Dataset Information

BRCA1 mutation carriers have a lower number of mature oocytes after ovarian stimulation for IVF/PGD.

ABSTRACT:

Purpose

The aim of this study was to determine whether BRCA1/2 mutation carriers produce fewer mature oocytes after ovarian stimulation for in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD), in comparison to a PGD control group.

Methods

A retrospective, international, multicenter cohort study was performed on data of first PGD cycles performed between January 2006 and September 2015. Data were extracted from medical files. The study was performed in one PGD center and three affiliated IVF centers in the Netherlands and one PGD center in Belgium. Exposed couples underwent PGD because of a pathogenic BRCA1/2 mutation, controls for other monogenic conditions. Only couples treated in a long gonadotropin-releasing hormone (GnRH) agonist-suppressive protocol, stimulated with at least 150 IU follicle stimulating hormone (FSH), were included. Women suspected to have a diminished ovarian reserve status due to chemotherapy, auto-immune disorders, or genetic conditions (other than BRCA1/2 mutations) were excluded. A total of 106 BRCA1/2 mutation carriers underwent PGD in this period, of which 43 (20 BRCA1 and 23 BRCA2 mutation carriers) met the inclusion criteria. They were compared to 174 controls selected by frequency matching.

Results

Thirty-eight BRCA1/2 mutation carriers (18 BRCA1 and 20 BRCA2 mutation carriers) and 154 controls proceeded to oocyte pickup. The median number of mature oocytes was 7.0 (interquartile range (IQR) 4.0-9.0) in the BRCA group as a whole, 6.5 (IQR 4.0-8.0) in BRCA1 mutation carriers, 7.5 (IQR 5.5-9.0) in BRCA2 mutation carriers, and 8.0 (IQR 6.0-11.0) in controls. Multiple linear regression analysis with the number of mature oocytes as a dependent variable and adjustment for treatment center, female age, female body mass index (BMI), type of gonadotropin used, and the total dose of gonadotropins administered revealed a significantly lower yield of mature oocytes in the BRCA group as compared to controls (p = 0.04). This finding could be fully accounted for by the BRCA1 subgroup (BRCA1 mutation carriers versus controls p = 0.02, BRCA2 mutation carriers versus controls p = 0.50).

Conclusions

Ovarian response to stimulation, expressed as the number of mature oocytes, was reduced in BRCA1 but not in BRCA2 mutation carriers. Although oocyte yield was in correspondence to a normal response in all subgroups, this finding points to a possible negative influence of the BRCA1 gene on ovarian reserve.

SUBMITTER: Derks-Smeets IAP

PROVIDER: S-EPMC5699993 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPredicting the number of oocytes retrieved (NOR) following controlled ovarian stimulation (COS) is the only way to ensure effective and safe treatment in assisted reproductive technology (ART). To date, there have been limited studies about predicting specific NOR, which hinders the development of individualized treatment in ART.ObjectiveTo establish an online tool for predicting NOR.Materials and methodsIn total, 621 prospective routine gonadotropin releasing hormone (GnRH) antagonist COS cycles were studied. Independent variables included age, body mass index, antral follicle counts, basal FSH, basal and increment of anti-mullerian hormone, Luteinizing hormon, estradiol, testosterone, androstenedione, and inhibin B. The outcome variable was NOR. The independent variables underwent appropriate transformation to achieve a better fit for a linear relationship with NOR. Pruned forward selection with holdback validation was then used to establish predictive models. Corrected Akaike's information criterion, Schwarz-Bayesian information criterion, scaled -log[likelihood], and the generalized coefficient of determination (R 2) were used for model evaluation.ResultsA multiple negative binomial regression model was used for predicting NOR because it fitted a negative binomial distribution. We established Model 1, using basal ovarian reserve markers, and Model 2, using both basal and early dynamic markers for predicting NOR following COS. The generalized R 2 values were 0.54 and 0.51 for Model 1 and 0.64 and 0.62 for Model 2 in the training and validation sets, respectively.ConclusionModels 1 and 2 could be applied to different scenarios. For directing the starting dose of recombinant follicle stimulation hormone (rFSH), Model 1 using basic predictors could be used prior to COS. Model 2 could be used for directing the adjustment of rFSH dosages during COS. An online tool (http://121.43.113.123:8002/) based on these two models is also developed. We anticipate that the clinical application of this tool could help the ART clinics to reduce iatrogenic ovarian under- or over-responses, and could reduce costs during COS for ART.