Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis

Capsule:
DNA sequencing and single nucleotide polymorphism association analyses in 2,271 endometriosis cases and 2,163 controls provide further evidence that variants in CYP2C19 contribute to endometriosis susceptibility in both familial and sporadic cases.

Authors:
Jodie N. Painter, Ph.D., Dale R. Nyholt, Ph.D., Lutz Krause, Ph.D., Zhen Z. Zhao, Ph.D., Brett Chapman, B.Sc., Christine Zhang, B.Sc. Hons., Sarah E. Medland, Ph.D. Nicholas G. Martin, Ph.D., Stephen H. Kennedy, Ph.D., Susan A. Treloar, Ph.D., Krina T. Zondervan, Ph.D., Grant W. Montgomery, Ph.D.

Volume 102, Issue 2, Pages 488–495.e3

Abstract:

Objective:
To evaluate the safety and efficacy of tamoxifen co-administration during conventional controlled ovarian hyperstimulation (COH) protocols for a fertility-preservation IVF cycle in breast cancer patients.

Design:
Two groups: retrospective descriptive cohort study and prospective study.

Setting:
Breast cancer oncology and fertility-preservation centers in a tertiary hospital.

Patient(s):
Two groups of breast cancer patients: premenopausal patients treated with adjuvant tamoxifen; and patients undergoing in vitro fertilization (IVF) for fertility preservation.

Intervention(s):
Fertility-preservation cycles, tamoxifen co-administration during conventional IVF.

Main Outcome Measure(s)
Endocrine records, and IVF results.

Result(s):
Estradiol (E2) levels were chronically high (mean 2663 pmol/L, maximum: 10,000 pmol/L) in 38 of 46 breast cancer patients treated with adjuvant tamoxifen. Co-administration of tamoxifen (48 cycles) during conventional IVF or without tamoxifen (26 cycles), using either the long gonadotropin-releasing hormone–agonist or–antagonist protocols, resulted, respectively, in a mean of 12.65 and 10.2 oocytes retrieved, and 8.5 and 6.4 embryos cryopreserved. Average peak E2 levels were 6,924 pmol/L and 5,093 pmol/L, respectively, but long-term recurrence risk (up to 10 years) was not increased.

Conclusion(s):
In breast cancer patients, co-administration of tamoxifen during conventional COH for fertility preservation does not interfere with IVF results. The high serum E2 levels during COH should be considered safe, as it simulates the high prevalence of persistently high serum E2 levels in premenopausal breast cancer patients safely treated with adjuvant tamoxifen.

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