Mono-follicular Development – the Objective of Ovulation Induction with Follitropin beta Combined with Intrauterine Insemination

Authors: R. Středa 1;  J. Štěpán 1;  J. Tošner 2
Authors‘ workplace: Centrum asistované reprodukce SANUS, Pardubice, prim. MUDr. J. Štěpán, CSc. 1;  Gynekologicko-porodnická klinika, Fakultní nemocnice Hradec Králové, přednosta doc. MUDr. J. Tošner, CSc. 2
Published in: Ceska Gynekol 2008; 73(2): 93-97


To assess the effect of different starting follitropin’s beta dose (50 IU, 75 IU and 100 IU daily) for ovulation induction combined with intrauterine insemination on mono-follicular development.

Prospective study.

Centre for Assisted Reproduction SANUS, Pardubice.

Subject and method:
From March 2005 to November 2007 we performed a total number of 111 ovarian stimulations for patients with unexplained infertility, anovulatory disorder or mild male factor. We divided patients into groups based on patient’s response to clomifen citrate treatment. We examined follicular growth day 9 by transvaginal ultrasound and if necessary we adjusted gonadotropins’s dose.

We performed 104 intrauterine inseminations (94% of cycles with ovulation induction). We proved mono-follicular development in 36%, 37% and 36% (ns), number of follicles 1,9 ± 0,8, 2,2 ± 1,2 and 2,5 ± 1,8 (ns), endometrial thickness (mm) 8,5 ± 1,2, 8,6 ± 1,7 and 9,1 ± 1,8 (ns), total dose of rFSH (IU) 440 ± 156, 583 ± 154 and 830 ± 268 (p<0.001) in 50 IU, 75 IU and 100 IU follitropin’s beta groups. We achieved a total of 18 pregnancies (pregnancy rate 17%).

50 IU follitropin beta daily offers 36% probability of mono-follicular development. The disadvantage may be an increased risk of cycle cancellation due to low ovarian response. Daily doses 75 IU or 100 IU increase total consumption of rFSH.

Key words:
ovulation induction, intrauterine insemination, clomifene citrate, gonadotropins, follitropin beta, pregnancy rate, OHSS


1. Allegra, A., Marino, A, Coffaro, F., et al. GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy rates in IUI-stimulated cycles. A prospective randomized trial. Hum Reprod, 2006, 22, p. 101-108.

2. Arici, A., Byrd, W., Bradshaw, K., et al. Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles. Fertil Steril, 1994, 61, p. 314-318.

3. Balasch, J, Ballesca JL, Pimentel C, et al. Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles. Hum Reprod, 1994, 9, p. 1863-1866.

4. Barroso, G., Menocal, G., Felix, H., et al. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant follicle-stimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial. Fertil Steril, 2006, 86, p. 1428-1431.

5. Bedaiwy, MA., Forman, R., Mousa, NA., et al. Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation. Hum Reprod, 2006, 21, p. 2838-2844.

6. Calaf, AJ., Ruiz Balda, JA., Romeu, SA., et al. Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicentre, open trial. BJOG, 2003, 110, p. 1072-1077.

7. Cohlen, BJ., Vandekerckhove, P., te Velde, ER., et al. Timed intercourse versus intra-uterine insemination with or without ovarian hyperstimulation for subfertility in men. Cochrane.Database.Syst.Rev. 2000, CD000360.

8. Collins, J. Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. Current best evidence for the advanced treatment of unexplained subfertility. Hum Reprod, 2003, 18, p. 907-912.

9. Costello, MF. Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination. Aust NZJ Obstet Gynaecol, 2004, 44, p. 93-102.

10. Crosignani, PG., Somigliana, E. Effect of GnRH antagonists in FSH mildly stimulated intrauterine insemination cycles: a multicentre randomized trial. Hum Reprod, 2007, 22, p. 500-505.

11. Dankert, T., Kremer, JA., Cohlen, BJ., et al. A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility. Hum Reprod, 2007, 22, 3, p. 792-797.

12. Daya, S., Gunby, J. Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction. Hum Reprod, 1999, 14, p. 2207-2215.

13. Daya, S., Gunby, J. Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction cycles. Cochrane Database Syst Rev, 2000, CD002810.

14. Demirol, A., Gurgan, T. Comparison of different gonadotrophin preparations in intrauterine insemination cycles for the treatment of unexplained infertility: a prospective, randomized study. Hum Reprod, 2007, 22, p. 97-100.

15. Dickey, RP., Taylor, SN., Lu, PY., et al. Clomiphene citrate intrauterine insemination (IUI) before gonadotropin IUI affects the pregnancy rate and the rate of high-order multiple pregnancies. Fertil Steril, 2004, 81, p. 545-550.

16. Gerli, S., Casini, ML., Unfer, V., et al. Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness. Reprod Biomed Online, 2004, 9, p. 494-499.

17. Gerli, S., Casini, ML., Unfer, V., et al. Recombinant versus urinary follicle-stimulating hormone in intrauterine insemination cycles: a prospective, randomized analysis of cost effectiveness. Fertil Steril, 2004, 82, p. 573-578.

18. Hayden, CJ., Rutherford, AJ., Balen, AH. Induction of ovulation with the use of a starting dose of 50 units of recombinant human follicle-stimulating hormone (Puregon). Fertil Steril, 1999, 71, p. 106-108.

19. Hughes, EG. Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. ‘Effective treatment’ or ‘not a natural choice’? Hum Reprod, 2003, 18, p. 912-914.

20. Hugues, JN., Cedrin-Durnerin, I., Howles, CM., et al. use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study. Hum.Reprod. 2006, 21, p. 2817-22.

21. Isaza, V., Requena, A., Garcia-Velasco, JA., et al. Recombinant vs. urinary follicle-stimulating hormone in couples undergoing intrauterine insemination. A randomized study. J Reprod Med, 2003, 48, p. 112-118.

22. Khalil, MR., Rasmussen, PE., Erb, K., et al. Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles. Acta Obstet Gynecol Scand, 2001, 80, p. 74-81.

23. Lambalk, CB., Leader, A., Olivennes, F., et al. Treatment with the GnRH antagonist ganirelix prevents premature LH rises and luteinization in stimulated intrauterine insemination: results of a double-blind, placebo-controlled, multicentre trial. Hum Reprod, 2006, 21, p. 632-639.

24. Leader, A. Improved monofollicular ovulation in anovulatory or oligo-ovulatory women after a low-dose step-up protocol with weekly increments of 25 international units of follicle-stimulating hormone. Fertil Steril, 2006, 85, p. 1766-1773.

25. Levi Setti, PE. The importance of consistent FSH delivery in infertility treatment. Reprod Biomed Online, 2006, 12, p. 493-499.

26. Lopez, E., Gunby, J., Daya, S., et al. Ovulation induction in women with polycystic ovary syndrome: randomized trial of clomiphene citrate versus low-dose recombinant FSH as first line therapy. Reprod Biomed Online, 2004, 9, p. 382-390.

27. Messinis, IE. Ovulation induction: a mini review. Hum Reprod, 2005, 20, p. 2688-2697.

28. Palomba, S., Falbo, A., Orio, F. Jr., et al. A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod, 2005, 20, p. 2879-2886.

29. Papageorgiou, TC., Guibert, J., Savale, M., et al. Low dose recombinant FSH treatment may reduce multiple gestations caused by controlled ovarian hyperstimulation and intrauterine insemination. BJOG, 2004, 111, p. 1277-1282.

30. Platteau, P., Andersen, AN., Balen, A., et al. Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group II anovulatory infertility: a randomized controlled study. Hum Reprod, 2006, 21, p. 1798-1804.

31. Ragni, G., Alagna, F., Brigante, C., et al. GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages. Hum Reprod, 2004, 19, p. 54-58.

32. Ragni, G., Caliari, I., Nicolosi, AE., et al. Preventing high-order multiple pregnancies during controlled ovarian hyperstimulation and intrauterine insemination: 3 years’ experience using low-dose recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists. Fertil Steril, 2006, 85, p. 619-624.

33. Revelli, A., Poso, F., Gennarelli, G., et al. Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis. Reprod Biol Endocrinol, 2006, 4, p. 38.

34. Středa, R., Štěpán, J., Zadrobílková, I., et al. Indukce ovulace zvyšuje těhotenský index u intrauterinní inseminace. Čes Gynek, 2007, 64, s.159-163.

35. Verhulst, SM., Cohlen, BJ., Hughes, E., et al. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev, 2006, CD001838.

36. Williams, RS., Hillard, JB., De Vane, G., et al. A randomized, multicenter study comparing the efficacy of recombinant FSH vs recombinant FSH with Ganirelix during superovulation/IUI therapy. Am J Obstet Gynecol, 2004, 191, p. 648-651.

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