Agonist Protocol Research Articles

Effect of aromatase inhibitor (letrozole) with long agonist protocol on the results of ICSI/ET in females with minimal and mild endometriosis

BackgroundICSI/ET in endometriosis patients has poor outcome by traditional protocols. The key enzyme in the biosynthesis of estradiol, aromatase, has been demonstrated within endometriosis. Combined administration of aromatase inhibitor and GnRH-agonist may efficiently suppress estrogen biosynthesis through a combined pituitary, ovarian and local factors in the implants. ObjectiveEvaluate the effect of using letrozole in improvement of the results of ICSI/ET in endometriosis women with long agonist protocol. PatientsSixty infertile women with minimal and mild endometriosis according to the revised American Fertility Society classification were scheduled for ICSI/ET. MethodsWomen were randomized into two groups. Group 1: using the traditional luteal long agonist protocol using triptorelin 0.1 and Group 2: using letrozole 5mg/day started 5days after the start of GnRH agonist for 5days. All patients were monitored with day 6 serum estradiol level and estradiol at day of HCG. The number of days of stimulation, number of retrieved oocytes, number of MII oocytes, cleavage rate, and pregnancy rate were studied in both groups. ResultsDays of stimulation were significantly higher in the treated group (p=0.019). Oocytes number was not affected (10.57±6.14) and (11.21±6.41) (p=0.516) in groups 1 and 2 respectively also, the number of embryos was not affected (p=0.955). Nine (32.1%) pregnant cases of 28 were in the first group while 8 from 27 in the second group (29.6%). ConclusionLetrozole significantly affected days of stimulation of ICSI cycle in endometriosis patients without affecting pregnancy rate.

IVF/ICSI outcomes of the OCP plus GnRH agonist protocol versus the OCP plus GnRH antagonist fixed protocol in women with PCOS: a randomized trial

To compare the IVF/ICSI outcomes of the long GnRH agonist and the fixed GnRH antagonist protocol in women with PCOS. Randomized controlled trial. Baskent University Department of Obstetrics and Gynecology. Three hundred women with PCOS. IVF/ICSI following the long GnRH agonist down-regulation or the fixed GnRH antagonist protocols. Ongoing pregnancy rates. Ongoing pregnancy rates were 36.4% in the OCP+GnRH agonist group and 35.9% in the OCP+GnRH antagonist group (p>0.05). Progesterone levels on the day of hCG (0.76±0.71 vs. 0.58±0.50), endometrial thickness on the day of hCG (11.57±2.50 vs. 10.50±2.01), total gonadotropin used (1388.71±482.39 vs. 1253.25±415.81), and duration of COH (9.07±1.96 vs. 8.39±1.75) were significantly lower in the OCP+GnRH antagonist group. The OCP+long GnRH agonist and the OCP+fixed GnRH antagonist protocols yield similar ongoing pregnancy rates in women with PCOS. Although this study consisting three hundred patients, seems to be large enough in a single center, we were not able to reach to the actual size of power analysis which was approximately 3,000.

Subfertility in women with familial Mediterranean fever

The aim of this study was to examine the causes and different modalities used for management of subfertile patients with familial Mediterranean fever (FMF). The study comprised of 74 infertile women with FMF. All patients were diagnosed as having FMF. All patients underwent a full infertility work-up. They were scheduled to expectant treatment, ovulation induction and timed intercourse, intrauterine insemination or intracytoplasmic sperm injection. Anovulation was reported in 18 patients (24.32%). Anovulation was due to polycystic ovary syndrome in 12 (16.22%) cases and due to other causes in six patients (8.11%). Excessive clear peritoneal fluid was present in 56 (57.67%) and male-factor infertility was present in 14 couples (18.91%). Ovulation induction and timed intercourse was adopted for a maximum of six cycles and intrauterine insemination for three cycles. In vitro fertilization/intracytoplasmic sperm injection was needed in six cases using standard long agonist protocol. Twenty-six women became pregnant. The causes of infertility in patients with FMF are not different from those expected in the general population. Treatment of the problem should be causal, adopting the conventional lines of treatment up to in vitro fertilization/intracytoplasmic sperm injection when appropriate. Colchicine is the treatment of choice and it is important to use it in its proper doses to control the disease.

Can cabergoline prevent ovarian hyperstimulation syndrome in polycystic ovarian patients undergoing gonadotropin stimulation?

Can cabergoline prevent ovarian hyperstimulation syndrome in polycystic ovarian patients undergoing gonadotropin stimulation?

GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology

BackgroundThe selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation.MethodsA total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed.ResultsOut of a total of 681 oocytes, 189 (27.8 %) were morphologically normal, 220 (32.3 %) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist-treated groups (P ≫ 0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups (P ≫ 0.05).ConclusionsOur randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.

Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles

To investigate the relationship between serum P levels on the day of hCG administration and pregnancy outcomes in different responders undergoing IVF. Retrospective study. Teaching hospital. A total of 11,055 women who underwent their first IVF/intracytoplasmic sperm injection cycles and a subgroup of 4,021 women undergoing frozen-embryo transfer (FET) cycles. Patients underwent IVF-ET with the long GnRH agonist protocol. The ovarian response was classified as high (≥ 20 oocytes; n = 2,023), poor (≤ 4 oocytes; n = 827), or intermediate (remaining cases; n = 8,205) according to the number of oocytes retrieved. Clinical outcomes of IVF-ET and FET cycles were analyzed according to plasma P levels. Ongoing pregnancy rates (PRs). Ongoing PRs in fresh cycle were inversely associated with serum P levels on the day of hCG administration for all patients. Different P threshold concentrations were determined according to different ovarian response: We proposed a serum P level of 1.5 ng/mL as the threshold for poor responders, 1.75 ng/mL for intermediate responders, and 2.25 ng/mL for high responders. Our study does not show negative results for elevated P levels on oocyte performance in terms of fertilization, cleavage rate, or PR of FET cycles within different ovarian responses, offering no evidence for a detrimental effect of high P on oocyte quality. Elevated P levels on the day of hCG administration negatively influence PR regardless of different ovarian responses, although increased P threshold concentration is associated with better ovarian responses. The detrimental effect of P elevation on PR seems to be unrelated to oocyte quality in all responders.

The value of anti-Mullerian hormone measurement in the long GnRH agonist protocol: association with ovarian response and gonadotrophin-dose adjustments

BACKGROUNDThis study evaluated the predictive value of serum and follicular fluid (FF) concentrations of anti-Müllerian hormone (AMH) with respect to treatment outcome variables in an IVF cycle.METHODSA retrospective analysis was performed with data from 731 normogonadotrophic women undergoing controlled ovarian stimulation after stimulation with highly purified menotrophin (HP-hMG) or rFSH following a long GnRH agonist protocol.RESULTSIn both treatment groups, the serum AMH concentration at the start of the stimulation was significantly (P < 0.001) positively correlated with the serum levels of estradiol (HP-hMG: r = 0.45; rFSH: r = 0.55), androstenedione (HP-hMG: r = 0.50; rFSH: 0.49) and total testosterone (HP-hMG: r = 0.40; rFSH: r = 0.36) at the end of the stimulation as well as the number of oocytes retrieved (HP-hMG: r = 0.48; rFSH: r = 0.62), the AMH concentration in FF (HP-hMG: r = 0.55; rFSH: 0.61) and the serum progesterone concentration (HP-hMG: r = 0.39; rFSH: r = 0.50) at oocyte retrieval. For both treatments, serum AMH at the start of the stimulation was a good predictor of the need to increase or decrease the gonadotrophin dose on stimulation day 6 and of ovarian response below (<7 oocytes) or above (>15 oocytes) the target. No significant relationships were observed between serum AMH and embryo quality or ongoing pregnancy.CONCLUSIONThe serum AMH concentration at the start of the stimulation in IVF patients down-regulated with GnRH agonist in the long protocol revealed a positive relationship with ovarian response to gonadotrophins in terms of oocytes retrieved and accompanying endocrine response. AMH is a good predictor of the need for gonadotrophin-dose adjustment on stimulation day 6 for patients with a fixed starting dose, but a poor predictor of embryo quality and pregnancy chances in individual patients.

A randomized controlled trial of the GnRH antagonist ganirelix in Chinese normal responders: high efficacy and pregnancy rates

Gonadotropin-releasing hormone (GnRH) antagonists for controlled ovarian stimulation (COS) were only recently introduced into China. The efficacy and safety of the GnRH antagonist ganirelix was assessed in a multicenter, controlled, open-label study, in which Chinese women were randomized to either ganirelix (n = 113) or a long GnRH agonist protocol of triptorelin (n = 120). The primary end point was the amount of recombinant follicle-stimulating hormone (rFSH) required to meet the human chorionic gonadotropin criterion (three follicles ≥17 mm). The amount of rFSH needed was significantly lower for ganirelix (1272 IU) vs. triptorelin (1416 IU; P< 0.001). Ongoing pregnancy rates per started cycle were 39.8% (ganirelix) and 39.2% (triptorelin). Although both treatments were well tolerated, cancellation due to risk of ovarian hyperstimulation syndrome (OHSS) was less frequent with ganirelix (1.8%) than triptorelin (7.5%) (P = 0.06). Less rFSH was needed in the ganirelix protocol than the long GnRH agonist protocol, with fewer reported cases of OHSS and similar pregnancy rates.

Outcome of in vitro fertilization following stimulation with highly purified hMG or recombinant FSH in downregulated women of advanced reproductive age: a prospective, randomized and controlled trial

Objective: To compare highly purified human menopausal gonadotropin (HP-hMG) with recombinant follicle-stimulating hormone (rFSH) on ovarian response and pregnancy outcome in downregulated women of advanced reproductive age. Design: A prospective, randomized and controlled study of 127 consecutive normogonadotropic infertile women ≥35 years old undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycles received ovarian stimulation with HP-hMG (n = 63) or with rFSH (n = 64) in a long gonadotropin-releasing hormone agonist protocol. Results: More leading (≥18 mm) follicles and oocytes were obtained in rFSH group (p = 0.008 and p < 0.001, respectively). The proportion of top-quality embryo from oocyte retrieval and live birth rate per started cycle trended towards improvement with HP-hMG (OR 1.3, 95% CI 0.9–1.8; OR 1.9, 95% CI 0.9–3.9; respectively), although they were not significant difference between two groups. At end of stimulation, higher serum progesterone level was found in rFSH group (p < 0.001). Conclusion: Following downregulated women of advanced reproductive age, superiority of HP-hMG over rFSH in live birth rate could not be concluded from this study, but noninferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality and endocrine response exist between HP-hMG and rFSH, which may be relevant to treatment outcome.

Using a half dose of leuplin depot in a long-term protocol for in vitro fertilization

A retrospective review of medical charts was used to compare the use of a half dose of leuplin depot (3.75 mg/vial; Takeda, Osaka, Japan) in a long agonist protocol for in vitro fertilization (IVF) (long protocol) with the conventional pillleupron-HMG/FSH short agonist protocol (short protocol). From January 2008 through December 2010, our unit completed 108 IVF case cycles (Table 1). The major variation between cases is the protocol for ovulation stimulation. The same personnel used the fixed protocol to perform oocyte retrieval, fertilization, in vitro culture, and embryo transfer. In the long, half-dose depot protocol (long protocol), a half dose of leuplin depot was given during menstruation. Then, we started 150e225 IU HMG (Menopur, Ferring GmbH, Kiel, Germany)/FSH (Puregon, Merck Serono, Modugno, Italy) on a Thursday 3e4 weeks later. Ovulation was induced with a 10,000 IU sHCG (5000 IU Pregnnyl; Organon, Oss, Holland) i.m. injection when the two leading follicles were 16 mm above. Oocyte retrieval was performed 34e39 hours later. We performed fixed-length (6 cm) embryo transfer 3 days after oocyte retrieval. For luteal support after oocyte retrieval, we administered 4 mg/day estrade (2 mg estradiol valerate; Synmosa, Taipei, Taiwan) and crinone 8% vaginal gel (Merck Senoro). Additionally, 1500 IU HCG was administered at D3, D6, and D9. A urine pregnancy test was administered 14 days later. If the pregnancy test was positive, a vaginosonogram was performed 2 weeks later. We defined clinical pregnancy as the observation of a gestational sac inside the uterine cavity on the vaginosonogram. In our cases series, the cases that were administered the long protocol achieved a relatively higher pregnancy rate, although it was not statistically significant (39.28% for patients administered the long protocol vs. 28.75% for patients administered the short protocol; 31.48% total pregnancy rate; p1⁄4 0.071).

Combination of recombinant follicle stimulating hormone with human menopausal gonadotrophin or recombinant luteinizing hormone in a long gonadotrophin-releasing hormone agonist protocol: a retrospective study.

To assess the effect of supplementation with recombinant human luteinizing hormone (rhLH) for patients treated either with recombinant follicle stimulating hormone (rFSH) plus rhLH or with rFSH plus human menopausal gonadotrophin (HMG) in a long gonadotrophin-releasing hormone (GnRH) agonist-stimulation protocol. A single-centre, retrospective analysis of patients with hypo responsiveness to a long GnRH agonist protocol (n = 174), with consecutive in-vitro fertilization or intracytoplasmic sperm injection cycles, compared the outcomes of long luteal GnRH agonist ovarian stimulation using rFSH combined with HMG (n = 100) versus rFSH combined with rhLH (n = 74). The endpoints included clinical pregnancy, number of oocytes retrieved, and total gonadotrophin dose. Significantly more clinical pregnancies were achieved after stimulation with rFSH and rhLH than after stimulation with rFSH and HMG (35.1 vs. 19%, p < 0.01). More oocytes were recovered (13.1 vs. 11.3, p = 0.024) with less FSH utilized in the rFSH and rhLH group than in the rFSH and HMG group (2706.4 vs. 4134.2 U, p < 0.001). Use of rFSH combined with rhLH in long GnRH agonist assisted reproductive technology (ART) cycles was associated with more clinical pregnancies, recovery of more oocytes, and reduction in gonadotrophin use, suggesting that the superior purity and consistency of rFSH and rhLH may result in better clinical outcomes.

Étude prospective randomisée protocoles agonistes long versus court chez les patientes mauvaises répondeuses en fécondation in vitro

ObjectivesDifferent ovarian stimulation protocols are used for in vitro fertilization (IVF) in “poor responder” patients. Our work aims at comparing two ovarian stimulation protocols (long agonist half-dose protocol versus short agonist protocol without pretreatment) in this population of women. Patients and methodsThis prospective, randomized study was realized at the University Hospital of Saint-Étienne and concerns “poor responder” patients (age between 38 and 42years and FSH at day 3 more than 9.5IU/L; and/or antral follicles count less or equal to 6; and/or failure of previous stimulation). The primary endpoint is based on the number of oocytes retrieved at the end of an IVF cycle. ResultsOut of the 44 patients randomized, 39 cycles were taken into account (20 in the long protocol, 19 in the short one). At the end of the stimulation (FSH-r 300 to 450UI/d), the number of follicles recruited appears higher in the long protocol but the difference is not significant (diameter between 14 and 18mm: 3.0±2.31 vs 1.88±1.89 and diameter greater than 18mm: 3.9±2 85 vs 3.06±2.77). The same tendency is observed for all the following criteria: the number of retrieved oocytes (6.74±2.73 vs 6.38±4.26), the total number of embryos (3.16±2.03 vs 2.25±2.11), the pregnancy rate per retrieval (21% vs 19%) and per cycle (20% vs 16%), and the number of children born alive. Discussion and conclusionThe study did not reveal any difference between the two protocols but the long half-dose seems to be better.

Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles

This study analysed the relationship between serum progesterone/oestradiol concentrations and IVF pregnancy outcomes in gonadotrophin-releasing hormone agonist protocols. A total of 2921 infertile women undergoing IVF were assigned to four groups according to serum progesterone and oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration: group 1 (control) progesterone<3.34nmol/l and oestradiol<19,124pmol/l; group 2 (high oestradiol); group 3 (high progesterone); group 4 (high progesterone and high oestradiol). Compared with group 1, group 4 had lower clinical pregnancy and live birth rates as well as the highest ectopic pregnancy rate (29.15% versus 45.91%; 18.67% versus 34.34%; 18.10% versus 5.82%; P<0.05). Group 3 had lower clinical pregnancy and live birth rates per embryo-transfer cycle (29.78% versus 45.91%; 20.28% versus 34.34%, respectively; P<0.05). Clinical pregnancy rates were similar in frozen–thawed embryo transfers (FET) among the four groups. In conclusion, elevated progesterone was detrimental to live birth rates. High serum oestradiol concentration on HCG day did not affect the IVF pregnancy outcome. In combination with the elevated progesterone, high oestradiol concentrations had a potential negative effect. For these patients, FET should be suggested to improve the pregnancy outcomes.The aim of this study was to analyse the relationship between serum progesterone/oestradiol concentrations and IVF pregnancy outcomes in gonadotrophin-releasing hormone agonist protocols. A total of 2921 infertile women undergoing IVF were assigned to four groups according to their serum progesterone and oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration: group 1 (control) progesterone<3.34nmol/l and oestradiol<19,124pmol/l; group 2 (high oestradiol); group 3 (high progesterone); group 4 (high progesterone and high oestradiol). Compared with group 1, patients in group 4 had lower clinical pregnancy (29.15% versus 45.91%) and live birth rates (18.67% versus 34.34%) as well as the highest ectopic pregnancy rate (18.1% versus 5.82%) (all P<0.05). Those in group 3 had lower clinical pregnancy and live birth rates per embryo transfer cycle (29.78% versus 45.91%; 20.28% versus 34.34%, respectively, P<0.05). Embryo quality appeared to be unaffected since similar clinical pregnancy rates in frozen–thawed embryo transfer (FET) cycles among the four groups. In conclusion, elevated progesterone was detrimental to live birth rates. A high serum oestradiol concentration on the day of HCG administration did not affect the IVF pregnancy outcome. In combination with the elevated progesterone and oestradiol concentrations had a potential negative effect. For these patients, FET should be suggested to improve the pregnancy outcomes.

Comparison of GnRH antagonist versus GnRH agonist protocol in poor ovarian responders undergoing IVF

Comparison of GnRH antagonist versus GnRH agonist protocol in poor ovarian responders undergoing IVF

Agonist and antagonist coast

The use of GnRH-a in ovarian stimulation permitted stronger stimulation resulting in an increased incidence of OHSS. The first Cochrane review comparing GnRH agonist and GnRH antagonist protocols for ovarian stimulation showed no significant difference in OHSS rate between the two protocols, however, a recent Cochrane review showed a highly significant decrease in the incidence in OHSS rate in the antagonist protocol. Coasting is a commonly used procedure for preventions of OHSS. The optimum time to start coasting is when the lead follicle reaches 16 mm in diameter and hCG should be given when E2 level drops below 3000 pg/ml. Coasting may act by diminishing the functioning granulosa cell cohort. Administration of daily GnRH antagonist in high risk patients for OHSS who were down-regulated by GnRH-a resulted in rapid drop of E2 and decrease in incidence of OHSS. A series of patients who developed early OHSS were treated by daily GnRH antagonist injections, all embryos were cryopreserved. No progression to severe OHSS was observed.

A prospective study of GnRH long agonist versus flexible GnRH antagonist protocol in PCOS: Indian experience

BACKGROUND:Polycystic ovarian syndrome is a common endocrine disorder of reproductive age women. Many controlled ovarian stimulation (COS) strategies have been offered for the treatment of patients with PCOS undergoing in vitro fertilization, but the optimal protocol is still a controversy. There is no compelling evidence for the advantage of one stimulation protocol over the other.MATERIALS AND METHODS:This is a single-center prospective controlled study comparing long agonist and antagonist protocol in PCOS women.RESULTS:There was no significant difference in live birth rate and clinical pregnancy rate. Rate of ovarian hyperstimulation syndrome was significantly higher in the agonist group. Number of oocytes retrieved, number of follicles and peak estradiol levels were significantly more in the agonist group.CONCLUSION:The GnRH antagonist protocol is an equally effective but safer protocol in PCOS patients compared with the long agonist protocol.

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET)

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Comparison of anti-mullerian hormone and antral follicle count for assessment of ovarian reserve

AIM:This study aims to compare the efficacy of AFC and AMH, as markers for ovarian reserve.MATERIALS AND METHODS:75 patients with PCO (polycystic ovaries) undergoing IVF were randomized with 75 non-PCO patients. On day 3, volume of ovary was acquired, ovarian volume was defined by VOCAL, and Sono AVC was used to count the number of antral follicles. Sum total of antral follicles in both ovaries was taken as total antral follicle count (AFC). AMH was measured on the same day. Long agonist protocol with recombinant FSH (rFSH) was used for IVF stimulation till at least two follicles of 18 mm were seen. hCG 10,000 iu was given and ovum pick up was done after 34-35 h. Primary end point was number of follicles >12 mm seen on day of hCG. Final end point was number of ova retrieved on ovum pick up. Correlation of AFC and AMH was checked for both end points and with each other.RESULTS:Correlation of AFC and follicles >12 mm on day of hCG in PCO group is 0.56 and non-PCO group is 0.63,1 and for AMH and follicles >12 mm on day of hCG in PCO group is 0.42 and non-PCO group is 0.47. Correlation of AFC with number of ova retrieved on OPU in PCO group is 0.44 and for non-PCO group is 0.50. The value for AMH is 0.39 in PCO and 0.43 for non-PCO group. Comparing correlation of AFC and AMH for primary end point in PCO group has ‘z’ value 1.11(onetailed significance 0.1335, twotailed significance 0.267) and in non-PCO group comparison shows a ‘z’ value of 1.39 (one tailed significance 0.0823, two-tailed significance 0.1645). Therefore in both groups, AFC and AMH correlates with total number of follicles >12 mm on day of hCG, but both AFC and AMH have independent significance. Comparing correlation of AFC and AMH with number of ova retrieved on OPU, in non-PCO group has ‘z’ value of 0.54(one tailed 0.2946, two-tailed 0. 5892). In PCO group, this comparison shows, ‘z’ value of 0.36(one tailed 0.3594, two tailed 0.7188).CONCLUSION:AFC and AMH correlate with each other but have independent significance for estimating follicles >12 mm on day of hCG. For ova retrieved on OPU, in PCO group, AMH and AFC have similar significance. In non-PCO, AMH may increase accuracy of estimation of number of ova retrieved on OPU over AFC, but difference is not significant. AFC only may suffice for estimation of number of ova retrieved on OPU for all practical purposes.

Anti-mullerian hormone cut-off values for predicting poor ovarian response to exogenous ovarian stimulation in in-vitro fertilization

OBJECTIVES:(a) To establish the cut-off levels for anti-Mullerian hormone (AMH) in a population of Indian women that would determine poor response. (b) To determine which among the three ie.,: age, follicle stimulating hormone (FSH), or AMH, is the better determinant of ovarian reserve.STUDY DESIGN:Prospective observational study.SETTING:In vitro fertilization (IVF) unit of a tertiary hospital.MATERIALS AND METHODS:The inclusion criterion was all women who presented to the center for in-vitro fertilization/Intracytoplasmic sperm injection (IVF/ICSI). The exclusion criteria were age >45 years, major medical illnesses precluding IVF or pregnancy, FSH more than 20 IU/L, and failure to obtain consent. The interventions including baseline pelvic scan, day 2/3 FSH, luteinizing hormone (LH), estradiol estimations, and AMH measurement on any random day of cycle were done. Subjects underwent IVF according to long agonist or antagonist protocol regimen. Oocyte recovery was correlated with studied variables. The primary outcome measure was the number of oocytes aspirated (OCR). Three categories of ovarian response were defined: poor response, OCR ≤ 3; average response, OCR between 4 and 15; hyperresponse, OCR > 15.RESULTS:Of the 198 patients enrolled, poor, average, and hyperresponse were observed in 23%, 63%, and 14% respectively. Correlation coefficient for AMH with ovarian response was r = 0.591. Area under the curve (AUCs) for poor response for AMH, subject's age, and FSH were 0.768, 0.624, and 0.635, respectively. The discriminatory level of AMH for prediction of absolute poor response was 2 pmoL/l, with 98% specificity and 20% sensitivity.CONCLUSIONS:AMH fares better than age and FSH in predicting the overall ovarian response and poor response, though it cannot be the absolute predictor of non-responder status. A level of 2 pmol/l is discriminatory for poor response.

Comparison between GnRH agonist and antagonist protocols for severe endometriosis in assisted reproductive cycles

Purpose Endometriosis may influence different aspects of reproductive physiology including folliculogenesis, ovulation, embryo quality, and fertilization. Recent data demonstrate that patients with endometriosis-associated infertility undergoing in vitro fertilization (IVF) have a reduction of pregnancy rates compared to women with other indications for IVF. The aim of the study is to evaluate the outcomes of IVF after controlled ovarian hyperstimulation (COH) with GnRH antagonist (GnRH-ant) or GnRH agonist (GnRH-a) in severe endometriosis patients. Methods A total of 101 patients with severe endometriosis undergoing IVF cycles were retrospectively enrolled into two groups in relation to hypothalamic inhibition before COH, obtained respectively with leuprorelin and cetrorelix. We evaluated characteristics of COH and clinical outcomes (overall pregnancy rate, implantation rate, spontaneous miscarriages, ectopic pregnancies, and clinical pregnancy rates). Results The group treated with GnRH-ant presented a similar number of MII oocytes and good quality embryos while using a lower amount of gonadotropins. Outcomes of COH with both GnRH-ant and GnRH-a were similar in patients with stage III-IV endometriosis. The number of retrieved oocytes, the number of obtained embryos, the implantation rates, and the clinical pregnancy rates were similar with GnRH-ant and GnRH-a protocols. Conclusions Considering the pregnancy outcomes, COH with both GnRH-ant and GnRH-a protocols do not present statistical differences in patients with severe endometriosis, but the GnRH-ant protocol could be more convenient in term of gonadotropins amount and patient discomfort.