Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec 22:12:795254.
doi: 10.3389/fendo.2021.795254. eCollection 2021.

What Does Unexpected Suboptimal Response During Ovarian Stimulation Suggest, an Overlooked Group?

Bijun Wang  1 , Wenxia Liu  1 , Yi Liu  2 , Wen Zhang  1 , Chenchen Ren  3 , Yichun Guan  1
Affiliations

What Does Unexpected Suboptimal Response During Ovarian Stimulation Suggest, an Overlooked Group?

Bijun Wang et al. Front Endocrinol (Lausanne). .

Abstract

Unlike poor ovarian response, despite being predicted to be normal responders based on their ovarian reserve markers, many patients respond suboptimally to ovarian stimulation. Although we can improve the number of retrieved oocytes by increasing the recombinant FSH dose and adding LH, the effect of suboptimal ovarian response on cumulative live birth rate (CLBR) and offspring safety is unclear. This study focuses on the unexpected suboptimal response during ovulation induction, and its causes and outcomes are analysed for the first time with a large amount of data used to compare the cumulative pregnancy rate (CPR), CLBR and offspring safety of patients with one complete ART cycle with all embryos used. Our analysis included 5218 patients treated with the GnRH agonist long protocol for their first IVF-embryo transfer (ET) cycles. Patients were divided into two groups according to whether the ovarian response was suboptimal. Propensity score matching (PSM) was utilized for sampling at up to 1:1 nearest-neighbour matching with caliper 0.05 to balance the baseline and improve comparability between the groups. Results showed that age, BMI and basal FSH were independent risk factors for slow response; the initial dosage of Gn, FSH on the first day of Gn, and LH on the first day of Gn were independent protective factors for suboptimal response. Suboptimal responders were also more likely to have irregular menses. Regarding the clinical pregnancy rate of the fresh IVF/ICSI-ET cycles, the adjusted results of the two groups were not significantly different. There was no difference in the CPR, CLBR, or offspring safety-related data, such as gestational age, preterm delivery rate, birthweight, birth-height and Apgar Scores between the two groups after PSM. Age-related changes in the number of oocytes retrieved from women aged 20-40 years old between the two groups were different, indicating that suboptimal response in elderly patients suggests a decline in ovarian reserve. Although we can now improve the outcomes of suboptimal responders, it increases the cost to the patients and the time to live birth, which requires further attention.

Keywords: IVF; controlled ovarian stimulation; cumulative clinical pregnancy rate; cumulative live birth rate; suboptimal ovarian response.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the included population.
Figure 2
Figure 2
LH levels on the first day of Gn, the 8th day of Gn and the day of hCG injection in the suboptimal response group and normal response group. *means P < 0.05, NS means no statistical significance.
Figure 3
Figure 3
Age-related changes in the treatment outcomes of women aged 20–40 years in the normal ovarian response group and suboptimal ovarian response group.
See this image and copyright information in PMC

References

    1. Niederberger C, Pellicer A, Cohen J, Gardner DK, Palermo GD, O'Neill CL, et al. . Forty Years of IVF. Fertil Steril (2018) 110:185–324.e5. doi: 10.1016/j.fertnstert.2018.06.00 - DOI - PubMed
    1. Macklon NS, Stouffer RL, Giudice LC, Fauser BC. The Science Behind 25 Years of Ovarian Stimulation for In Vitro Fertilization. Endocr Rev (2006) 27:170–207. doi: 10.1210/er.2005-0015 - DOI - PubMed
    1. Gorgy A, Taranissi M. Defining and Predicting the Poor Responder! Fertil Steril (2001) 75:226–7. doi: 10.1016/s0015-0282(00)01689-7 - DOI - PubMed
    1. De Placido G, Mollo A, Alviggi C, Strina I, Varricchio MT, Ranieri A, et al. . Rescue of IVF Cycles by HMG in Pituitary Down-Regulated Normogonadotrophic Young Women Characterized by a Poor Initial Response to Recombinant FSH. Hum Reprod (2001) 16:1875–9. doi: 10.1093/humrep/16.9.1875 - DOI - PubMed
    1. De Placido G, Alviggi C, Perino A, Strina I, Lisi F, Fasolino A, et al. . Recombinant Human LH Supplementation Versus Recombinant Human FSH (rFSH) Step-Up Protocol During Controlled Ovarian Stimulation in Normogonadotrophic Women With Initial Inadequate Ovarian Response to rFSH. A Multicentre, Prospective, Randomized Controlled Trial. Hum Reprod (2005) 20:390–6. doi: 10.1093/humrep/deh625 - DOI - PubMed

Publication types

Substances