Dataset Information

Association of bioavailable inhibin B and oocyte yield in controlled ovarian stimulation.

ABSTRACT:

Objective

To determine if the biologically active or bioavailable inhibin B (bio-inhB) correlated with the oocyte yield in controlled ovarian stimulation (COS).

Design

Cross-sectional study.

Setting

Academic center.

Patients

Women undergoing oocyte cryopreservation.

Interventions

None.

Main outcome measures

Serum of women were sampled to measure bio-inhB at three points: baseline ("start"); middle ("mid"); and end of COS. A validated, highly specific enzyme-linked immunosorbent assay (Ansh Labs, Webster, TX) measured bio-inhB. The Spearman tests analyzed correlations between bio-inhB and other ovarian reserve markers, including age, follicle-stimulating hormone (FSH), antral follicle count (AFC), and antimüllerian hormone (AMH), and correlations between these markers and oocyte yield.

Results

A total of 144 women were included. Bioavailable inhibin B at the mid and end of COS, plus its delta, were strongly correlated with other ovarian reserve markers. As the bio-inhB concentration increased, the AFC and AMH levels also increased, whereas the FSH concentration and age decreased. Bioavailable inhibin B values, except at the start of COS, were more strongly correlated with oocyte yield than the FSH concentration (r = 0.72-0.82 vs. r = -0.44) and correlated similarly to the AFC and AMH concentration (r = 0.79 and 0.81, respectively). These correlations strengthened in those with diminished ovarian reserve, specifically age ≥35 years or AMH concentration <2 ng/mL (r = 0.71-0.86 vs. r = 0.49-0.67).

Conclusions

Predicting COS outcome is imperfect. When using a highly specific enzyme-linked immunosorbent assay, bio-inhB correlated with the oocyte yield similar to or more strongly than traditionally used ovarian reserve markers. These correlations strengthened in cases of diminished ovarian reserve. Bioavailable inhibin B provides physicians with an additional clinical tool for estimating COS outcome.

SUBMITTER: Danis RB

PROVIDER: S-EPMC8267401 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of bioavailable inhibin B and oocyte yield in controlled ovarian stimulation.

Danis Rachel B RB Sriprasert Intira I Ho Jacqueline R JR McGinnis Lynda K LK Kumar Ajay A Stanczyk Frank Z FZ

F&S reports 20210331 2

<h4>Objective</h4>To determine if the biologically active or bioavailable inhibin B (bio-inhB) correlated with the oocyte yield in controlled ovarian stimulation (COS).<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>Academic center.<h4>Patients</h4>Women undergoing oocyte cryopreservation.<h4>Interventions</h4>None.<h4>Main outcome measures</h4>Serum of women were sampled to measure bio-inhB at three points: baseline ("start"); middle ("mid"); and end of COS. A validated, highly specific en ...[more]

PMID: 34278353

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Project description:Study questionHow much variation in oocyte yield after controlled ovarian stimulation (COS) can be accounted for by known patient and treatment characteristics?Summary answerThere is substantial variation in the COS responses of similar women and in repeated COS episodes undertaken by the same woman, which cannot be accounted for at present.What is already knownThe goal of individualized COS is to safely collect enough oocytes to maximize the chance of success in an ART cycle. Personalization of treatment rests on the ability to reduce variation in response through modifiable factors.Study design size durationMultilevel modelling of a routine ART database covering the period 1 October 2008-8 August 2012 was employed to estimate the amount of variation in COS response and the extent to which this could be explained by immutable patient characteristics and by manipulable treatment variables. A total of 1851 treatment cycles undertaken by 1430 patients were included. The study was not subject to attrition, as cancelled cycles were included in the analysis.Participants/materials setting methodsWomen aged 21-43 years undergoing ovarian stimulation for IVF (possibly with ICSI) using their own eggs at a tertiary care centre.Main results and the role of chanceSubstantial unexplained variation in COS response (oocyte yield): was observed (3.4-fold (95% CI: 3.12 to 3.61)). Only a relatively small amount of this variation (around 19%) can be explained by modifiable factors. A significant, previously undescribed predictor of response was the practitioner performing oocyte retrieval, with 1.5-fold variation between surgeons with the highest and lowest yields.Limitations reasons for cautionAlthough a large number of covariables were adjusted for in the analysis, including those that were used for dosing and determination of the stimulation regimen, this study is subject to confounding due to unmeasured variables and measurement error.Wider implications of the findingsThe present study suggests that there are limits to the extent that COS response can be predicted on the basis of known factors, or controlled by manipulation of treatment factors. Moreover, modifiable variation in response appears to be partially attributable to differences between surgeons performing oocyte retrieval. Consequently, consistent prevention of ineffective or unsafe responses to COS is not likely to be possible at present. Our results highlight the importance of blinding surgeons in RCTs. The data also suggest that there is likely to be limited scope for personalized treatment unless additional predictors of ovarian response can be identified.Study funding/competing interestsJ.W. is funded by a Doctoral Research Fellowship from the National Institute for Health Research (DRF-2014-07-050) supervised by S.A.R. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. J.W. is a statistical editor of the Cochrane Gynaecology and Fertility Group. S.A.R. is a statistical editor for Human Reproduction. J.W. also declares that publishing peer-reviewed articles benefits his career. A.L.M. has received consultation fees from MSD, Merck Serono, Ferring, TEVA, Roche, Beckman Coulter.

Project description:The number of mature oocytes is a key factor in the success of Assisted Reproductive Techniques (ART). Exogenous gonadotropins are administered during ovarian stimulation in order to maximize the number of oocytes available for fertilization. During stimulation, monitoring is mandatory to evaluate individual response, to avoid treatment complications and assist in the determination of the optimal day for final oocyte maturation and oocyte retrieval. Routine monitoring during stimulation includes transvaginal ultrasound examinations and measurement of serum estradiol (E2). Due to multifollicular growth of follicles of varying size, serum E2 levels are commonly supraphysiological and often variable, rendering E2-measurement during ovarian stimulation unreliable as a determinant of oocyte maturity. In contrast to serum E2, serum Inhibin A levels increase once a minimum follicle size of 12-15 mm is achieved. Due to this fact, serum Inhibin A levels could present in combination with ultrasound monitoring a more reliable parameter to determine the optimal follicle size for final oocyte maturation, as only follicles with a size of 12 mm and beyond will contribute to the serum Inhibin A level. This prospective observational, cross-sectional study demonstrates, that on the day of final oocyte maturation serum Inhibin A is strongly correlated to the number of follicles ≥15 mm (0.72) and to the number of retrieved and mature oocytes (ρ 0.82/0.77, respectively), whereas serum E2 is moderately correlated to the parameters mentioned above (ρ 0.64/0.69/0.69, respectively). With an area under the curve (AUC) of 0.91 for Inhibin A, compared to an AUC of 0.84 for E2, Inhibin A can be regarded as a better predictor for the optimal timing of trigger medication with a threshold number of ≥10 mature oocytes. It can be concluded from this data that serum Inhibin A in combination with transvaginal ultrasound monitoring may be a more powerful tool in the decision making process on trigger timing as compared to E2.

Project description:While gonadotrophin releasing hormone (GnRH) antagonists have been the standard of pituitary suppression during ovarian stimulation for ART, progestin primed ovarian stimulation (PPOS) has emerged as an alternative. Progestins can be started simultaneously with gonadotrophins (fixed PPOS) or later in the cycle depending on follicle growth (flexible PPOS). However, the flexible and fixed PPOS regimens have not been directly compared as of yet. This was a retrospective cohort study including women with diminished ovarian reserve who underwent oocyte cryopreservation. All women underwent ovarian stimulation with a fixed 300 IU daily dose of FSH. The primary outcome was the number of MII oocyte retrieved per cycle. Secondary outcome measures included the incidence of premature LH surge (>10ng/mL) and number of follicles larger than 14mm on the day of maturation trigger. During the screening period 2 out of 97 cycles were cancelled before oocyte retrieval, one in each group yielding an overall cancelation rate of 2%. Among women who had oocyte retrieval, 65 underwent flexible and 30 fixed PPOS. At baseline women on fixed and flexible PPOS had similar age (mean difference: -2.17 years, 95% CI: -4.46 to 0.11) and serum AMH levels (mean difference: 0.10 ng/mL, 95% CI: -0.24 to 0.47). Slight imbalances between the groups were rectified with propensity score matching using age and AMH levels. The incidence of premature LH surge (RR: 1.47, 95% CI: 0.51 - 5.27, p = 0.50), follicle count larger than 14mm on hCG day (RR: 1.14, 95% CI: 0.93 - 1.42, p = 0.22), number of MII oocytes retrieved (RR: 0.95, 95% CI: 0.79 - 1.15, p = 0.61) were similar between flexible and fixed PPOS. The rate of no oocyte retrieval was same between the groups (0.0% both) but no formal estimation was possible. Flexible and fixed PPOS regimens had no appreciable differences regarding MII oocyte yield and the incidence of premature LH surges. Cycles without oocyte retrieval were rare in both groups and ultrasonographic parameters of gonadotropin response were similar. Our study suggests the performances of either progestin regimen are comparable in this group of women.

Project description:Background: Prior studies have shown that patients with a >10% estradiol (E2) rise after trigger had more oocytes retrieved than plateauing or decreasing E2 responders. However, multiple follicles develop at different stages of maturation during controlled ovarian stimulation (COS) and may exhibit different responses to trigger. The association between the magnitude of E2 increase and oocyte retrieval outcomes is still unclear. Methods: This was a retrospective cohort study of 2,898 women undergoing their first COS cycles with normal response from January 2014 to December 2017 at a tertiary-care academic medical center. Patients were categorized into five groups according to the percentage increase in E2 levels before and after dual trigger: <10.0%, 10.0-19.9%, 20.0-29.9%, 30.0-39.9%, and ≥40.0%. Univariable and multivariable linear regression analysis were performed to explore the association between E2 increase and oocyte/mature oocyte yield, while logistic regression was used to assess its effect on low oocyte/mature oocyte yield (<10th percentile). Results: The post-trigger E2 increase was negatively associated with both oocyte yield (P-trend < 0.001, adjusted P-trend = 0.033) and mature oocyte yield (P-trend < 0.001, adjusted P-trend = 0.002). Compared with a <10.0% E2 increase after trigger, patients with a ≥40.0% rise had fewer mature oocyte yield [adjusted mean absolute difference [MD] = -5.2, 95% confidence interval [CI]: -8.2--1.8] and higher risk of low mature oocyte yield (adjusted odds ratio [OR] = 1.64, 95% CI: 1.04-2.60), whereas no statistical significance was found in oocyte yield (adjusted MD = -2.7, 95% CI: -6.1-0.8) and low oocyte yield (adjusted OR = 1.48, 95% CI: 0.96-2.28). In addition, the rates of implantation, positive pregnancy test, clinical pregnancy, ongoing pregnancy, pregnancy loss, and live birth were comparable among the 1,942 frozen embryo transfer cycles with embryos originating from different groups of E2 increase (all P > 0.05). Conclusions: A higher E2 rise after dual trigger is independently associated with a lower oocyte and mature oocyte yield in normal responders. Further studies are needed to explore the efficacy of individualized time interval from trigger to oocyte retrieval based on the magnitude of E2 increase after trigger.

Dataset Information

Association of bioavailable inhibin B and oocyte yield in controlled ovarian stimulation.

Objective

Design

Setting

Patients

Interventions

Main outcome measures

Results

Conclusions

Publications

Association of bioavailable inhibin B and oocyte yield in controlled ovarian stimulation.

Similar Datasets

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