The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response

Sekhon, L.; Shaia, Kathryn L.; Santistevan, Anthony; Cohn, K. Hunter; Lee, Joseph A.; Beim, P. Yurttas; Copperman, A.B.

doi:10.1007/s10815-017-0909-3

Cited by 59 publications

(37 citation statements)

References 36 publications

(40 reference statements)

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“…In our study, deeper pituitary suppression was observed in the EFLL protocol, and the level of LH on hCG administration day was significantly lower than that in the MLSL protocol for PGT. Although the duration and dosage of Gn were elevated when pituitary function was strongly suppressed ( 30 ), several studies have found no association between Gn dosage and embryo euploidy ( 31 – 33 ). We speculate that the lower LH levels found with the EFLL protocol and the decreased possibility of premature LH surge reduced the likelihood of abnormal meiotic division of oocytes, leading to a higher euploidy rate.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Number of Euploid Embryos in Preimplantation Genetic Testing Cycles With Early-Follicular Phase Long-Acting Gonadotropin-Releasing Hormone Agonist Long Protocol

Niu

et al. 2020

Front. Endocrinol.

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Studies have shown that early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol (EFLL), a popular controlled ovarian hyperstimulation protocol widely used in China, leads to higher rates of implantation and clinical pregnancy, as well as lower rates of spontaneous abortion and ectopic pregnancy in patients undergoing in vitro fertilization treatment. However, the impact of EFLL on euploid embryos and its underlying mechanisms remain unclear. To address these gaps of knowledge, we conducted a retrospective comparative study of 310 preimplantation genetic testing (PGT) cycles with a total of 1,541 embryos using the EFLL protocol or midluteal short-acting GnRH agonist long protocol (MLSL). Patients were matched by PGT subtype [aneuploidies (PGT-A) vs. PGT for chromosomal structural rearrangements (PGT-SR)], age (±2 years), and body mass index (±1 kg/m 2 ). For PGT-A, there was no significant difference in the number of euploid embryos (1.80 ± 1.47 for EFLL vs. 1.84 ± 2.03 for MLSL, p > 0.05) or the rate of euploidy (44.6 vs. 36.9%, p > 0.05). For PGT-SR, the number of euploid embryos in the EFLL group was significantly higher than that in the MLSL group (1.76 ± 1.54 vs. 1.21 ± 1.24, p < 0.05). A higher euploidy rate was also observed with the EFLL protocol compared with that obtained in MLSL (31.9 vs. 25.7%), although the difference was not statistically significant ( p > 0.05). Compared with the MLSL protocol, more euploid embryos were achieved when using the EFLL protocol in PGT-SR, demonstrating the value in PGT-SR. To the best of our knowledge, this study is the first one to compare embryonic outcomes between EFLL and MLSL, providing key insights into the clinical application of EFLL in PGT cycles. In the light of the limited sample size of our study, we recommend that these questions be explored using a larger prospective study.

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Section: Discussionmentioning

confidence: 99%

Analysis of the Number of Euploid Embryos in Preimplantation Genetic Testing Cycles With Early-Follicular Phase Long-Acting Gonadotropin-Releasing Hormone Agonist Long Protocol

Niu

et al. 2020

Front. Endocrinol.

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“…Several studies have aimed to investigate whether the FSH dose affects the embryo aneuploidy rate ( Barash et al. , 2017 ; Sekhon et al. , 2017 ; Wu et al.…”

Section: The More Oocytes the Better?mentioning

confidence: 99%

Individualized ovarian stimulation in IVF/ICSI treatment: it is time to stop using high FSH doses in predicted low responders

et al. 2019

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In IVF/ICSI treatment, the FSH starting dose is often increased in predicted low responders from the belief that it improves the chance of having a baby by maximizing the number of retrieved oocytes. This intervention has been evaluated in several randomized controlled trials, and despite a slight increase in the number of oocytes—on average one to two more oocytes in the high versus standard dose group—no beneficial impact on the probability of a live birth has been demonstrated (risk difference, −0.02; 95% CI, −0.11 to 0.06). Still, many clinicians and researchers maintain a highly ingrained belief in ‘the more oocytes, the better’. This is mainly based on cross-sectional studies, where the positive correlation between the number of retrieved oocytes and the probability of a live birth is interpreted as a direct causal relation. If the latter would be present, indeed, maximizing the oocyte number would benefit our patients. The current paper argues that the use of high FSH doses may not actually improve the probability of a live birth for predicted low responders undergoing IVF/ICSI treatment and exemplifies the flaws of directly using cross-sectional data to guide FSH dosing in clinical practice. Also, difficulties in the de-implementation of the increased FSH dosing strategy are discussed, which include the prioritization of intermediate outcomes (such as cycle cancellations) and the potential biases in the interpretation of study findings (such as confirmation or rescue bias).

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“…Indeed, earlier studies suggest that CS protocols may have a negative impact on the developmental and implantation potential of human embryos [reviewed in 2]. These results were challenged by other studies demonstrating that the degree of exposure to exogenous gonadotropins did not significantly modify the likelihood of blastocyst aneuploidy in patients with a normal ovarian response to stimulation [ 16 ]; relevantly, those earlier results were obtained from the analysis of cleavage stage embryos, so that the embryos aneuploidy rates were artificially increased by the inclusion of mosaic embryos with likely innate abilities to self-correct downstream beyond blastocyst stage (reviewed in [ 17 ]).…”

Section: Discussionmentioning

confidence: 99%

Mild ovarian stimulation with letrozole plus fixed dose human menopausal gonadotropin prior to IVF/ICSI for infertile non-obese women with polycystic ovarian syndrome being pre-treated with metformin: a pilot study

D’Amato

Caringella²,

Stanziano³

et al. 2018

Reprod Biol Endocrinol

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BackgroundLetrozole is widely employed as ovulation induction agent in women with PCOS, but its use in mild stimulation (MS) protocols for IVF is limited. Aim of the present study was to evaluate the feasibility of a MS protocol with letrozole plus hMG in non-obese PCOS women undergoing IVF after a metformin pre-treatment.MethodsWe retrospectively evaluated the data of 125 non-obese PCOS undergoing MS with letrozole plus hMG, 150 IU as starting dose, (group 1, N = 80) compared to those undergoing a conventional IVF stimulation protocols (CS) (group 2, N = 45) prior to IVF. All patients had received metformin extended release 1200–2000 mg daily for three to six months before IVF. GnRH antagonist was administered in both groups when the leading follicles reached 14 mm.ResultsBoth groups were comparable for age, BMI and ovarian reserve markers. Both groups showed lower than expected AFC and AMH values as a consequence of metformin pre-treatment. Letrozole-treated patients required a significantly lower amount of gonadotropins units (p < 0.0001), and showed significantly lower day 5, day 8 and hCG day E2 levels compared to patients undergoing the CS protocol (p < 0.0001, p < 0.0001 and p = 0.001 respectively). The oocyte yield, in terms of total (6, IQR 3, vs 6, IQR 4 respectively,) and MII oocytes (5, IQR 3, vs 5, IQR 3, respectively) number, did not differ among groups; the number of total (3, IQR 2, vs 3, IQR 1 respectively) and good quality embryos (2, IQR1 vs 2, IQR 1,5 respectively) obtained was comparable as well in the two groups. The number of fresh transfers was significantly higher in group 1 compared to group 2 (80% vs 60%, p = 0.016). A trend for higher cumulative clinical pregnancy rate was found in women undergoing MS compared to CS (42.5%vs 24,4%, p = 0.044), but the study was not powered to detect this difference.ConclusionsThe present study suggests that the use of letrozole as adjuvant treatment to MS protocols for IVF may be an effective alternative to CS protocols for non-obese PCOS patients pre-treated with metformin, as it provides comparable IVF outcome without requiring high FSH dose, and avoiding supraphysiological estradiol levels.

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The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response

Cited by 59 publications

References 36 publications

Analysis of the Number of Euploid Embryos in Preimplantation Genetic Testing Cycles With Early-Follicular Phase Long-Acting Gonadotropin-Releasing Hormone Agonist Long Protocol

Analysis of the Number of Euploid Embryos in Preimplantation Genetic Testing Cycles With Early-Follicular Phase Long-Acting Gonadotropin-Releasing Hormone Agonist Long Protocol

Individualized ovarian stimulation in IVF/ICSI treatment: it is time to stop using high FSH doses in predicted low responders

Mild ovarian stimulation with letrozole plus fixed dose human menopausal gonadotropin prior to IVF/ICSI for infertile non-obese women with polycystic ovarian syndrome being pre-treated with metformin: a pilot study

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