Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens

Fanchin, Rénato; Cunha-Filho, João Sabino; Schönauer, Luca Maria; Kadoch, Isaac Jacques; Cohen-Bacri, Paul; Frydman, René

doi:10.1016/s0015-0282(02)04574-0

Cited by 72 publications

(69 citation statements)

References 19 publications

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“…Larger follicles are more sensitive to FSH and, therefore, begin to respond and develop during the late luteal phase [7,9,13,14]. Thus, asynchronous follicular growth during controlled ovarian hyper stimulation may be an outcome of the size heterogeneities of early antral follicles during the early follicular phase [7].…”

Section: Discussionmentioning

confidence: 99%

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A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients

Davar

Rahsepar

Rahmani

2012

Arch Gynecol Obstet

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Purpose This study aims to verify if luteal estradiol pretreatment improves IVF/ICSI outcomes in a GnRH antagonist protocol as compared with a micro dose GnRH agonist protocol in poor-responding patients. Methods A total of 116 IVF/ICSI cycles were included in this prospective randomized single blind clinical trial. The selected women were randomly assigned to receive an estradiol pre-treatment in a GnRH antagonist protocol (daily oral Estradiol Valerate 4 mg preceding the IVF cycle from the 21st day until the first day of the next cycle) or in oral contraceptive pill micro dose GnRH agonist protocol. Results The patients in the luteal estradiol protocol required more days of stimulation (10.9 ± 1.6 vs. 10.2 ± 1.8) and a greater gonadotropin requirement (3,247.8 ± 634.6 vs. 2,994.8 ± 611 IU), yet similar numbers of oocytes were retrieved and fertilized. There was no significant difference between the two groups in terms of the implantation rates (9.8 vs. 7.9 %) and the clinical pregnancy rates per transfer (16.3 vs. 15.6 %). Conclusion This study demonstrates that the use of estradiol during a preceding luteal phase in a GnRH antagonist protocol can provide similar IVF outcomes when compared to a micro dose GnRH agonist protocol.

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Section: Discussionmentioning

confidence: 99%

“…[6]. An approach for treating poor responders is to give E2 in the luteal phase before IVF hyper stimulation [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients

Davar

Rahsepar

Rahmani

2012

Arch Gynecol Obstet

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“…The concept of a luteal E2 protocol was first suggested by Fanchin et al based on the assumption that reducing the size, and improving the homogeneity, of early antral follicles would optimize the ovarian response and improve cycle outcomes [18,19]. Follicular discrepancy, which results from a dissimilar sensitivity of each follicle to FSH and the gradual elevation of FSH after the demise of the corpus luteum, has been shown to be counter-reproductive, and adjuvant GnRH agonists and oral contraceptive (OC) pills are commonly used to offset this discrepancy [2].…”

Section: Discussionmentioning

confidence: 99%

“…Both actions can be executed and maintained even at the low physiological ranges of serum E2 levels [17]. Previous studies have shown that utilizing the natural negative feedback of the hypothalamus-pituitary-ovary axis induced by E2 pretreatment can effectively prevent inter-cycle increases in follicle-stimulating hormone (FSH), improve follicle synchronization, and eventually result in more coordinated follicular development, leading to the recovery of more mature oocytes [18,19]. However, these studies were not designed to detect improvements in pregnancy outcomes, and there was important methodological bias in that patients were using their own preceding failed cycle as a control.…”

Section: Introductionmentioning

confidence: 99%

Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization

Chang

Han

Won

et al. 2011

J Assist Reprod Genet

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Purpose To verify whether a novel protocol administering E 2 during the luteal phase of the preceding cycle and during ovarian stimulation in GnRH antagonist cycle could enhance follicular response and hence improve outcomes in poor responders. Methods In this retrospective analysis, a total of 155 poor responder patients subjected to IVF/ICSI were analyzed. All the patients had history of more than one prior IVF cycle failure with poor response (less than 5 oocytes retrieved and/ or maximal E 2 level less than 500 pg/mL) by using conventional long agonist or antagonist protocol. In luteal E2 treatment protocol (n086), oral estradiol valerate 4 mg/day was initiated on luteal day 21 and either stopped at menstrual cycle day 3 (Protocol A, n028) or continued during the period of ovarian stimulation until the day of hCG injection (Protocol B, n058). IVF parameters and pregnancy outcome of luteal E2 treatments group were compared with a standard GnRH antagonist protocol (n069) which the patients received no hormonal pretreatment. Results Compared to standard GnRH antagonist protocol, cancellation rate was lower with luteal E2 group (15.1% vs 37.7%, p<0.01). Moreover, patients treated with luteal estrogen resulted in an increased number of oocytes retrieved (4.5±2.9 vs 3.2±1.9; p<0.01). A trend toward increase in number of normally fertilized embryos (2.9±2.1vs 2.3±1.9; p00.043), and increased prevalence of good quality embryos (51.2% vs 25%; p00.047) were noted. Comparing protocol A and B, there were no significant difference between embryologic data, however there were slight increase in ongoing pregnancy rate in protocol B compared to A (27.1% vs 20%, p00.357), although statistical significance was not achieved. Conclusion Estrogen priming through luteal phase and stimulation phase improved ovarian responsiveness and this may lead to an increase in pregnancy rate in poor responders with failed cycle.

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“…And then we assumed that the less competent oocyte is caused by asynchronous follicular development and a limited number of dominant follicles due to ovarian stimulation without pituitary suppression in GnRH antagonist protocols. Asynchronous multi-follicular growth during COH may be a direct consequence of size heterogeneities of early antral follicles dur- ing the early follicular phase [12]. Luteal estradiol administration strengthens the relationship between day 3 FSH and inhibin B levels and ovarian follicular status [13].…”

Section: Discussionmentioning

confidence: 99%

Oral contraceptive pill pretreatment in ovarian stimulation with GnRH antagonists for in vitro fertilization: A comparative study

Choo

Han

Yang

et al. 2011

Korean J Obstet Gynecol

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ObjectiveTo evaluate whether oral contraceptive pill (OCP) pretreatments in gonadotropin-releasing hormone (GnRH) antagonist ovarian stimulation protocols takes positive effects on in vitro fertilization (IVF) outcomes in respect to retrieved oocyte number, oocyte maturation rate, fertilization rate, good quality embryo rate, cycle cancellation rate, pregnancy rate and clinical abortion rate. MethodsA total of 194 cycles using GnRH antagonist protocol was performed at infertility clinic of our institute from September 1st, 2009 to February 28th, 2010. The medical records of GnRH antagonist protocols for IVF with or without OCP pretreatment in our IVF unit were retrospectively analyzed. We compared the IVF outcomes between OCP pretreated (n=41) and no pretreatment group (n=153). ResultsIn cycles with OCP pretreated group, the total used dosage of gonadotropin (3019.38±1379.00 IU) were higher than that of no pretreatment group (2551.52 ± 1157.05 IU, P = 0.054). The duration of ovarian stimulation in OCP pretreated group (11.5 ± 2.0) was signifi cantly longer than that of control group (9.5 ± 1.9, P = 0.000). The number of gained total embryo (2.8±0.9 vs. 2.5±1.0, P = 0.055) and fertilization rate (77.2% vs. 65.5%, P = 0.017) were significantly higher in OCP pretreated group. There is no signifi cant difference in pregnancy rate between two groups (39.4% vs. 30.0%, P = 0.304). ConclusionOCP pretreatment before GnRH antagonist protocol for IVF appears not to have reliable benefi t in terms of IVF outcomes. Wellcontrolled and large-scaled studies are needed.

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Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens

Cited by 72 publications

References 19 publications

A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients

A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients

Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization

Oral contraceptive pill pretreatment in ovarian stimulation with GnRH antagonists for in vitro fertilization: A comparative study

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