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Please note that the product information provided on this website is intended only for residents of the United States.

For ovulation induction/IUI cycles—

 

Add Crinone 8% to Support Endometrial Development, Implantation, and Pregnancy

 

Clomiphene citrate (CC) can have an antiestrogenic effect on the endometrium and cervical mucus

  • CC successfully induces ovulation in 50% to 75% of patients1,2 — but pregnancy rates are only 6% per cycle3
  • Dysynchronous endometrial transformation may result in deficient progestational effects in the late luteal phase1, including possible failed implantation2

 

 

Crinone 8% and estradiol correct the effects of CC

  • Higher incidence of normal endometrial development with CC + estradiol + Crinone 8%1

Study design: Results of a prospective, randomized trial of 37 women (aged 21–38 years) with oligo-amenorrhea who received ovulation induction with CC and IUI. Patients were randomized into 4 groups receiving either 50 mg (groups 1 and 2) or 100 mg (groups 3 and 4) of CC from cycle day 3–8. Groups 2 and 4 also received vaginal E2 cream 0.1 mg BID from day 8 until the LH surge and Crinone 8%, starting 3 days after ovulation. All participants had an endometrial biopsy performed 10 ± 1 days after ovulation.

 

*In-phase: ± 2 days of actual dating.

†Versus 50 mg CC + placebo (n=6).

‡Versus 100 mg CC + placebo (n=6).

 

Adding Crinone 8% and estradiol to CC may increase pregnancy rates

  • More than double the patients receiving Crinone 8% + estradiol + CC became pregnant versus patients receiving CC alone (17% versus 7%, respectively)7
  • Results are clinically different but are not statistically significant due to the small size of the study
Study design: Results of a randomized, open-label study of 71 oligo-ovulatory women. Patients were randomized into 1 of 2 groups—those who received only CC and those who received CC + hormonal supplementation (HS). All patients received 100 mg of CC from cycle days 3–7. Patients receiving HS started oral E2 at a dose of 1.5 mg BID on cycle day 8 and discontinued E2 at LH surge. Intercourse was encouraged starting on cycle day 10. Patients received Crinone 8% 3 days after LH surge and continued for 2 weeks or for a total of 12 weeks in case of pregnancy.

 

Click on the chart below for a larger view.

 

Schedule of therapy

  1. Clomiphene citrate 50 mg or 100 mg on days 3 to 7
  2. Estradiol 3 mg orally twice per day from day 8 to the morning of day 12
  3. Crinone 8% daily starting on day 17. If pregnancy occurs, continue for an additional 10 weeks

References: 1. Elkind-Hirsch KE, Phillips K, Bello SM, McNichol M, de Ziegler D. Sequential hormonal supplementation with vaginal estradiol and progesterone gel corrects the effect of clomiphene on the endometrium in oligo-ovulatory women. Hum Reprod. 2002;17:295–298. 2. Gerli S, Gholami H, Manna A, Di Frega AS, Vitiello C, Unfer V. Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study. Fertil Steril. 2000;73:85–89. 3. Bayer SR, Alper MM, Penzias AS. The Boston IVF Handbook of Infertility: a practical guide for practitioners who care for infertile couples. Boca Raton, FL: Parthenon; 2002. 4. Sereepapong W, Suwajanakorn S, Triratanachat S, et al. Effects of clomiphene citrate on the endometrium of regularly cycling women. Fertil Steril. 2000;73:287–291. 5. Dickey RP, Holtkamp DE. Development, pharmacology and clinical experience with clomiphene citrate. Hum Reprod. 1996;2:483–506. 6. Adashi EY, Rock JA, Rosenwaks Z, eds. Reproductive Endocrinology, Surgery, and Technology. Philadelphia, PA: Lippincott-Raven; 1996:1199–1201. 7. Elkind-Hirsch KE, Darensbourg C, Creasy G, Gipe D. Conception rates in clomiphene citrate cycles with and without hormone supplementation: a pilot study. Curr Med Res Opin. 2005;21:1035–1040.

 

Important Safety Information

The most common side effects of CRINONE (progesterone gel) 8% include breast enlargement, constipation, somnolence, nausea, headache, and perineal pain. CRINONE 8% is contraindicated in patients with active, or a history of, thrombophlebitis or thromboembolic disorders, patients who have known sensitivity to CRINONE 8%, missed abortion, undiagnosed vaginal bleeding, liver dysfunction or disease, and known or suspected malignancy of the breast or genital organs. Should any of the earliest manifestations of thrombotic disorders occur, the drug should be discontinued immediately. No adequate evidence is available to show that progesterone and progestins are effective in preventing miscarriage in women with a history of recurrent spontaneous pregnancy losses. The pretreatment physical exam should include special reference to breast and pelvic organs as well as a Papanicolaou smear. Nonfunctional causes of breakthrough bleeding should be considered, and for undiagnosed vaginal bleeding, diagnostic measures should be undertaken. Special care should be taken with patients who have conditions that may be influenced by fluid retention, those who have a history of psychic depression, and those with diabetes.