GnRH Agonist Protocol Research Articles

The effect of coasting on the outcome of intracytoplasmic sperm injection: comparable analysis of GnRH agonist and antagonist cycles

Introduction: One of the preventive strategies in case of impeding ovarian hyperstimulation syndrome (OHSS) is coasting. The aim of this study was to compare the effect of coasting in high responder patients treated with gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocol for intracytoplasmic injection and embryo transfer. Materials and Methods: This retrospective study was conducted in the infertility unit in a private hospital. The study group included women who underwent an intra-cytoplasmic sperm injection (ICSI) cycle with a coasted period during ovulation induction from 2006 to 2013. The cycles outcome of cycles were compared between GnRH agonist (n=226) and GnRH antagonist (n=110) coasting cycles. Results: Women's age and other baseline characteristics of the groups were similar. Coasting was significantly more required in GnRH agonist cycles compared to GnRH antagonist cycles (11.8% vs. 4.5%, respectively, OR = 2.63, p p = 0.903). Moderate-severe OHSS occurred in 13 (5.7%) cases in the GnRH agonist group and three (2.7%) cases in the GnRH antagonist group (p = 0.343). In the GnRH agonist group, the longer duration of coasting (≥ four days) was associated with the lowest live birth rate (27.2%), but it did not reach a statistical significance. Conclusions: Live birth and moderate/severe OHSS rates are similar in the GnRH agonist and the GnRH antagonist cycles with coasting. Despite the lack of statistical significance, ≥ four days of coasting is related to the lowest live birth rate through ICSI compared to < four days of coasting in the GnRH agonist cycles.

Serum progesterone concentrations before and after human chorionic gonadotropin triggering and invitro fertilization : Intracytoplasmic sperm injection cycle outcome in long gonadotrophin releasing hormone agonist protocol

Objective: To assess the impact of serum progesterone concentrations before and after HCG triggering on IVF/ICSIcycle outcomes in long GnRHa protocol.Patients and Methods: This is a single-center prospective observational cohort study, in which 102 IVF/ICSI patients with normal cycle day 2 basal hormones were recruited and underwent ovarian stimulation using the long GnRHa protocol. Serum progesterone on the day of HCG trigger; one day after, progesterone/estradiol was assessed and correlated with pregnancy rates, the total dose of used gonadotropins, serum estradiol level on day of trigger, the number of collected oocytes, the number of metaphase II oocytes and the quality of transferred embryos.Results: 96 women were included in the analysis. In our study, the receiver-operating characteristic (ROC) analysis was used to gain more diagnostic accuracy. Our data according to ROC analysis showed that the P levels on the day of hCG trigger, and its levels one day after and P/E2 on the day of hCG trigger had no role in prediction of clinical pregnancy rates. There was significant correlation between the serum progesterone levels before and after HCG triggering with the total dose of gonadotropins used. They also correlated strongly with serum estradiol level on day of trigger, the number of collected oocytes and the number of metaphase II oocytes.Conclusion: Peri-ovulatory serum progesterone concentrations cannot predict pregnancy rates in IVF/ICSI cycles using long GnRHa protocol.

Case Report of Ectopic Pregnancy during Controlled Ovarian Stimulation without Oocytes Harvested and Late Ovarian Hyperstimulation Syndrome

Here we reported a rare case of misdiagnosed ectopic pregnancy (EP) due to unintended ovulation during controlled ovarian stimulation (COS) in GnRH agonist cycle, resulting in no oocytes harvested and late hyper-stimulation syndrome (OHSS). The patient was a 33-year old primary infertile woman due to male’s factors and underwent her second in vitro fertilization (IVF) cycle using GnRH agonist protocol, and no oocytes harvested on ovum picked-up (OPU) day. The start of gonadotropin usage was on day 8th of her period, and the P level increased rapidly and strangely high from day 8th after gonadotropin usage. The E2 level and follicles grew normally but finally no oocytes harvested. She was diagnosed as late ovarian hyper-stimulation syndrome (OHSS) 7 days after OPU. 20 days after OPU, no menstruation come and a positive urine test of hCG were reported. And the patient was diagnosed as EP by laparoscopy. In conclusion, rapidly increased P level, no oocyte retrieval and late onset of OHSS should be very important clues to diagnose this misdiagnosed EP.

Ultrasound and hematological changes during early luteal phase in women at high risk for developing ovarian hyperstimulation syndrome.

To assess ultrasound and hematological changes during the early luteal phase following triggering of final oocyte maturation with human chorionic gonadotropin (hCG) in women at high risk for developing ovarian hyperstimulation syndrome (OHSS). This was a retrospective cohort study of 319 women undergoing in-vitro fertilization who were at high risk for OHSS following administration of hCG for the triggering of final oocyte maturation. Patients were treated with a gonadotropin-releasing hormone agonist or antagonist protocol and were monitored for 5 days post-oocyte retrieval (early luteal phase). Severe OHSS was diagnosed in the presence of at least moderate ascites and two or more of the following: maximum ovarian diameter (MOD) > 100 mm, hematocrit (Ht)> 45%, white blood cell count (WBC) >15 000/mm3 , hydrothorax, dyspnea and oliguria. Outcome measures included change in Ht, ascites grade, WBC and MOD, as well as the association between these changes during the early luteal phase. Ascites grade, Ht and WBC increased significantly (P ≤ 0.001) during the early luteal phase, both in patients who developed and in those who did not develop severe early OHSS. MOD increased significantly (P = 0.001) only in patients who developed severe early OHSS. On multivariable analysis, both time following oocyte retrieval and whether severe early OHSS developed were significantly associated with ascites grade, Ht, WBC and MOD; furthermore, there was also a significant interaction between time and development of severe early OHSS for all four variables (P ≤ 0.001). In women at high risk of OHSS, ascites grade, Ht and WBC significantly increased with time over the 5-day observation period, in line with the pathophysiology of the syndrome. Our data support the use of MOD in the diagnosis of severe early OHSS, and provide novel evidence for the role of change in Ht as a patient-specific hemoconcentration marker during development of OHSS. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A case report on severe ovarian hyperstimulation syndrome in a pregnancy with torsion of bilateral enlarged ovaries with acute abdomen

Ovarian hyperstimulation syndrome is a complication of fertility treatment, which uses pharmacological ovarian stimulation to increase the number of oocytes and therefore embryos available during assisted reproductive technology. Ovarian hyperstimulation syndrome is invariably associated with increased volume of ovaries which is itself a threat to undergo torsion, and it may cause an additional threat requiring prompt surgical intervention in many situations. Simple release of torsion, sacrificing the devitalized ovarian tissue in part and complete can have effect in continuation of pregnancy; and something like this happened in our case. The patient, 29-year-old, a known case of polycystic ovary syndrome (PCOS), conceived through ovulation induction; came with an episode of acute pain abdomen with abdominal distension toward the later part of her first trimester. Ultrasonography was done. Bilateral enlarged ovaries of around 23 cm × 11.8 cm each were seen meeting at the pouch of Douglas with ascites. It was a case of ovarian hyperstimulation syndrome, more specifically, a case of late ovarian hyperstimulation syndrome. Serum E2 level was 3263 pg/ml. Laparotomy was then done. Intraperitoneally bilateral ovarian torsion was seen with areas of necrosis. The right oophorectomy was done, while on the left side some portion of normal ovarian tissue was preserved. Following the operation, her symptoms were improved. The pregnancy continued uneventfully. Exposure of ovaries to human chorionic gonadotropin or luteinizing hormone following controlled ovarian stimulation by follicle-stimulating hormone underlies most cases of ovarian hyperstimulation syndrome. The risk of ovarian hyperstimulation syndrome is smaller when using gonadotropin-releasing hormone antagonist (GnRH) antagonist protocol instead of GnRH agonist protocol for suppression of ovulation during ovarian hyperstimulation. To avoid ovarian hyperstimulation syndrome, the best trigger is GnRH agonists. In PCOS patients, metformin is an important aid in reducing ovarian hyperstimulation syndrome.

Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols

To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH antagonist or long GnRH agonist protocol. Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing. Fertility clinics at university hospitals. Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols. Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495 women allocated to a long GnRH agonist protocol. Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment. Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically. Women in a short GnRH antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly. NCT00756028.

Do endometriomas grow during ovarian stimulation for assisted reproduction? A three-dimensional volume analysis before and after ovarian stimulation

Whether endometriomas grow because of supraphysiological oestradiol levels attained during ovarian stimulation for assisted reproduction techniques is a concern. In this prospective study, 25 women with 28 endometriomas underwent three-dimensional ultrasound using sono-automated volume calculation software. Endometrioma volume was measured on the first day of gonadotrophin injection (V1) and the day of ovulation trigger (V2). Nine (36%) women were stimulated in a gonadotrophin releasing hormone antagonist protocol (GnRH), 13 (52%) in a long, and three (12%) in an ultra-long GnRH agonist protocol. Mean duration of stimulation was 10.3 days with median total gonadotrophin dose of 4500 IU/day. Median number of cumulus oocyte complexes was five, and metaphase-two oocytes was four. None of the endometriomas were punctured during oocyte retrieval. Median V1 was 22.2 ml (12–30 ml) and median V2 was 24.99 ml (11.2–37.4 ml) with P = 0.001. Twenty-three out of 28 endometriomas (82%) grew to some extent during ovarian stimulation. Endometrioma growth was positively correlated with prestimulation cyst volume (Correlation coefficient 0.664; P < 0.01). Although the 3-ml average growth was statistically significant, it could be regarded as clinically insignificant.

Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation.

Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation.

Pregnancy outcomes after controlled ovarian hyperstimulation in women with endometriosis-associated infertility: GnRH-agonist versus GnRH-antagonist

Background or objectiveEndometriosis is common in women referred for infertility. In vitro fertilization provides good results but the choice of the best-controlled ovarian hyperstimulation protocol remains a subject of debate. The objective of this retrospective study was to compare pregnancy outcomes in women with endometriosis-associated infertility after COH with a long agonist protocol or a six-week oral contraception-antagonist protocol. Material and methodsRetrospective analysis of a prospective database identified 284 COH cycles – 165 with GnRH-agonist protocol (GnRH-agonist group) and 119 with GnRH-antagonist protocol (GnRH-antagonist group) – in 218 women, with endometriosis from January 2013 to October 2015. ResultsNo difference in the epidemiological characteristics was found between the groups. Per started cycle, pregnancy and live-birth rates after fresh embryo transfer were higher with the GnRH-agonist protocol (25% vs. 13%, P=0.02 and 18% vs. 8%, P=0.04, respectively). Considering analysis per cycle with embryo transfer, the pregnancy rate was similar in both groups while the live-birth rate was higher in the GnRH-agonist group (29% vs. 17%, P=0.053 and 22% vs. 10%, P=0.02, respectively). No difference was observed between the groups with freeze-thaw embryo transfer. Subgroup analysis (endometrioma alone, deep infiltrating endometriosis with and without endometrioma, endometriosis with and without adenomyosis) revealed no difference between the groups for either pregnancy or live-birth rates. ConclusionA GnRH-agonist protocol appears to result in higher pregnancy and live-birth rates after fresh embryo transfer in women with endometriosis-associated infertility, suggesting that a GnRH-antagonist protocol might negatively impact endometrial receptivity.

Advanced glycation end product concentrations in follicular fluid of women undergoing IVF/ICSI with a GnRH agonist protocol

The accumulation of advanced glycation end products (AGE) is associated with ovarian dysfunction. This study examines whether the accumulation of AGE in follicular fluid affects ovarian responsiveness and embryo quality during IVF/intracytoplasmic sperm injection (IVF/ICSI) with a gonadotrophin-releasing hormone (GnRH) agonist protocol. The levels of AGE in follicular fluid were measured in 127 women undergoing IVF/ICSI in GnRH agonist cycles. Plasma hormones were also measured. Embryos were graded using standard approaches. There were inverse associations between follicular fluid AGE concentration and number of oocytes retrieved, number of fertilized oocytes, number of high-quality embryos, fertilization rate and high-quality embryo rate, adjusted for potential confounders. AGE concentration in follicular fluid was significantly higher in women with an ovarian response below the target (<7 oocytes) compared with those reaching the target (7–15 oocytes) or above the target (>15 oocytes). The cut-off value of 15.3 µg/ml for follicular fluid AGE showed 84.6% sensitivity and 55.5% specificity in evaluating the response to ovarian stimulation as below the target. The results suggest that ovarian responsiveness and embryo quality are related to intraovarian exposure to AGE.

Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis

To systematically review and summarize the existing evidence related to the effect of adenomyosis on fertility and on invitro fertilization (IVF) clinical outcomes, and to explore the effects of surgical or medical treatments. Meta-analysis. Not applicable. An electronic-based search was performed with the use of the following databases: Pubmed, Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and Google Scholar, identifying all related articles up to November 2016. We included 11 comparative studies that evaluated the clinical outcomes of IVF treatments in women with (519 patients) and without (1,535 patients) adenomyosis diagnosed with the use of magnetic resonance imaging or transvaginal ultrasound. We also separately evaluated four articles comparing fertility outcomes in two groups of infertile adenomyotic patients untreated and treated surgically or medically with the use of GnRH agonist (GnRHa). None. Primary outcome: clinical pregnancy rate after IVF. rates of implantation, ongoing pregnancy, live birth, miscarriage, and ectopic pregnancy. The summary measures were expressed as odds ratio (OR) and 95% confidence interval (CI). The rates of implantation, clinical pregnancy per cycle, clinical pregnancy per embryo transfer, ongoing pregnancy, and live birth among women with adenomyosis were significantly lower than in those without adenomyosis. The miscarriage rate in women with adenomyosis was higher than in those without adenomyosis. It appears that surgical treatment or treatment withf GnRHa increases the spontaneous pregnancy rate in women with adenomyosis. Adenomyosis has a detrimental effect on IVF clinical outcomes. Pretreatment with the use of long-term GnRHa or long protocol could be beneficial.

Predictive Value of the AMH Level and Serum Estradiol for Ovarian Hyperstimulation Syndrome in the Assisted Human Reproduction

The ovarian hyperstimulation syndrome (OHSS) is one of the major complications which occurs as a result of controlled ovarian stimulation (COS) in the assisted human reproduction. There are several factors including age, body mass index (BMI), plasma estradiol level, the anti-mullerian hormone (AMH) level and the antral follicle count (AFC), which can be used to identify the cases with high risk for this complication. The purpose of the study is to establish the predictive value of AMH for the development of OHSS before COS as well as its association with the plasma estradiol level during stimulation. The study group included 155 COS cycles using gonadotropin-releasing hormone (GnRH) agonist protocols, and analyzed the predictive value of the mentioned parameters for OHSS. The serum AMH level is superior to age and BMI for identification of patients with high risk for OHSS before starting the ovulation stimulation, and the cut-off level is 3.78ng/mlLwith 91.1% sensibility and 85.2% specificity.

GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms. The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF population, women with PCOS and women with poor ovarian response. Pre-planned subgroup analyses were performed for various antagonist treatment schedules. We included 50 studies. Of these, 34 studies reported on general IVF patients, 10 studies reported on PCOS patients and 6 studies reported on poor responders. In general IVF patients, ongoing pregnancy rate was significantly lower in the antagonist group compared with the agonist group (RR 0.89, 95% CI 0.82-0.96). In women with PCOS and in women with poor ovarian response, there was no evidence of a difference in ongoing pregnancy between the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing pregnancy rate when the oral hormonal programming pill (OHP) pretreatment was combined with a flexible protocol (RR 0.74, 95% CI 0.59-0.91) while without OHP, the RR was 0.84, 95% CI 0.71-1.0. Subgroup analysis for the fixed antagonist schedule demonstrated no evidence of a significant difference with or without OHP (RR 0.94, 95% CI 0.79-1.12 and RR 0.94, 95% CI 0.83-1.05, respectively). Antagonists resulted in significantly lower OHSS rates both in the general IVF patients and in women with PCOS (RR 0.63, 95% CI 0.50-0.81 and RR 0.53, 95% CI 0.30-0.95, respectively). No data on OHSS was available from trials in poor responders. In a general IVF population, GnRH antagonists are associated with lower ongoing pregnancy rates when compared to long protocol agonists, but also with lower OHSS rates. Within this population, antagonist treatment prevents one case of OHSS in 40 patients but results in one less ongoing pregnancy out of every 28 women treated. Thus standard use of the long GnRH agonist treatment is perhaps still the approach of choice for prevention of premature luteinization. In couples with PCOS and poor responders, GnRH antagonists do not seem to compromise ongoing pregnancy rates and are associated with less OHSS and therefore could be considered as standard treatment.

Follicular sensitivity index (FSI): a novel tool to predict clinical pregnancy rate in IVF/ICSI cycles.

This study aims to introduce a new tool (the Follicular Sensitivity Index; FSI) for objective assessment of follicular responsiveness to exogenous gonadotropins and to evaluate its ability to predict the clinical pregnancy rate in women with unexplained infertility or tubal factor undergoing IVF/ICSI. FSI was calculated as preovulatory follicle count (PFC)×100,000/[antral follicle count (AFC)×total received FSH doses]. One thousand women were included and were divided according to the FSI tertile values into three groups. The primary outcome was clinical pregnancy defined by the presence of an intrauterine gestational sac 5weeks after embryo transfer. There was progressive increase in the clinical pregnancy rate from the low to the high FSI groups (0.27±0.4 vs 0.4±0.4 and 0.58±0.4; p<0.001). Receiver operator curves showed that FSI had a greater area under the curve than those of the AFC, PFC, and the FSH dose (0.638 vs 0.509, 0.538, and 0.589 respectively). Multivariate logistic regression analysis showed that the correlation between FSI and pregnancy was independent of potential confounding factors like age and body mass index (p<0.001). FSI can predict the clinical pregnancy rate in women with unexplained infertility or tubal factor undergoing IVF/ICSI using GnRH agonist protocol. Higher FSI values had significantly higher oocyte yield and fertilization and clinical pregnancy rates. Wider implications of these findings include the potential use of FSI to define absolute criteria of poor/good ovarian response in IVF/ICSI cycles, guide future IVF cycle management for the same couples, and guide cycle cancelation criteria for poor ovarian response.

Predictive Value of the AMH Level and Serum Estradiol for Ovarian Hyperstimulation Syndrome in the Assisted Human Reproduction

The ovarian hyperstimulation syndrome (OHSS) is one of the major complications which occurs as a result of controlled ovarian stimulation (COS) in the assisted human reproduction. There are several factors including age, body mass index (BMI), plasma estradiol level, the anti-mullerian hormone (AMH) level and the antral follicle count (AFC), which can be used to identify the cases with high risk for this complication. The purpose of the study is to establish the predictive value of AMH for the development of OHSS before COS as well as its association with the plasma estradiol level during stimulation. The study group included 155 COS cycles using gonadotropin-releasing hormone (GnRH) agonist protocols, and analyzed the predictive value of the mentioned parameters for OHSS. The serum AMH level is superior to age and BMI for identification of patients with high risk for OHSS before starting the ovulation stimulation, and the cut-off level is 3.78ng/mL with 91.1% sensibility and 85.2% specificity.

Predicting the outcome of different protocols of invitro fertilization with anti-Muüllerian hormone levels in patients with polycystic ovary syndrome.

ObjectiveThis study evaluated associations of basal serum and follicular fluid (FF) anti-Muüllerian hormone (AMH) levels with in vitro fertilization (IVF) outcomes in polycystic ovary syndrome (PCOS) patients.MethodsThis prospective study included 179 consecutive women undergoing IVF, including 59 with PCOS and non-PCOS controls. Thirty PCOS cases had long gona-dotrophin-releasing hormone agonist (GnRH-a) and 29 had antagonist (GnRH-ant) protocols. Controls underwent conventional GnRH-a. Associations of basal serum and FF AMH levels with IVF outcomes were assessed.ResultsMedian serum and FF AMH levels, antral follicle count (AFC), oestradiol human chorionic gonadotropin injection day (peak E2), and retrieved oocyte numbers were higher in PCOS patients than in controls (all P < 0.01). Oocyte maturation and high-quality embryo rates were lower in PCOS patients than in controls (P < 0.01), but both groups had similar fertilization, implantation, clinical pregnancy, and newborn rates. Peak E2 was higher in GnRH-ant than in GnRH-a protocols (16.5 nmol/L vs. 12.1 nmol/L, P < 0.05). AMH levels were correlated with AFC in PCOS patients (P < 0.01). Peak E2 and FF AMH levels were independent predictors of oocyte number. Peak E2 predicted the fertilization rate.ConclusionSerum basal AMH levels are predictive of oocyte quantity, but not oocyte quality or IVF outcomes. Serum AMH, FF AMH, and outcomes are similar among protocols.

A randomized controlled trial comparing the efficacy and safety of two HMG preparations gaining their LH bioactivity from different HCG sources

In this prospective, controlled, randomized, multicentre, non-inferiority study, efficacy and safety of two HMG preparations (Menopur®- Ferring and Meriofert®- IBSA Institut Biochimique SA) for ovarian stimulation were compared (270 women undergoing IVF aged between 18 and 39 years; BMI 30 kg/m2 or less; less than three prior completed assisted reproduction technique cycles). A standard long down-regulation with gonadotrophin-releasing hormone agonist protocol, with HCG triggering was used; primary end-point was total number of oocytes retrieved; attention was paid toovarian hyperstimulation syndrome (OHSS). No statistically significant differences between the treatment groups were reported for most of the clinically significant end-points, including embryo quality, fertilization rate, implantation rate, ongoing pregnancy rate and live birth rate. Total number of oocytes retrieved was higher in the new HMG group compared with the reference (11.6 ± 6.6 and 9.7 ± 5.9, respectively, with a 95% CI of the difference equal +0.43 to +3.43). Increased number of oocytes was obtained through a shorter stimulation, but HMG units per oocyte retrieved were equivalent. The safety profile of the products for frequency of ovarian hyperstimulation syndrome was the same. This study showed that the new HMG preparation is a viable alternative for conducting ovarian stimulation in IVF cycles.

Oxidative Stress Markers in GnRH Agonist and Antagonist Protocols in IVF.

SummaryBackgroundOur aim was to study the effect of GnRH agonist and antagonist protocols of ovarian stimulation on oxidative stress parameters in serum and the influence of oxidative stress parameters change on the outcome of IVF cycles.MethodsThis prospective study included 82 patients who underwent IVF procedures. We determined SOD, MDA and SH groups in serum. Serum samples were obtained between the second and fourth day of the cycle and on the day of HCG administration during ovarian stimulation.ResultsPatients were divided into two groups depending on the protocol of stimulation. The mean total and mature oocytes number and number of fertilized oocytes were higher in GnRH agonist group. There was no significant difference in biochemical pregnancy, miscarriage and live–birth rate in both groups. Mean serum SOD was significantly lower, while mean serum MDA and SH groups were significantly higher after ovarian stimulation. Delivery rate was higher in patients without OS while miscarriage rate was higher in patients with OS.ConclusionsOur study confirmed that there is a difference in the concentration of oxidative stress parameters before and after ovarian stimulation. IVF outcome is better in patients without OS after ovarian stimulation. However, the protocol of ovarian stimulation is neither associated with a change in oxidative stress parameters nor with the outcome of ART procedures.

Comparison of GnRH antagonist and agonist mini-dose long protocols in infertile cases undergoing controlled ovarian hyperstimulation

The purpose of the present study was to determine if there is a difference between multi-dose gonadotropin releasing hormone (GnRH) antagonist protocol and long GnRH agonist protocol. This retrospective study compared the data pertaining to patients chosen as per predetermined acceptance criteria, 113 of whom were administered multi-dose antagonist protocol for controlled ovarian hyperstimulation (COH) while 133 were administered long agonist protocol for COH at Suleymaniye Teaching Hospital of Obstetrics and Gynecology. While cancellation rate was found to be significantly higher in antagonist group (17.7% vs 11.28%), the number of follicles > 14 mm and > 16 mm, E2 level, and the number of retrieved oocytes on the day of hCG trigger were significantly lower in the same group. However, there was no difference between fertilization rates and embryonic development rates. The pregnancy rates per transfer and per cycle were found to be 40.9% and 31.7%, respectively; in the antagonist group they were lower, though not significantly, when compared to agonist group (44.1% and 39.1%, respectively). Ongoing pregnancy rates were found to be similar between the groups. GnRH antagonist treatment protocol has a level of efficacy similar to agonist treatment protocol in terms of pregnancy results for all groups.

The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial.

Does the addition of anti-Müllerian hormone (AMH) to a conventional dosage regimen, including age, antral follicle count (AFC) and BMI, improve the rate of targeted ovarian response, defined as 5-12 oocytes after IVF? The addition of AMH did not alter the rate of targeted ovarian response, 5-12 oocytes, or decreased the rate of ovarian hyperstimulation syndrome (OHSS) or cancelled cycles due to poor ovarian response. Controlled ovarian hyperstimulation (COH) in connection with IVF is sometimes associated with poor ovarian response resulting in low pregnancy and live birth rates or leading to cycle cancellations, but also associated with excessive ovarian response, causing an increased risk of OHSS. Even though it is well-established that both AMH and AFC are strong predictors of ovarian response in IVF, few randomized trials have investigated their impact on achieving an optimal number of oocytes. Between January 2013 and May 2016, 308 patients starting their first IVF treatment were randomly assigned, using a computerized randomization program with concealed allocation of patients and in the proportions of 1:1, to one of two dosage algorithms for decisions on hormone starting dose, an algorithm, including AMH, AFC, age and BMI (intervention group), or an algorithm, including only AFC, age and BMI (control group). The study was blinded to patients and treating physicians. Women aged >18 and <40 years, with a BMI above 18.0 and below 35.0 kg/m2 starting their first IVF cycle where standard IVF was planned, were eligible. All patients were treated with a GnRH agonist protocol and recombinant FSH was used for stimulation. The study was performed as a single-centre study at a large IVF unit at a university hospital. The rate of patients having the targeted number of oocytes retrieved was 81/152 (53.3%) in the intervention group versus 96/155 (61.9%) in the control group (P = 0.16, difference: -8.6, 95% CI: -20.3; 3.0). Cycles with poor response (<5 oocytes) were more frequent in the AMH group, 39/152 (25.7%) versus the non-AMH group, 17/155 (11.0%) (P < 0.01), while the number of cancelled cycles due to poor ovarian response did not differ 7/152 (4.6%) and 4/155 (2.6%) (P = 0.52). An excessive response (>12 oocytes) was seen in 32/152 (21.1%) and 42/155 (27.1%) patients, respectively (P = 0.27). Moderate or severe OHSS was observed among 5/152 (3.3%) and 6/155 (3.9%) patients, respectively (P = 1.0). Live birth rates were 48/152 (31.6%) and 42/155 (27.1%) per started cycle. The categorization of AMH values in predicted low, normal and high responders was originally established using the Diagnostic Systems Laboratories assay and was translated to more recently released assays, lacking international standards and well-established reference intervals. The interpretation of AMH values between different assays should therefore be made with some caution. An individualised dosage regimen including AMH compared with a non-AMH dosage regimen in an unselected patient population did not alter the number of women achieving the targeted number of oocytes, or the cancellation rate due to poor response or the occurrence of moderate/severe OHSS. However, this study cannot answer the question if using an algorithm for dose decision of FSH is superior to a standard dose and neither which ovarian reserve test is the most effective. Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and unrestricted grants from Ferring Pharmaceuticals and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest. The study was registered at www.clinicaltrials.gov NCT02013973. 6 December 2013. 14 January 2013.