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Optimal lead follicle size in letrozole human menopausal gonadotrophin intrauterine insemination cycles with and without spontaneous LH surge

  • Author Footnotes
    1 Contributed equally.
    Li Chen
    Footnotes
    1 Contributed equally.
    Affiliations
    Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine Shanghai, People's Republic of China
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally.
    Shutian Jiang
    Correspondence
    Corresponding author.
    Footnotes
    1 Contributed equally.
    Affiliations
    Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine Shanghai, People's Republic of China
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally.
    Qianwen Xi
    Footnotes
    1 Contributed equally.
    Affiliations
    Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine Shanghai, People's Republic of China
    Search for articles by this author
  • Wenzhi Li
    Affiliations
    Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine Shanghai, People's Republic of China
    Search for articles by this author
  • Qifeng Lyu
    Correspondence
    Corresponding author.
    Affiliations
    Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine Shanghai, People's Republic of China
    Search for articles by this author
  • Yanping Kuang
    Correspondence
    Corresponding author.
    Affiliations
    Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine Shanghai, People's Republic of China
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally.
Published:November 06, 2022DOI:https://doi.org/10.1016/j.rbmo.2022.11.003

      Abstract

      Research question

      What is the optimal lead follicle size in letrozole, human menopausal gonadotrophin and intrauterine insemination (IUI) cycles with and without spontaneous LH surges?

      Design

      This retrospective cohort study included 3797 letrozole HMG IUI cycles between January 2010 and May 2021. All cycles were divided into two groups: the HCG trigger group (trigger day LH ≤15 mIU/ml) and the spontaneous LH surge group (trigger day LH >15 mIU/ml). These two groups were subdivided into smaller groups based on the diameter of the follicles. The primary outcome measure was clinical pregnancy rate. Logistic regression analysis was conducted to explore other risk factors.

      Results

      In the HCG trigger group, the clinical pregnancy rate varied significantly, with rates of 20.8%, 14.9% and 11.8% for the 16.1–18.0, 18.1–20.0 and 20.1–22.0 mm groups, respectively (P = 0.005). In the spontaneous LH surge group, the pregnancy rate of follicles within 14.1–16.0 mm was significantly higher than that of follicles within 20.1–22.0 mm (adjusted OR 0.533, 95% CI 0.308 to 0.923, P = 0.025). Also, patients with two lead follicles were 2.569 times more likely to achieve a clinical pregnancy than those with only one lead follicle (adjusted OR 2.569, 95% CI 1.258 to 5.246, P = 0.010). The duration of infertility was also found to be a common influencing factor in both groups.

      Conclusions

      The optimal lead follicle size was between 16.1 and 18.0 mm in HCG-triggered letrozole HMG IUI cycles. If the lead follicle size is relatively small (14.1–18.0 mm) when a spontaneous LH surge occurs, there is no need to cancel the IUI cycle.

      KEYWORDS

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      References

        • Ahinko-Hakamaa K.
        • Huhtala H.
        • Tinkanen H.
        Success in intrauterine insemination: the role of etiology.
        Acta Obstetricia et Gynecologica Scandinavica. 2007; 86: 855-860
        • Ashrafi M.
        • Daghighi S.
        • Pourasghari P.
        • Zolfaghari Z.
        The Role of Infertility Etiology in Success Rate of Intrauterine Insemination Cycles: An Evaluation of Predictive Factors for Pregnancy Rate.
        Int. J. Fertil. Steril. 2013; 7: 100-107
        • Bedaiwy M.A.
        • Abdelaleem M.A.
        • Hussein M.
        • Mousa N.
        • Brunengraber L.N.
        • Casper R.F.
        Hormonal, follicular and endometrial dynamics in letrozole-treated versus natural cycles in patients undergoing controlled ovarian stimulation.
        Reproductive Biology and Endocrinology. 2011; 9: 83
        • Bedaiwy M.A.
        • Mousa N.A.
        • Esfandiari N.
        • Forman R.
        • Casper R.F.
        Follicular Phase Dynamics with Combined Aromatase Inhibitor and Follicle Stimulating Hormone Treatment.
        The Journal of Clinical Endocrinology & Metabolism. 2007; 92: 825-833
        • Carson S.A.
        • Kallen A.N.
        Diagnosis and Management of Infertility: A Review.
        JAMA. 2021; 326: 65
        • Dickey R.P.
        • Taylor S.N.
        • Lu P.Y.
        • Sartor B.M.
        • Rye P.H.
        • Pyrzak R.
        Effect of diagnosis, age, sperm quality, and number of preovulatory follicles on the outcome of multiple cycles of clomiphene citrate-intrauterine insemination.
        Fertility and Sterility. 2002; 78: 1088-1095
        • Elnashar A.
        • Fouad H.
        • Eldosoky M.
        • Saeid N.
        Letrozole induction of ovulation in women with clomiphene citrate–resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio.
        Fertility and Sterility. 2006; 85: 511-513
        • -E.-A. Elsedeek M.S.
        • Elmaghraby H.A.H.
        Predictors and characteristics of letrozole induced ovulation in comparison with clomiphene induced ovulation in anovulatory PCOS women.
        Middle East Fertility Society Journal. 2011; 16: 125-130
        • Farhi J.
        • Orvieto R.
        • Gavish O.
        • Homburg R.
        The association between follicular size on human chorionic gonadotropin day and pregnancy rate in clomiphene citrate treated polycystic ovary syndrome patients.
        Gynecological Endocrinology. 2010; 26: 546-548
        • Gao Y.
        • Jiang S.
        • Chen L.
        • Xi Q.
        • Li W.
        • Zhang S.
        • Kuang Y.
        The pregnancy outcomes of infertile women with polycystic ovary syndrome undergoing intrauterine insemination with different attempts of previous ovulation induction.
        Front Endocrinol. (Lausanne). 2022; 13: 922605
        • George K.
        • Nair R.
        • Tharyan P.
        Ovulation triggers in anovulatory women undergoing ovulation induction.
        in: Collaboration T.C. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2008 (pp. CD006900.pub006902)
        • Ghosh C.
        • Buck G.
        • Priore R.
        • Wacktawski-Wende J.
        • Severino M.
        Follicular response and pregnancy among infertile women undergoing ovulation induction and intrauterine insemination.
        Fertility and Sterility. 2003; 80: 328-335
        • Goverde A.J.
        • McDonnell J.
        Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost- effectiveness analysis.
        THE LANCET. 2000; 355: 6
        • Hancock K.L.
        • Pereira N.
        • Christos P.J.
        • Petrini A.C.
        • Hughes J.
        • Chung P.H.
        • Rosenwaks Z.
        Optimal lead follicle size for human chorionic gonadotropin trigger in clomiphene citrate and intrauterine insemination cycles: an analysis of 1,676 treatment cycles.
        Fertility and Sterility. 2021; 115: 984-990
        • Hansen K.R.
        • He A.L.W.
        • Styer A.K.
        • Wild R.A.
        • Butts S.
        • Engmann L.
        • Diamond M.P.
        • Legro R.S.
        • Coutifaris C.
        • Alvero R.
        • Robinson R.D.
        • Casson P.
        • Christman G.M.
        • Huang H.
        • Santoro N.
        • Eisenberg E.
        • Zhang H.
        Predictors of pregnancy and live-birth in couples with unexplained infertility after ovarian stimulation–intrauterine insemination.
        Fertility and Sterility. 2016; 105 (e1572): 1575-1583
        • Healey S.
        • Tan S.L.
        • Tulandi T.
        • Biljan M.M.
        Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination.
        Fertility and Sterility. 2003; 80: 1325-1329
        • Maher M.A.
        • Abdelaziz A.
        • Shehata Y.A.
        Effect of follicular diameter at the time of ovulation triggering on pregnancy outcomes during intrauterine insemination.
        International Journal of Gynecology & Obstetrics. 2017; 139: 174-179
        • Merviel P.
        • Heraud M.H.
        • Grenier N.
        • Lourdel E.
        • Sanguinet P.
        • Copin H.
        Predictive factors for pregnancy after intrauterine insemination (IUI): An analysis of 1038 cycles and a review of the literature.
        Fertility and Sterility. 2010; 93: 79-88
        • Nandi A.
        • Chen Z.
        • Patel R.
        • Poretsky L.
        Polycystic ovary syndrome.
        Endocrinol. Metab. Clin. North Am. 2014; 43: 123-147
        • Palatnik A.
        • Strawn E.
        • Szabo A.
        • Robb P.
        What is the optimal follicular size before triggering ovulation in intrauterine insemination cycles with clomiphene citrate or letrozole? An analysis of 988 cycles.
        Fertility and Sterility. 2012; 97 (e1083): 1089-1094
        • Penzias A.
        • Bendikson K.
        • Falcone T.
        • Hansen K.
        • Hill M.
        • Jindal S.
        • Mersereau J.
        • Racowsky C.
        • Rebar R.
        • Steiner A.Z.
        • Stovall D.
        • Tanrikut C.
        • Kalra S.
        • Reindollar R.
        • Hurd W.
        Evidence-based treatments for couples with unexplained infertility: a guideline.
        Fertility and Sterility. 2020; 113: 305-322
      1. Plosker, S. M., Jacobson, W., & Amato, P. Predicting and optimizing success in an intra-uterine insemination programme. 1994: 8.

        • Qin F.
        • Zhou Y.
        • Huan L.
        • Gui W.
        Comparison of clomiphene and letrozole for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A systematic review and meta-analysis.
        Medicine. 2020; 99: e21006
        • Requena A.
        • Herrero J.
        • Landeras J.
        • Navarro E.
        • Neyro J.L.
        • Salvador C.
        • Tur R.
        • Callejo J.
        • Checa M.A.
        • Farre M.
        • Espinos J.J.
        • Fabregues F.
        • Grana-Barcia M.
        • G.o.t.S.S.o Fertility R.E.I.
        Use of letrozole in assisted reproduction: a systematic review and meta-analysis.
        Human Reproduction Update. 2008; 14: 571-582
        • Sahakyan M.
        • Harlow B.L.
        • Hornstein M.D.
        Influence of age, diagnosis, and cycle number on pregnancy rates with gonadotropin-induced controlled ovarian hyperstimulation and intrauterine insemination.
        Fertility and Sterility. 1999; 72: 500-504
        • Salha O.
        • Nugent D.
        • Dada T.
        • Kaufmann S.
        • Levett S.
        • Jenner L.
        • Lui S.
        • Sharma V.
        The relationship between follicular fluid aspirate volume and oocyte maturity in in-vitro fertilization cycles.
        Human Reproduction. 1998; 13: 1901-1906
        • Shalom-Paz E.
        • Marzal A.
        • Wiser A.
        • Hyman J.
        • Tulandi T.
        Does optimal follicular size in IUI cycles vary between clomiphene citrate and gonadotrophins treatments?.
        Gynecological Endocrinology. 2014; 30: 107-110
        • Stone B.A.
        • Vargyas J.M.
        • Ringler G.E.
        • Stein A.L.
        • Marrs R.P.
        Determinants of the outcome of intrauterine insemination: Analysis of outcomes of 9963 consecutive cycles.
        American Journal of Obstetrics and Gynecology. 1999; 180: 1522-1534
        • Tamura I.
        • Kawamoto-Jozaki M.
        • Fujimura T.
        • Doi-Tanaka Y.
        • Takagi H.
        • Shirafuta Y.
        • Mihara Y.
        • Taketani T.
        • Tamura H.
        • Sugino N.
        Relationship between follicular size and developmental capacity of oocytes under controlled ovarian hyperstimulation in assisted reproductive technologies.
        Reproductive Medicine and Biology. 2021; 20: 299-304

      Biography

      Kuang Yanping MD, PhD, is Director of the Department of Assisted Reproductive Medicine at Shanghai Ninth People's Hospital. He is Chairman of the Professional Committee on Reproductive Health, China Association of Rehabilitation Medicine, and Vice Chairman of the Reproductive Medicine branch, China International Exchange and Promotive Association for Medical and Health Care.
      Key message
      The optimal lead follicle size with better odds of clinical pregnancy was between 16.1 and 18.0 mm in HCG-triggered letrozole and HMG IUI cycles. If the lead follicle size is relatively small (14.1–18.0 mm) when a spontaneous LH surge occurs, there is no need to cancel the IUI cycle.