Effect of long-term combined oral contraceptive pill use on endometrial thickness

Obstet Gynecol. 2012 Aug;120(2 Pt 1):348-54. doi: 10.1097/AOG.0b013e31825ec2ee.


Objective: To estimate whether there is any association of long-term use of combined oral contraceptive pills (OCP) with adverse endometrial growth.

Methods: We reviewed the charts of 137 patients with history of OCP use undergoing endometrial preparation with estrogen for frozen embryo transfer. Endometrial thickness was measured by transvaginal ultrasonography on day 10 after menses and patients were divided into two groups (less than 7 mm and 7 mm or more).

Results: Thirty patients had endometrial thickness less than 7 mm and 107 had thickness of 7 mm or more. Mean years of combined OCP use in each group were 9.8±4.54 and 5.8±4.52, respectively (P<.001). With 10 years of combined OCP use as the threshold, the difference between the two groups (63.35% users in less than 7 mm group compared with 28.04% in the 7 mm or more thickness group) was highly significant (P<.001 by Fisher exact test), with an odds ratio of 4.43 (95% confidence interval 1.89-10.41). Past use of 5 years of OCPs was also associated with a significant (P=.002) difference in endometrial thickness. The mean endometrial thicknesses on cycle day 10 in patients using combined OCP for less than 10 years and 10 years or more were 9.54±1.88 mm and 8.48±2.33 mm, respectively, with P=.007. The mean endometrial thickness was 9.72±1.69 mm in less than 5 years and 8.81±2.23 mm in 5 or more years of use, respectively (P=.008). Cycle cancellation rates in the less than 7 mm group and 7 mm or greater endometrial thickness group were 23% and 4%, respectively (P=.002), but there was no difference in the clinical pregnancy rates between the two groups (13% compared with 27%, respectively; P=.15).

Conclusion: Long-term combined OCP use (5 years or more) can potentially affect optimal endometrial growth, leading to a higher cancellation rate and longer stimulation in frozen embryo transfer cycles. These findings suggest a previously unidentified adverse effect of long-term combined OCP use in women who are anticipating future fertility.

Level of evidence: II.

MeSH terms

  • Adult
  • Contraceptives, Oral, Hormonal / administration & dosage
  • Contraceptives, Oral, Hormonal / adverse effects*
  • Embryo Transfer / statistics & numerical data
  • Endometrium / drug effects*
  • Estradiol / therapeutic use
  • Estrogens / therapeutic use
  • Female
  • Humans
  • Infertility, Female / chemically induced
  • Retrospective Studies


  • Contraceptives, Oral, Hormonal
  • Estrogens
  • Estradiol