Less is more: increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth after in vitro fertilization

Pal, Lubna; Jindal, Sangita; Witt, Barry R.; Santoro, Nanette

doi:10.1016/j.fertnstert.2007.05.055

Cited by 81 publications

(63 citation statements)

References 25 publications

(36 reference statements)

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“…These observations agree with previous reports, that showed that a high Gn dose is effective in getting more oocytes [8,24] and avoiding cycle cancellation [8], but does not improve IVF results [6][7][8]24]. This could be due to a negative impact of high Gn dose on endometrial quality [25] or, alternatively, to the fact that a high dose of exogenous Gn could force the recruitment of "resistant" follicles, hosting oocytes of poor quality from which poor competence embryos derive [26].…”

Section: Discussionsupporting

confidence: 91%

“…In the last years, the most frequently used COH regimen for expected poor responders has been the "long" protocol with a high daily Gn dose (300-450 IU/d) [4]. Unfortunately, however, despite the higher number of retrieved oocytes this regimen failed to improve the final IVF success rate, implying, on the other side, a relevant increase of economical costs of IVF procedure [6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…Giving a high Gn dose obviously increases the cost of IVF, a consequence that would be acceptable if paralleled by an improvement in IVF outcome. Unfortunately, however, the available data suggest that increasing the daily Gn dose may increase the number of retrieved oocytes, but not the final success rate of IVF [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

“Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial

Revelli

Chiadò

Dalmasso³

et al. 2014

J Assist Reprod Genet

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Background This large prospective, randomized study was designed to compare the "mild" protocol with clomiphene citrate, low-dose gonadotropins and a GnRH-antagonist (CC/Gn/GnRH-ant protocol) with the "long" protocol with a GnRH-agonist and high-dose Gn for the controlled ovarian hyperstimulation (COH) of patients with expected poor ovarian responsiveness undergoing IVF. Materials and Methods A total of 695 women with clinical, endocrine and ultrasound characteristics suggesting a low ovarian reserve and a poor responsiveness to COH were recruited and randomly assigned to receive the CC/Gn/ GnRH-ant "mild" protocol (mild group, n=355) or the "long" protocol with high-dose Gn (long group, n=340). Results The "mild" stimulation led to significantly shorter follicular phase, lower consumption of exogenous Gn and lower peak estradiol level than the "long" regimen. With the "long" protocol, significantly less cycles were cancelled due to the lack of ovarian response; further, it obtained significantly more oocytes, more mature oocytes, more embryos, and a thicker endometrium. As for the final IVF outcome, however, the two stimulation regimens obtained comparable implantation rate, clinical pregnancy rate, and ongoing pregnancy rate at 12 weeks. Conclusions In conclusion, the "mild" CC/Gn/GnRH-ant stimulation protocol is a valid alternative to the long protocol with high Gn dose as it obtains a comparable success rate and requires significantly less medications, with an obvious economical advantage.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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“Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial

Revelli

Chiadò

Dalmasso³

et al. 2014

J Assist Reprod Genet

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“…To overcome these deficiencies, besides reducing the impact of ovarian stimulation [41], one of the main goals of human assisted reproduction-related research is the improvement of culture conditions. This has led on one side to the use of chemically defined media containing growth factors [33], on the other side to the development of culture systems employing co-culturing with growth factor-releasing cells [47], so that dramatic improvements in the composition of embryo culture media have been made in the last 15 years allowing the efficient production of viable human blastocysts.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, it reduces the amount of FSH and days needed for proper stimulation, parameters directly linked to the chance of pregnancy [41].…”

Section: Introductionmentioning

confidence: 99%

Improvement of mouse embryo quality by myo-inositol supplementation of IVF media

Colazingari

Fiorenza

Carlomagno³

et al. 2014

J Assist Reprod Genet

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Objective Myo-inositol (myoIns) has a positive role in mammalian development and human reproduction. Since experiments on farming species suggest a similar role in preimplantation development, we evaluated the hypothesis that the inclusion of myoIns in human embryo culture media would produce an increase in embryo quality in IVF cycles, using the mouse embryo assay. Methods To determine the effect of myoIns on completion of preimplantation development in vitro, one-cell embryos of the inbred C57BL/6N mouse strain were produced by ICSI, cultured in human fertilization media in the presence of myoIns (myoIns+) or in its absence (myoIns-) and evaluated morphologically. Daily progression through cleavage stages, blastocyst production and expansion and blastomere number at 96 hours post fertilization were assessed. Results Compared to myoIns-embryos, myoIns+ embryos displayed a faster cleavage rate and by the end of preimplantation development, the majority of myoIns+ blastocysts was expanded and formed by a higher number of blastomeres. Conclusion The presence of myoIns resulted in both an increase in proliferation activity and developmental rate of in vitro cultured early mouse embryos, representing a substantial improvement of culture conditions. These data may identify myoIns as an important supplement for human embryo preimplantation culture.

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Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer

Ni,

Zhou,

Liu

et al. 2024

JAMA Netw Open

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ImportanceThe safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive.ObjectiveTo evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility.Design, Setting, and ParticipantsThis study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and &lt;10 days), group 2 (≤1500 IU and ≥10 days), group 3 (&gt;1500 IU and &lt;10 days), and group 4 (&gt;1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023.InterventionsBlastocyst biopsy and PGT-A.Main outcomes and measuresThe primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer.ResultsA total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]).Conclusions and relevanceIn this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate.Trial RegistrationClinicalTrials.gov Identifier: NCT03118141

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Less is more: increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth after in vitro fertilization

Cited by 81 publications

References 25 publications

“Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial

“Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial

Improvement of mouse embryo quality by myo-inositol supplementation of IVF media

Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer

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