Conventional GnRH antagonist protocols versus long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovary syndrome women: a systematic review and meta-analysis

Kadoura, Sally; Alhalabi, Marwan; Nattouf, Abdul Hakim

doi:10.1038/s41598-022-08400-z

Cited by 36 publications

(30 citation statements)

References 82 publications

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“…The conventional long protocol of ovarian stimulation for IVF-embryo transfer is based upon the administration of exogenous Gn combined with GnRHa. The aim of using GnRHa is to prevent the premature rise of LH due to positive feedback by the high serum concentration of estradiol[ 13 - 15 ]. The use of GnRHa is associated with an increased incidence of functional ovarian cysts; this may be the effect of the “flare-up” phenomenon of GnRHa.…”

Section: Discussionmentioning

confidence: 99%

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins: Two case reports

Li¹,

Su²,

Zhou³

2023

World J Clin Cases

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BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5% to 16.7% in developed countries and 6.9% to 9.3% in developing countries. This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability. The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million. Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments. The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology. Conventional ovarian stimulation protocols for in vitro fertilization (IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone (GnRH) analogues, either GnRH agonists (GnRHa) or antagonists. The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation. However, in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone. CASE SUMMARY Here, two case studies were conducted. In the first case, a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center. Fourteen days after triptorelin acetate was administrated (day 18 of her menstrual cycle), bilateral ovaries presented polycystic manifestations. The patient was given 5000 IU of human chorionic gonadotropin. Twenty-two oocytes were obtained, and eight embryos formed. Two blastospheres were transferred in the frozen-thawed embryo transfer cycle, and the patient was impregnated. In the second case, a 37-year-old woman presented to the reproductive center for her first donor IVF cycle. Fourteen days after GnRHa administration, the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries. The patient was given 10000 IU of human chorionic gonadotropin. Three oocytes were obtained, and three embryos formed. Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle, and the patient was impregnated. CONCLUSION These two special cases provide valuable knowledge through our experience. We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions. Considering the high progesterone level in most cases of this situation, we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.

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Section: Discussionmentioning

confidence: 99%

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins: Two case reports

Li¹,

Su²,

Zhou³

2023

World J Clin Cases

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“…Inhibition gonadotropin reduces AMH expression from granulosa cells of early-preantral follicles of the marmoset ovary [63] while treating human granulosa cells obtained from the follicular uid samples of IVF/ICSI cycles with FSH represses AMH expression which explain the negative correlation between the FF AMH and the total FSH dose that was observed in the current study. However, the lower gonadotropin requirements [65] during the GnRH antagonist protocol might hinder the correlation from reaching signi cance levels in the PCOS-Anta group. Similarly, we noted signi cantly negative correlations between the FF AMH levels and the number of retrieved oocytes, MII oocytes, MI oocytes, GV oocytes, immature oocytes, fertilized oocytes, and the number of obtained embryos in the PCOS-A group only.…”

Section: Discussionmentioning

confidence: 99%

Correlations between follicular fluid AMH and IVF/ICSI outcomes among polycystic ovary syndrome women using different controlled hyperstimulation protocols

Kadoura

Alhalabi

Nattouf

2022

Preprint

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Background Anti-Müllerian hormone (AMH) is a glycoprotein that plays an important role in the regulation of ovarian folliculogenesis. However, the data link between its follicular fluid levels (FF AMH) and the IVF/ICSI outcomes in polycystic ovary syndrome (PCOS) women are limited, contradicted, and mainly obtained from Long-GnRH agonist cycles. Thus, we conducted this study to compare the correlations between the FF AMH levels and the IVF/ICSI outcomes in PCOS women during different controlled hyperstimulation protocols. Methods The current study is a re-analysis of our previous work. The data were adopted from a prospective trial that was conducted on women who were referred to the Assisted Reproductive Unit of Orient Hospital, Damascus, Syrian Arab Republic, from December 2019 to August 2021. A total of 75 PCOS women (Rotterdam criteria) (GnRH agonist group, PCOS-A, n = 53; GnRH antagonist group, PCOS-Anta, n = 22) were included. Follicular fluid samples were collected on the retrieval day, and the FF AMH levels were measured using ELISA Kits. In addition, the embryological and clinical IVF/ICSI outcomes were detected. Spearman rank correlation coefficients were computed to assess the correlations among the studied parameters. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of FF AMH levels in predicting pregnancy rates. Results The patients’ baseline characteristics were comparable between the PCOSA and the PCOSAnta groups. FF AMH levels were negatively correlated with the total FSH dose, the number of retrieved, MII, MI, germinal vesicle, immature, and fertilized oocytes, and with the number of obtained embryos in the PCOSA group, but not in the PCOSAnta one. Nevertheless, there were not any correlations between FF AMH levels and the rates of oocyte maturation or fertilization, or with the highquality embryo rate, embryos cleavage rate or implantation rate in any of the studied groups. In addition, no significant differences were noted in FF AMH levels between pregnant and non-pregnant women in any of the studied groups, which also was confirmed by the Receiver Operating Characteristic (ROC) Curve analysis. Discussion Since the FF AMH levels do not correlate with the maturation rate, fertilization rate, or embryos cleavage rate, the negative correlations in the PCOSA group arise from the negative impacts of the FF AMH on the number of retrieved oocytes. During the long agonist protocol, since PCOS follicles have good follicular angiogenesis, the number of retrieved oocytes would mostly depend on the negative effects of the FF AMH on folliculogenesis. However, during the GnRH antagonist protocol, the limited angiogenesis acts together with the high levels of FF AMH to reduce the number of retrieved oocytes. Conclusions High FF AMH negatively affects ovarian folliculogenesis during both; the long GnRH agonist protocol and the flexible GnRH antagonist one. However, the different patterns of follicular angiogenesis during the two protocols would affect the dependency of the oocytes' yield on the follicular fluid levels of AMH. Study registration: The data were adopted from a prospective clinical trial that was registered on the clinicaltrials.gov site by registration numbers NCT04727671.

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“…A recent meta-analysis including 10 studies and 1214 women comparing GnRH agonist to antagonist protocols in PCOS patients confirmed the findings of similar pregnancy outcomes for agonist and antagonist protocols. They also found that antagonist protocols had a significantly lower rate of OHSS, lower gonadotropin consumption, and shorter duration of stimulation [16]. All patients in the included studies had been on combined oral contraceptive (COC) for at least 21 days prior to stimulation start.…”

Section: Key Pointsmentioning

confidence: 98%

Optimization of assisted reproductive technology outcomes in patients with polycystic ovarian syndrome: updates and unanswered questions

Fitz

Mahalingaiah

2022

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of reviewNarrative review of recent literature on optimization of assisted reproduction technology outcomes in patients with polycystic ovarian syndrome (PCOS). Recent findingsThe key areas of focus include pre cycle treatment with the goal of cohort synchronization, methods of ovulation suppression and trigger medication. There is no definitive evidence that precycle treatment with combined oral contraceptives (COCs) or progestins improve or negatively impact in vitro fertilization outcomes in patients with PCOS. The reviewed evidence supports consideration of progestins as suppression of premature ovulation in patients with PCOS as an alternative to gonadotropin releasing hormone (GnRH) antagonist if a freeze all protocol is planned. There is limited prospective evidence in PCOS populations regarding use of a dual trigger using GnRH agonist and human chorionic gonadotropin (hCG).

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Conventional GnRH antagonist protocols versus long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovary syndrome women: a systematic review and meta-analysis

Cited by 36 publications

References 82 publications

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins: Two case reports

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins: Two case reports

Correlations between follicular fluid AMH and IVF/ICSI outcomes among polycystic ovary syndrome women using different controlled hyperstimulation protocols

Optimization of assisted reproductive technology outcomes in patients with polycystic ovarian syndrome: updates and unanswered questions

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