Time to revolutionize ovarian stimulation

Edwards, Robert G.; Løbo, Rogerio A.; Bouchard, P.

doi:10.1093/oxfordjournals.humrep.a019317

Cited by 142 publications

(48 citation statements)

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“…For example, in sheep and humans, ovulation rates after super ovulation treatments continue to be highly variable (Table 1). 1,2 Moreover, when mature oocytes are subjected to IVF and multiple blastocysts result, the selection of the best of these for transfer remains an educated guess. Therefore, in terms of positive pregnancy outcomes, success rates following IVF or embryo recovery and transfer to recipients are often low (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

McNatty¹,

Juengel²,

Pitman³

2014

Reproductive Biology Insights

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ABSTRACT:The use of exogenous gonadotropins to increase oocyte yields for better pregnancy outcomes remains unpredictable and inefficient. The objectives of this review are to address two questions concerning this issue: (1) are there any alternatives for improving consistency in oocyte yields? (2) is it possible to develop a molecular diagnostic test for oocytes with blastocyst potential? Studies in sheep with a heterozygous inactivating mutation in the oocyte-derived growth factor, bone morphogenetic protein 15 (BMP15), report increased oocyte yields and significantly more offspring. Moreover, partial immuno-neutralization of BMP15 bioactivity increases oocyte yield without modifying gonadotropin or ovarian steroid secretion. Therefore, it is hypothesized that the development of BMP15 antagonists may prove them to be suitable alternatives to exogenous gonadotropins. Recent evidence from analyses of candidate gene expression in human cumulus cells separated from individual oocytes before IVF indicates a potential non-invasive molecular screen for oocytes with improved blastocyst and live-birth outcomes.

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Section: Introductionmentioning

confidence: 99%

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

McNatty¹,

Juengel²,

Pitman³

2014

Reproductive Biology Insights

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“…Problems related to ovarian stimulation include emotional stress, abdominal discomfort, short-term complications such as ovarian hyperstimulation syndrome and multiple gestation, and uncertainties regarding long-term health consequences (2). Many of the problems associated with current IVF stimulation regimens relate to the unphysiological approach to ovarian (hyper)stimulation (3). Preceding the administration of high doses of gonadotropins, pituitary down-regulation is normally achieved by prolonged administration of GnRH agonists (the so-called long protocol).…”

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confidence: 99%

A Randomized Comparison of Two Ovarian Stimulation Protocols with Gonadotropin-Releasing Hormone (GnRH) Antagonist Cotreatment forin VitroFertilization Commencing Recombinant Follicle-Stimulating Hormone on Cycle Day 2 or 5 with the Standard Long GnRH Agonist Protocol

Hohmann

Macklon

Fauser

2003

The Journal of Clinical Endocrinology & Metabolism

246

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Extending the FSH window for multifollicular development by administering FSH from the midfollicular phase onward constitutes a novel mild protocol for ovarian stimulation for in vitro fertilization (IVF) based on the physiology of single dominant follicle selection in normo-ovulatory women. We compared outcomes from this protocol with two other stimulation protocols. One hundred and forty-two normo-ovulatory patients with an indication for IVF (or IVF/ICSI) were randomized to a GnRH agonist long protocol (group A; n ‫؍‬ 45) or one of two GnRH antagonist protocols commencing recombinant FSH on cycle d 2 (group B; n ‫؍‬ 48) or cycle d 5 (group C; n ‫؍‬ 49). A fixed dose (150 IU/d) of rFSH was used for ovarian stimulation, and GnRH antagonist cotreatment was initiated on the day when the leading follicle reached 14 mm diameter.Group C showed a shorter duration of stimulation (median duration, 11, 9, and 8 d for groups A, B, and C, respectively; P < 0.001), reflected in a significantly lower total dose of rFSH used (median amount of rFSH, 1650, 1350, and 1200 IU for groups A, B, and C, respectively; P < 0.001). In group C more cycles were cancelled during the stimulation phase due to insufficient response, resulting in a lower percentage of oocyte retrievals (84%, 73%, and 63% for groups A, B, and C; P ‫؍‬ 0.02). However, women in group C obtained better quality embryos (percentage of embryo score of 1 for best embryo, 29%, 37%, and 61% for groups A, B, and C, respectively; P ‫؍‬ 0.008), resulting in more transfers per oocyte retrieval (68%, 71%, and 90% for groups A, B, and C, respectively; P ‫؍‬ 0.04). After profound ovarian stimulation (groups A and B) only 7% of the patients who retrieved four oocytes or less conceived, whereas after mild stimulation (group C) 67% of these patients conceived (P < 0.01). Overall, no differences were found among the three groups comparing pregnancy rate per started IVF cycle.In conclusion, application of the described mild ovarian stimulation protocol resulted in pregnancy rates per started IVF cycle similar to those observed after profound stimulation with GnRH agonist cotreatment despite shorter stimulation and a 27% reduction in exogenous FSH. A higher cancellation rate before oocyte retrieval was compensated by improved embryo quality concomitant with a higher chance of undergoing embryo transfer. A relatively low number of oocytes retrieved after mild ovarian stimulation distinctly differs from the pathological reduction in the number of oocytes retrieved after profound ovarian stimulation (poor response) associated with poor IVF outcome. The relatively small number of oocytes obtained after mild ovarian stimulation may represent the best of the cohort in a given cycle. (J Clin Endocrinol Metab 88: 166 -173, 2003) C ONVENTIONAL OVARIAN STIMULATION protocols aim to stimulate the growth of many follicles to obtain multiple oocytes for in vitro fertilization (IVF) and thus multiple embryos, allowing selection for transfer (1). Currently applied standard IVF protocols take many ...

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“…Elective single embryo transfer with subsequent cryopreservation of other viable embryos could further increase the benefits from the mild strategy. Moreover, mild approaches may reduce patient dropout and thereby improve cumulative birth rates as predicted by Edwards et al [30].…”

Section: Discussionmentioning

confidence: 92%

Mild IVF using GnRH agonist long protocol is possible: Comparing stimulations with 100 IU vs. 150 IU recombinant FSH as starting dose

Fernández-Shaw¹,

Esturo²,

R³

et al. 2009

J Assist Reprod Genet

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Purpose To test the possibility of stimulating ovaries with a mild IVF approach using a GnRH agonist long protocol. Methods Retrospective study of 142 first IVF cycles of women aged 30 to 35 who had undergone stimulation with 100 IU or 150 IU of rFSH. Results The mean dose of rFSH used was smaller in the low dose compared with the high dose group (999 vs. 1343 IU; p<0.001), obtaining comparable numbers of mature oocytes in both groups. Additionally, reducing the mean number of embryos transferred from 1.8 to 1.5 significantly decreased the twin rate in the low dose group while maintaining similar pregnancy rates in both groups. Conclusions It is possible to develop mild IVF using GnRH agonist long protocol in women with good prognosis. A reduced amount of rFSH and fewer transferred embryos allow for lower costs and risks of IVF without compromising the pregnancy rate.

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Time to revolutionize ovarian stimulation

Cited by 142 publications

References 0 publications

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

A Randomized Comparison of Two Ovarian Stimulation Protocols with Gonadotropin-Releasing Hormone (GnRH) Antagonist Cotreatment forin VitroFertilization Commencing Recombinant Follicle-Stimulating Hormone on Cycle Day 2 or 5 with the Standard Long GnRH Agonist Protocol

Mild IVF using GnRH agonist long protocol is possible: Comparing stimulations with 100 IU vs. 150 IU recombinant FSH as starting dose

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