94 ± 2.07 ng/ml) treated with long agonist protocol and a mixed gonadotropin protocol (human menopausal gonadotropin in association with recombinant FSH (recFSH)) who performed IVF/ICSI between January 2013 and February 2016, were included. Patients with severe male factor were excluded. LH/FSH was calculated based on total doses of the two gonadotropins. We found, after adjustment for confounders, a positive relationship between LH/FSH and the retrieved oocytes’ (β = 0.229, P<0.0001) and zygotes’ number (β = 0.144, P<0.0001) in the entire study group and in subgroups according to age (<35 and ≥35 years) and ovarian reserve (AMH < 1.1 and ≥ 1.1 ng/ml). The fertilization rate was positively associated with LH/FSH in patients with LH/FSH in the lowest three quartiles (below 0.77) (β = 0.096, P=0.034). However, patients in the fourth quartile of LH/FSH had a lower fertilization rate as compared with patients in quartiles 1–3 which, after adjustment for covariates, was only marginally negatively related with LH/FSH (β = −0.108, P=0.05). In conclusion, our results suggest that the adequate LH/FSH administrated during COS can improve the oocytes’ and zygotes’ number in IVF/ICSI cycles, but also the fertilization rate when a certain proportion of LH/FSH is not exceeded.

The Association Between Elevated Progesterone Level on Day of hCG Trigger and Live Birth Rates in ART Cycles: A Single Centre Observational Study.

Background:The advent of ovarian stimulation within an in vitro fertilization (IVF) cycle has resulted in modifying the physiology of stimulated cycles and has helped optimize pregnancy outcomes. In this regard, the importance of progesterone (P4) elevation at time of human chorionic gonadotrophin (hCG) administration within an IVF cycle has been studied over several decades. Our study aimed to evaluate the association of P4 levels at time of hCG trigger with live birth rate (LBR), clinical pregnancy rate (CPR) and miscarriage rate (MR) in fresh IVF or IVF-ICSI cycles.Methods:This was a retrospective cohort study (n=170) involving patients attending the Centre for Reproductive and Genetic Health (CRGH) in London. The study cohort consisted of women undergoing controlled ovarian stimulation using GnRH antagonist or GnRH agonist protocols. Univariate and multiple logistic regression analyses were used to evaluate the association of clinical outcomes. Differences were considered statistically significant if p≤0.05.Results:As serum progesterone increased, a decrease in LBR was observed. Following multivariate logistical analyses, LBR significantly decreased with P4 thresholds of 4.0 ng/ml (OR 0.42, 95% CI:0.17–1.0) and 4.5 ng/ml (OR 0.35, 95% CI:0.12–0.96).Conclusion:P4 levels are important in specific groups and the findings were statistically significant with a P4 threshold value between 4.0–4.5 ng/ml. Therefore, it seems logical to selectively measure serum P4 levels for patients who have ovarian dysfunction or an ovulatory cycles and accordingly prepare the individualized management packages for such patients.

Role of gene polymorphisms related to progesterone elevation in women undergoing long GnRH agonist protocols.

Can single-nucleotide polymorphisms (SNP) of genes related to progesterone synthesis predict the risk of premature serum progesterone elevation in women undergoing gonadotrophin-releasing hormone agonist protocols for ovarian stimulation? A total of 765 women were divided into high progesterone and normal progesterone groups according to progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration, with the 75th percentile as the threshold between the group. Associations were analysed of genetic information from whole exome sequencing and the clinical characteristics of the two groups to identify the relationship between SNP, haplotypes and serum progesterone elevation. Among 40 common SNP of eight genes (FSHR, LHCGR, ESR1, ESR2, PGR, HSD3B1, CYP11A1 and CYP17A1), no statistical significance between the high and normal progesterone groups was identified in the distribution of genotypes and allele frequencies after multiple test correction to adjust the false discovery rate (PFDR > 0.05). When compared with the most common haplotypes of each gene, haplotype GAAG in CYP17A1 was associated with a 1.44-fold increased risk of progesterone elevation (95% confidence interval [CI] 1.22-1.69, PFDR < 0.001), while haplotypes of the following genes showed a decreased risk of progesterone elevation: haplotype CC in FSHR and LHCGR (0.66-fold, PFDR = 0.020, and 0.64-fold, PFDR < 0.001, respectively), CA in ESR1 (0.90-fold, PFDR < 0.001), TCTGG in ESR2 (0.92-fold, PFDR = 0.007) and GAACC in HSD3B1 (0.42-fold, PFDR < 0.001). Polymorphism in genes involved in enzymes or hormone receptors in the progesterone synthesis pathway may have a role in modifying risk of serum progesterone elevation.

Assessment of Oxidative Stress Changes in Serum and Follicular Fluid in Relevance to GnRH rival Protocol in Iraqi Infertile Ladies Undergoing ICSI

Background: Literary works about the role of rival convention in relationship with oxidative pressure are opposing and there is no reasonable agreement in distributed ripeness articles about the role of opponent reproduction convention with this respect. In reality, a few creators support the presence of expanded oxidative initiated oocyte harm in ladies experiencing ART's; regardless, others have denied such a perception. Hence, the present investigation was arranged so as to think about the conceivable oxidative or hostile to oxidative potential controlled by foe convention.&#x0D; Aim of the study: The aim of the current study was to evaluate the serum and follicular ROS concentration in women undergoing ICSI contrasted between two groups, one receiving conventional antagonist protocol and the other receiving conventional agonist protocol.&#x0D; Patients and Methods: The current case control study included two groups of subfertile women. The study group included 57 women receiving antagonist protocol, whereas, the control group included 10 subfertile women receiving agonist protocol. The study was carried out at High Institute of Infertility Diagnosis and Assisted Reproductive Technologies at Al- Nahrain University. The study started on April 2018 and extended to March 2019. Women in both groups were subjected to ICSI procedure according to procedures and techniques adopted in High Institute of Infertility Diagnosis and Assisted Reproductive Technologies at Al- Nahrain University with a single basic difference concerning the ovarian stimulation protocol.&#x0D; Results: Overall clinical pregnancy rate was 44.7 % being significantly higher in antagonist group in comparison with agonist group 50.9 % versus 10.01 %, respectively (P = 0.019). There was no significant difference in the concentration of ROS at cycle day 2 between antagonist and agonistgroups (P = 0.561). There was highly significant difference in the serum concentration of ROS at day of ova pickup between antagonist and agonist groups (P = 0.009); being less in antagonistgroup and there was highly significant difference in the follicular fluid concentration of ROS between antagonist and agonist groups (P = 0.003); being less in antagonist group.&#x0D; Conclusions: Antagonist protocol is associated with significantly higher positive pregnancy outcome in comparison with agonist protocol because of the anti-oxidant effect attributed to antagonist use.

Ovulation induction with high progesterone levels may be more suitable for elderly patients with low ovarian response

BackgroundThe objective of this study was to explore the outcomes of using the progestin-primed ovarian stimulation (PPOS) protocol in aged infertile women. The patients recruited in the study had displayed a poor ovarian response (POR) in the first IVF/ICSI-ET cycles with the ultra-short gonadotropin-releasing hormone agonist (GnRH-a) protocols. Materials and methodsA self-controlled retrospective study was conducted to investigate the clinical outcomes of 117 aged infertile women who met the inclusion criteria. The patients were grouped into two; group B included patients who had displayed a poor ovarian response (POR) in the first IVF/ICSI-ET cycle with the ultra-short GnRH-a protocol. Group A was made up of patients who underwent the PPOS protocol in the second cycle. The study was done between January 2015 to May 2018 in the reproductive and genetic centre of integrated traditional and western medicine, Affiliated hospital of Shandong University of traditional Chinese medicine. Reproduction-related clinical outcomes in the two groups were compared. ResultsThere were no statistically significant differences in the serum levels of LH, E2, and P on the trigger day between group A and group B (P＞0.05). The number of follicles with a diameter > 14 mm was significantly higher in the PPOS protocol patients than in the ultra-short GnRH-a protocol group (4.83 ± 2.82 vs. 3.25 ± 2.53, P < 0.01). The duration and total dosage of gonadotropin of the PPOS protocol group were less than in the previous ultra-short GnRH-a protocol, although the statistical differences were not significant (P > 0.05). The number of eggs obtained in the PPOS group was significantly higher than that of the previous one (4.29 ± 3.11 vs. 2.76 ± 2.33, P < 0.05). The numbers of MII eggs, cleavage, 2 P N, transplantable embryos, and high quality embryos were higher in the PPOS protocol group than that in the ultra-short protocol group. However, the differences between the two groups in all the above parameters were not statistically significant (P > 0.05). The rate of high-quality embryos was significantly higher in the PPOS protocol group than in the ultra-short protocol group (38.61(100/259) vs. 32.02(65/203), P < 0.05). Although not statistically significant (P > 0.05), the abortion rate of the PPOS protocol group was higher than that of the ultra-short protocol group. The clinical pregnancy and live birth rates were significantly higher in the PPOS protocol group than in the ultra-short protocol group (p < 0.05). The clinical pregnancy rates in the PPOS protocol group and the ultra-short protocol group were 32.35 % and 25.53 % respectively while the live birth rates were 27.45 % and 21.28 % respectively. ConclusionCompared with the ultra-short protocol, the PPOS protocol improves the number of follicles, the number of eggs, clinical pregnancy, and live birth rates in POR patients. The PPOS protocol could, therefore, provide a novel treatment strategy for inducing ovulation in POR patients.

Agonist Versus Antagonist in Intracytoplasmic Sperm Injection Cycles: Which Is the Best?

Objectives: The comparison of gonadotropin-releasing hormone (GnRH) agonist against GnRH antagonists regarding the pregnancy rate and effect of various predictors on pregnancy outcomes. Materials and Methods: This prospective comparative study involved 189 women who underwent intracytoplasmic sperm injection (ICSI) cycles and were divided into agonist (107 patients) and antagonist arm (82 patients) groups. The chemical and clinical pregnancy rate was the main outcome and the other outcomes included the number and quality of oocyte measurement and pregnancy outcomes. Results: Based on the results, the agonist protocol showed a higher rate of pregnancy (32.7%, 95% CI: 23.9-42.4%) compared to the antagonist protocol (22.0%, 95% confidence interval (CI): 13.6-32.5%) with the odds ratio (OR) of (95% CI) = 1.73 (0.89-3.35). The results further revealed that the count of retrieved oocytes, count of M2 oocytes, count of fertilized oocytes, count of embryos, and the fertilization percent out of total retrieved oocytes were higher in the agonist arm compared to the antagonist arm. In the multivariate analysis after adjusting for the confounders, the agonist protocol had higher odds of a successful pregnancy compared to the antagonist protocol by 57% (partial OR = 1.57, P value = 0.23). Conclusions: In general, the agonist protocol offers a favourable outcome in comparison to the antagonist arm, and there seems to be an intrinsic benefit for the agonist protocol, which is not explained by the higher number of transferred embryos.

Cumulative Live Birth Rates in Low Prognosis Patients According to the POSEIDON Criteria: An Analysis of 26,697 Cycles of in vitro Fertilization/Intracytoplasmic Sperm Injection.

Objective: The POSEIDON criteria are used to stratify patients with low prognosis after assisted reproductive technology (ART) treatment. Since its introduction, there has been no large study about the prognosis of the POSEIDON population. We used the POSEIDON criteria in Chinese women who underwent repeated ART treatment and analyzed the association between POSEIDON criteria and the cumulative live-birth rate (CLBR).Methods: This was a retrospective cohort study of 62,749 women (97,388 cycles) who underwent ART treatment at the Reproductive and Genetic Hospital of CITIC-XIANGYA between January 2014 and June 2017. Among them, 19,781 (31.52%) women fulfilled the POSEIDON criteria, including 26,697 cycles. The optimal and conservative CLBRs within a complete IVF/ICSI treatment cycle were calculated, as well as the CLBRs following repeated ovarian stimulation cycles.Results: In POSEIDON groups 1, 2, 3, and 4, the optimal and conservative CLBRs of three complete consecutive in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were 83.87 and 66.06%, 53.67 and 37.72%, 44.24 and 27.98%, and 14.20 and 9.68%, respectively. The POSEIDON stratification [group 2: odds ratio (OR) = 2.319, 95% confidence interval (CI): 2.131–2.525, P < 0.001; group 3: OR = 1.356, 95% CI: 1.005–1.828, P = 0.046; group 4: OR = 3.525, 95% CI: 2.774–4.479, P < 0.001; all vs. group 1] and ovarian stimulation protocol [gonadotropin-releasing hormone (GnRH) antagonist protocol: OR = 1.856, 95% CI: 1.640–2.100, P < 0.001; other protocols: OR = 1.651, 95% CI: 1.155–2.361, P = 0.006; both vs. long GnRH agonist protocol] were associated with live birth in the first stimulation cycle. For the second stimulation cycle, the POSEIDON stratification (except POSEIDON group 3) and ovarian stimulation protocol were associated with live birth. A change in ovarian stimulation protocol was not associated with an improvement in the live birth rate.Conclusions: More than 30% of women who undergo IVF/ICSI treatment may be classified as low prognosis. Different reproductive outcomes were observed among the four POSEIDON groups. The most optimal outcomes after three successive cycles of IVF/ICSI treatment were observed in groups 1, 2, and 3.