The effect of follicular phase length on cycle outcomes and endometrial development in gonadotrophin ovarian stimulation/intrauterine insemination cycles

Published:December 17, 2019DOI:


      Research question

      Does a shorter follicular phase length (FPL) affect cycle outcomes and endometrial development among women undergoing gonadotrophin ovarian stimulation/intrauterine insemination (OS/IUI)?


      Retrospective cohort study of 4773 OS/IUI cycles among 2054 patients. FPL was analysed first continuously, then dichotomously using an arbitrary cut-off at the 15th percentile (8 days) to divide cycles into shorter and longer FPL groups. Receiver operating characteristic (ROC) curves were constructed to further analyse the impact of FPL on all outcomes. Primary outcomes included clinical pregnancy, spontaneous abortion, multiple pregnancy and non-viable (ectopic/biochemical) pregnancy rates (CPR, SABR, MPR and NVPR, respectively). Secondary outcomes included endometrial thickness. All analyses controlled for age, day 3 FSH and body mass index.


      When analysing FPL continuously, CPR increased by 6.0% (adjusted odds ratio [aOR] 1.06, 95% CI 1.03–1.09, P < 0.001) with each additional follicular phase day. Similarly, in the dichotomous analysis, cycles with a longer FPL resulted in higher CPR with 45% higher odds of clinical pregnancy (aOR 1.45, 95% CI 1.07–1.97, P = 0.018). No effect of FPL was noted on NVPR, SABR or MPR. Endometrial thickness increased by 0.09 mm (95% CI 0.06–0.12, P < 0.001) with each additional FPL day and was increased in the longer compared with the shorter FPL group (adjusted mean difference 1.08 mm, 95% CI 0.81–1.34, P < 0.001).


      The data suggest that in gonadotrophin OS/IUI cycles, FPL might impact both chance of clinical pregnancy and endometrial thickness, independent of maternal age and ovarian reserve.


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        • Alport B.
        • Case A.
        • Lim H.
        • Baerwald A.
        Does the Ovarian Stimulation Phase Length Predict In vitro Fertilization Outcomes ?.
        Int. J. Fertil. Steril. 2011; 5: 134-141
        • Bromer J.G.
        • Aldad T.S.
        • Taylor H.S.
        Defining the proliferative phase endometrial defect.
        Fertil. Steril. 2009; 91: 698-704
        • Cédrin-Durnerin I.
        • Bstandig B.
        • Galey J.
        • Bry-Gauillard H.
        • Massin N.
        • Hugues J.N.
        Beneficial effects of GnRH agonist administration prior to ovarian stimulation for patients with a short follicular phase.
        Reprod. Biomed. Online. 2003; 7: 179-184
        • Check J.
        • Adelson H.
        • Lurie D.
        • Jamison T.
        Effect of the Short Follicular Phase on Subsequent Conception.
        Gynecol. Obstet. Investiation. 1992; 34: 180-183
        • Check J.
        • Liss J.
        • Shucoski M.
        Effect of short follicular phase with follicular maturity on conception outcome.
        Clin. Exp. Obstet. Gynecol. 2003; 30: 195-196
        • Esmailzadeh S.
        • Faramarzi M.
        Endometrial thickness and pregnancy outcome after intrauterine insemination.
        Fertil. Steril. 2007; 88: 432-437
        • Gonen Y.
        • Casper R.F.
        Prediction of implantation by the sonographic appearance of the endometrium during controlled ovarian stimulation for in vitro fertilization (IVF).
        J. In Vitro Fert. Embryo Transf. 1990; 7: 146-152
        • Jukic A.M.Z.
        • Weinberg C.R.
        • Baird D.D.
        • Wilcox A.J.
        Lifestyle and Reproductive Factors Associated with Follicular Phase Length.
        J. Women’s Heal. 2007; 16: 1340-1347
        • Kato I.
        • Toniolo P.
        • Koenig K.L.
        • Shore R.E.
        • Zeleniuch-Jacquotte A.
        • Akhmedkhanov A.
        • Riboli E.
        Epidemiologic correlates with menstrual cycle length in middle aged women.
        Eur. J. Epidemiol. 1999; 15: 809-814
        • Khalil M.R.
        • Rasmussen P.E.
        • Erb K.
        • Laursen S.B.
        • Rex S.
        • Westergaard L.G.
        Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles.
        Acta Obstet. Gynecol. Scand. 2001; 80 (–74): 74
        • Klein N.A.
        • Harper A.J.
        • Houmard B.S.
        • Sluss P.M.
        • Soules M.R.
        Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?.
        J. Clin. Endocrinol. Metab. 2002; 87: 5746-5750
        • Kovacs P.
        • Matyas S.
        • Boda K.
        • Kaali S.G.
        The effect of endometrial thickness on IVF/ICSI outcome.
        Hum. Reprod. 2003; 18: 2337-2341
        • Lenton E.A.
        • Landgren B.-M.
        • Sexton L.
        • Harper R.
        Normal variation in the length of the follicular phase of the menstrual cycle: effect of chronological age.
        Br. J. Obstet. An Int. J. Obstet. Gynaecol. 1984; 91: 681-684
        • Maher M.A.
        • Abdelaziz A.
        • Shehata Y.A.
        Effect of follicular diameter at the time of ovulation triggering on pregnancy outcomes during intrauterine insemination.
        Int. J. Gynecol. Obstet. 2017; 139: 174-179
        • Mardešič T.
        • Mannaerts B.
        • Abuzeid M.
        • Levy M.
        • Witjes H.
        • Fauser B.C.J.M.
        Short follicular phase of stimulation following corifollitropin alfa or daily recombinant FSH treatment does not compromise clinical outcome: A retrospective analysis of the Engage trial.
        Reprod. Biomed. Online. 2014; 28: 462-468
        • Martin J.R.
        • Mahutte N.G.
        • Arici A.
        • Sakkas D.
        Impact of duration and dose of gonadotrophins on IVF outcomes.
        Reprod. Biomed. Online. 2006; 13: 645-650
        • Mitwally M.F.M.
        • Casper R.F.
        Aromatase inhibition reduces the dose of gonadotropin required for controlled ovarian hyperstimulation.
        J. Soc. Gynecol. Investig. 2004; 11: 406-415
        • Noyes N.
        • Liu H.C.
        • Sultan K.
        • Schattman G.
        • Rosenwaks Z.
        Implantation: Endometrial thickness appears to be a significant factor in embryo implantation in in-vitro fertilization.
        Hum. Reprod. 1995; 10: 919-922
        • Richter K.S.
        • Bugge K.R.
        • Bromer J.G.
        • Levy M.J.
        Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos.
        Fertil. Steril. 2007; 87: 53-59
        • Sherman B.M.
        • Korenman S.G.
        Hormonal characteristics of the human menstrual cycle throughout reproductive life.
        J. Clin. Invest. 1975; 55: 699-706
        • Souter I.
        • Baltagi L.M.
        • Kuleta D.
        • Meeker J.D.
        • Petrozza J.C.
        Women, weight, and fertility: The effect of body mass index on the outcome of superovulation/intrauterine insemination cycles.
        Fertil. Steril. 2011; 95: 1042-1047
        • Treloar A.E.
        • Boynton R.E.
        • Behn B.G.
        • Brown B.W.
        Variation of the human menstrual cycle through reproductive life.
        Int. J. Fertil. Steril. 1967; 12: 77-126
        • Van Zonneveld P.
        • Scheffer G.J.
        • Broekmans F.J.M.
        • Blankenstein M.A.
        • De Jong F.H.
        • Looman C.W.N.
        • Habbema J.D.F.
        • Te Velde E.R.
        Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women.
        Hum. Reprod. 2003; 18: 495-501
        • Wolff E.F.
        • Bahidi N.
        • Alford C.
        • Richter K.
        • Widra E.
        Influences on endometrial development during intrauterine insemination: clinical experience of 2,929 patients with unexplained infertility.
        Fertil. Steril. 2013; 100: 194-199


      Jennifer Bakkensen received her BS from the University of North Carolina at Chapel Hill and MD from Weill Cornell Medical College. She is a resident in the Brigham and Women’s and Massachusetts General Hospital Residency in Obstetrics and Gynecology and plans to pursue a fellowship in Reproductive Endocrinology and Infertility.
      Key message
      This large-scale retrospective study suggests a possible relationship, independent of age and ovarian reserve, between follicular phase length, endometrial thickness and clinical pregnancy rates, specifically among women undergoing gonadotrophin-induced OS/IUI, an important first-line infertility treatment. These findings may help physicians in counselling their patients on the likelihood of successful OS/IUI treatment.