Effectiveness of GnRH antagonist in intrauterine insemination cycles

Objective

To evaluate the effectiveness of GnRH antagonists in women undergoing controlled ovarian stimulation and intrauterine insemination cycles (COS/IUI).

Study design

Randomized controlled trial. Recruited women were randomized into two groups: GnRH antagonist and control group. The primary outcomes were incidence of premature LH surge and clinical pregnancy rates.

Results

One hundred and forty-one consecutive women were included in the study, with 70 in the antagonist group and 71 in the control arm. The baseline clinical characteristics were similar in both groups. The incidence of premature LH surge and premature luteinization was lower in the antagonist group as compared to the control group (5% vs. 10.3%, P = 0.45 and 5% vs. 13.8, P = 0.31) but not statistically significant. The clinical pregnancy rates were lower in the antagonist group (2.8% vs. 10%, P = 0.12), which was also not statistically significant.

Conclusion

The addition of GnRH antagonist during controlled ovarian stimulation and intrauterine insemination cycles does not lead to improvement in clinical pregnancy rates.     

Conversion of high-response gonadotropin intrauterine insemination cycles to in vitro fertilization results in excellent ongoing pregnancy rates

OBJECTIVE: To determine whether conversion of gonadotropin/IUI cycles at high risk of high-order multiple pregnancies to IVF yields a pregnancy rate high enough to warrant the added intervention. DESIGN: Case-control study. SETTING: Brigham and Women's Hospital assisted reproductive technology program. PATIENT(S): Seventy-seven patients converted from gonadotropin/IUI to IVF, 77 consecutive age and attempt number-matched controls (sequential controls [SCs]), and 77 consecutive age-, attempt-, and E(2)-matched controls (E(2) controls [ECs]). INTERVENTION(S): Gonadotropin/IUI cycles with exuberant responses were converted to IVF (cases) to avoid cycle cancellation and high-order multiple pregnancies. MAIN OUTCOME MEASURE(S): Pregnancy rates, delivery rates, E(2) levels, follicle and oocyte number, and fertilization and implantation rates. RESULT(S): Compared with SCs and ECs, cases had more follicles (16.3 +/- 0.6 vs. 13.3 +/- 0.9 and 14.4 +/- 0.9) and higher E(2) at hCG administration (1,951 +/- 93 vs. 1,568 +/- 96 and 1,939 +/- 89 pg/mL). Delivery rates among the three groups (45.5% vs. 32.5% and 39.0%) did not differ significantly. Despite the transfer of fewer embryos in cases than in controls (2.5 +/- 0.1 vs. 3.1 +/- 0.1 and 2.9 +/- 0.1), three triplet pregnancies occurred in cases and three in controls. CONCLUSION(S): Conversion of high responder gonadotropin/IUI patients to IVF is an effective alternative to cycle cancellation and offers a delivery rate as high or higher per cycle than that of planned IVF. Sample size limited the statistical power of the study.     

Cyst aspiration or GnRH antagonist administration for ovarian cysts detected at the start of fresh in vitro fertilization cycles*

The primary objective of this study is to investigate the effect of transvaginal ultrasonogram (TVUS)-guided cyst aspiration or gonadotropin releasing hormone antagonist (GnRH-ant) administration for the management of solitary ovarian cysts detected at the start of in vitro fertilization (IVF) cycles on the outcomes of the same cycles. This is a single-center, retrospective, cohort study of patients who had TVUS-guided cyst aspiration or GnRH-ant treatment for ovarian cysts detected at the start of IVF during a 5-year period. Four hundred and three patients met inclusion criteria: 41 (10.2%) underwent cyst aspiration and 362 (89.2%) were treated with GnRH-ant. There was no difference in the demographics or baseline IVF cycle characteristics of the two groups. Patients treated with GnRH-ant had a longer duration of ovarian stimulation (10.8?±?3.45 days versus 9.05?±?4.06 days, p?=?0.003) and required higher gonadotropin doses (3887.7?±?1097.8?IU versus 3293.7?±?990.5?IU; p?=?0.01) compared with the cyst aspiration group. There was no difference in the clinical pregnancy (43.9% versus 41.4%), spontaneous miscarriage (9.76% versus 8.01%) and live birth (34.1% versus 33.4%) rates between the groups. Our findings suggest that cyst aspiration is comparable to GnRH-ant administration for the management of solitary ovarian cysts detected at the start of IVF cycles.     

体外受精超促排卵治疗中单用促性腺激素和拮抗剂方案临床结局的比较

目的探讨体外受精(IVF)治疗中单用促性腺激素(Gn)对妊娠结局的影响。方法月经第3日开始给予重组卵泡刺激素(rFSH)促排卵,促排卵第6日开始监测血激素水平和阴道超声监测卵泡大小。将达到思则凯添加标准者[黄体生成素(LH)5 IU/L,或LH/基础LH≥3]设为对照组,每日给予思则凯0.125 mg直至人绒毛膜促性腺激素(hCG)注射日;以未达到标准不使用思则凯者设为研究组。结果研究组(n=31)和对照组(n=49)患者在Gn剂量、促排卵天数、hCG注射日血清内分泌水平、获卵数、受精率、着床率、临床妊娠率和活产率方面均无统计学差异(P0.05)。结论在IVF促排卵治疗中,通过对血清LH的监测,如果LH维持在低水平可以不给予拮抗剂治疗,单纯使用Gn是一种经济有效的促排卵方案。     

Minimal ovarian hyperstimulation for in vitro fertilization using sequential clomiphene citrate and gonadotropin with or without the addition of a gonadotropin-releasing hormone antagonist

OBJECTIVE: To compare the results of a minimal-stimulation protocol with those of a standard protocol used for IVF. DESIGN: Retrospective, controlled study. SETTING: University center. PATIENT(S): Fifty-five patients undergoing IVF using a minimal-stimulation protocol with or without adjuvant therapy with a GnRH antagonist. A control group consisted of age- and diagnosis-matched patients undergoing a standard long GnRH agonist (GnRH-a)-gonadotropin stimulation during the same time period. INTERVENTION(S): Clomiphene citrate and gonadotropins, with or without the GnRH antagonist ganirelix. MAIN OUTCOME MEASURE(S): Oocytes recovered and pregnancy rates. RESULT(S): The number of oocytes retrieved was significantly lower for the minimal-stimulation regimen compared with the case of the long GnRH-a protocol (4.8 +/- 2.6 vs. 16.2 +/- 7.5, respectively). The clinical pregnancy rate per transfer, however, was not significantly different between the two regimens (37% vs. 41%, minimal stimulation vs. long GnRH-a protocol, respectively). The addition of ganirelix resulted in at least the same pregnancy outcome as compared with the case of cycles without the antagonist. CONCLUSION(S): Minimal stimulation using clomiphene citrate followed by gonadotropin for IVF results in pregnancy rates equal to the standard long GnRH-a-gonadotropin protocol. The addition of ganirelix resulted in at least similar results with the advantage of eliminating the occurrence of a premature endogenous LH surge.     

GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial

Objective

To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders.

Study design

This was a randomized controlled trial performed in the Iakentro IVF centre, Thessaloniki, from January 2007 to December 2011, concerning women characterised as poor responders after having 0–4 oocytes retrieved at a previous IVF cycle. They were assigned at random, using sealed envelopes, to either a long GnRH agonist protocol (group I) or a GnRH antagonist protocol (group II).

Results

Overall 364 women fulfilled the inclusion criteria and were allocated to the two groups: finally 330 participated in our trial. Of these, 162 were treated with the long GnRH agonist protocol (group I), and 168 with the fixed GnRH antagonist protocol (group II). Numbers of embryos transferred and implantation rates were similar between the two groups (P = NS). The overall cancellation rate was higher in the antagonist group compared to the agonist group, but the difference was not significant (22.15% vs. 15.2%, P = NS). Although clinical pregnancy rates per transfer cycle were not different between the two groups (42.3% vs. 33.1%, P = NS), the clinical pregnancy rate per cycle initiated was significantly higher in the agonist compared to the antagonist group (35.8% vs. 25.6%, P = 0.03).

Conclusions

Although long GnRH agonist and fixed GnRH antagonist protocols seem to have comparable pregnancy rates per transfer in poor responders undergoing IVF, the higher cancellation rate observed in the antagonist group suggests the long GnRH agonist protocol as the first choice for ovarian stimulation in these patients.     

Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study

Purpose  Embryological and clinical efficacy of gonadotropin-releasing hormone (GnRH) antagonist and agonist stimulation protocols in non-obese women with polycystic ovarian syndrome (PCOS) were compared. Methods  A prospective randomized study. Setting: Medical University Hospital. Patients: 70 infertile PCOS patients; 33 in GnRH antagonist and 37 in GnRH agonist group. Results  Similar mature metaphase II oocyte rate (76% vs. 76%) was observed in both protocols. Optimal pronuclear morphology zygotes dominated in both groups (64% vs. 66%). Transferred embryo quality did not differ in both protocols. No significant differences between both protocols were found in delivery rate (p = 0.481), pregnancy rate (p = 0.810), multiple pregnancy rate (p = 0.501), miscarriage rate (p = 0.154), fertilization rate (p = 0.388) and implantation rate (p = 1.000). Duration of stimulation and total follicle-stimulating hormone (FSH) dose were significantly lower in GnRH antagonist protocol (p = 0.0005). Conclusions  GnRH antagonist and agonist protocols in non-obese PCOS patients yield similar embryological and clinical outcomes. Shorter duration of treatment and lower FSH requirement in GnRH antagonist group may be financially beneficial and therefore attractive for patients. Capsule GnRH antagonist and agonist protocols in non-obese PCOS patients yield similar embryological and clinical outcomes. GnRH antagonist protocols may be financially and clinically attractive for patients undergoing IVF.     

A comparative study on oxidative and antioxidative markers of serum and follicular fluid in GnRH agonist and antagonist cycles

Objective

To determine whether concentrations of oxidative stress markers of follicular fluid and serum are different in GnRH agonist protocol from GnRH antagonist protocol.

Material and method

This was a cross-sectional study. Eighty-four women undergoing controlled ovarian stimulation with either GnRH agonist (n = 39) or GnRH antagonist protocols (n = 45) for IVF/ICSI treatment were assigned by a physician. Blood was obtained at the time of oocyte retrieval, and follicular fluid (FF) from the mature follicles of each ovary was centrifuged and frozen until analysis. Malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC), hydroxyl proline (OH-P), sodium oxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), adenosine deaminase (ADA) and xanthine oxidase (XO) were assessed in the serum and follicular fluid of each participants.

Results

The mean serum concentrations of GSH-Px, GSH and MDA were lower in the GnRH antagonist group compared to GnRH agonist group, but mean serum SOD was higher in the GnRH antagonist group. The mean follicular SOD, ADA and NO were higher in GnRH antagonist group than GnRH agonist group. The IVF/ICSI outcomes were similar in both groups.

Conclusion(s)

GnRH antagonist protocol is associated with increased oxidative stress. The relation of GnRH analogues with oxidative stress and its implication in follicular growth needs to be addressed in further studies.     

Addition of a gonadotropin releasing hormone (GnRH) antagonist and exogenous gonadotropins to unstimulated in vitro fertilization (IVF) cycles: Physiologic observations and preliminary experience

Purpose To describe our preliminary experience with the addition of a GnRH antagonist (Nal-Glu) and exogenous gonadotropins (follicle stimulating hormone; FSH) to unstimulated IVF cycles.Method Seven spontaneously ovulatory women underwent eight unstimulated IVF cycles at our institution. They were treated with a single dose of Nal-Glu, 50 g/ kg, or with a combination of Nal-Glu, 50 g/kg, and exogenous FSH, 150–300 IU, during the late follicular phase of spontaneous cycles. They then received 10,000 IU of human chorionic gonadotropin (hCG) to time accurately follicle aspiration in unstimulated IVF cycles.Results Two women underwent three cycles with Nal-Glu alone on the day of hCG administration. One pregnancy resulted. Five women underwent five cycles with 3 to 6 days of daily Nal-Glu and FSH. Four of these cycles resulted in aspiration after the FSH dose was increased to 300 IU. Nal-Glu and FSH allowed continued development of the dominant follicle without the occurrence of luteinizing hormone (LH) surge.Conclusions (1) Nal-Glu alone given 18 hr prior to hCG did not interfere with continued follicle viability or with the attainment of pregnancy. (2) Simultaneous Nal-Glu and FSH allowed for continued growth and development of the dominant follicle without the occurrence of an LH surge. (3) This preliminary experience confirms the feasibility of this novel approach, which may ultimately enhance the efficacy of unstimulated IVF cycles by eliminating premature ovulation and maximizing control of gonadotropin delivery to the developing follicle.Presented at the 39th Meeting of The Society for Gynecologic Investigation, San Antonio, Texas, March 18–21, 1992.     

Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer

Background.?The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and randomised to receive GnRH-antagonist or the GnRH-agonist. The endpoints were the pattern of follicular growth, the maturity of the oocytes collected, the embryo quality and the pregnancy outcome.

Methods.?A total of 136 patients undergoing IVF were included. Sixty-seven patients were allocated to the GnRH antagonist and 69 patients to the GnRH agonist. GnRH antagonist was administered when the leading follicle reached a diameter of 12–14 mm. GnRH agonist was administered in a long luteal protocol.

Results.?The mean numbers of oocytes retrieved and mature oocytes were significantly higher in the agonist than in the antagonist group (p < 0.02 and p < 0.01, respectively). Embryo quality, implantation rate, clinical pregnancy rates, ongoing pregnancy rate and miscarriage rate were similar in both groups.

Conclusions.?Better follicular growth and oocyte maturation are achieved with GnRH agonist treatment. However, both regimens seem to have similar efficacy in terms of implantation and pregnancy rates. Further studies clarifying the effect of the GnRH antagonist on ovarian function are needed, as well as a clear definition of the best period of the follicular phase for the GnRH antagonist administration.     

Ovarian stimulation in women with high and normal body mass index: GnRH agonist versus GnRH antagonist

In modern society, obesity has become a major health problem and has been associated with impaired fertility. The aim of this study is to assess the role of obesity in women undergoing controlled ovarian hyperstimulation (COH) stimulated either with GnRH agonists or with GnRH antagonists. Records of 463 women undergoing in vitro fertilization (IVF) treatment were reviewed. The influence of body mass index (BMI) on treatment outcome was examined, after accounting for differences in stimulation protocols. In the agonist group (286 patients), the total amount of gonadotropins used was significantly higher in patients with a BMI ≥ 25?kg/m², when compared to those with a normal BMI. The same result was found in the antagonist group (177 patients). No significant differences were found in length of stimulation, number of oocytes retrieved or number of embryos transferred. In both the antagonist and the agonist group, the number of clinical pregnancies was found to be higher in patients with normal BMI, suggesting that obesity could impair the ovarian response to exogenous gonadotropins. Considering the results obtained and the many theoretical advantages of GnRH antagonists, ovarian stimulation with GnRH antagonists is an efficient treatment for both women with normal and high BMI.