Cover
Vol. 8 No. 1 (2018)

Published: June 30, 2018

Pages: 29-37

Research Article

Role of Low-Dose Human Chorionic Gonadotropin Following Clomiphene Citrate in Folliculogenesis and Ovulation in Infer-tile Women

Omaima I. Khalaf 1 Manal T. Al-Obaidi Lubna A. Al-Anbari
1High Institute of Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University, Baghdad-IRAQ
History
  • Received: March 1, 2018
  • Available Online: June 1, 2018

Abstract

Background:Ovulation disorders, usually presents as menstrual disturbance, are the cause of infertility in around 25% of couples who have difficulty to conceive. The drug most commonly prescribed for the induction of ovulation is clomiphene citrate (CC). If the patient does not ovulate after the use of CC, the choice was to add gonadotropins. Gonadotropin therapy is very expensive with significant risks of high order multiple gestations and ovarian hyperstimulation syndrome. Human chorionic gonadotropin hCG can function as a surrogate for LH and oc-cupies LH receptors for more than 24 hours allowing prolonged stimulation also it has longer half-life and greater affinity for the LH receptor. Objective: The purpose of this study was to compare the effectiveness of low-dose human chorionic gonadotropin (hCG) in the late follicular phase to induce ovulation in clomifene citrate resistant patients who had previously failed to ovulate on clomiphene citrate (CC) alone. Subjects,Materials and Methods: A total of 71 patients who attend infertility clinic in the High Institute of Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University, where prospectively randomly assigned into two groups. hCG Group received 100 mg dose of CC from day 5 of men-strual cycle for 5 days, then each patient received 200 IU hCG (DICLAIR®) subcutaneous injection daily when the largest follicle mean diameter was 12 mm or larger starting on day twelve of menstrual cycle. Non-hCG group received 150 mg dose of CC from day 5 of menstrual cycle for 5 days, and both groups were monitored with transvaginal ultrasound. Ultrasound measurements of follicle number and growth, ovulation, endometrial thickness and pattern were recorded and compared between the two groups. Student t test and fisher exact test were used for statistical comparison between the two groups. Results: The low-dose hCG group had significantly higher percentage of ovula-tory cycles (80% vs 44.4% P value 0.006). There was no significant difference in the endometrial thickness between the groups but it appears higher in hCG group (10.55±1.82 vs. 9.62 ± 1.87 in non-hCG group, p value 0.056). Non significant but higher incidence of echogenic (luteinized) endometrium 48 hour post ovula-tion in hCG group (36/40 (90%) vs. 20/25 (80%) for non-hCG group p-value = 0.288). Conclusions: The use of low-dose hCG after CC in the late follicular phase re-sults in continued follicle growth, higher ovulation rate. This treatment offers an efficient and cost-effective alternative before gonadotropin therapy for this type of patients.

Keywords

References

  1. Kuohung.W, Mark. D. H, Robert .L, Barbieri, Vanessa. A. Evaluation of fe- male Infertility. Last literature review 2009; version 17.3.
  2. Practice Committee of the American Society for Reproductive Medicine. Defi- nitions of infertility and recurrent preg- nancy loss. Fertil Steril 2008; 90(5 Sup- pl): S60.
  3. Plouffe L.Jr. Selective estrogen re- ceptor modulators (SERMs) in clinical practice. J. Soc Gynecol Investig.2000. Jan-Feb;7(1, Suppl) S38–S46 .
  4. Sovino.H, Sir-Petermann.T, Devoto.L. Clomiphene citrate and ovulation induc- tion. Reprod Biol Med. 2002; pp. 303- 310.
  5. Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized double-blind comparison of the effects of clomi- phene citrate and the aromatase inhibitor letrozole on ovulatory function in nor- mal women.Fertil Steril 2002; 78: 280– 5.
  6. Griesinger G, von OS, Schultze-Mos- gau A et al. Follicular and endocrine re- sponse to anastrozole versus clomiphene citrate administered in follicular phase to normoovulatory women. A random- ized comparison. Fertil Steril 2009; 91: 1831–6.
  7. Dehbashi S, Vafaei H, Parsanezhad MD, Alborzi S. Time of initiation of clo- miphene citrate and pregnancy rate in polycystic ovarian syndrome. Interna- tional Journal of Gynecology and Obstet- rics. 2006;93(1):44-8.
  8. Favaedi M, Taheripanah R, Kabir sal- mani M. Evaluation of endometrial mor- phology by scanning electron microsco- py on the clomiphene citrate comparison with clomiphene citrate plus Estradiol Valerate and clomiphene plus proges- terone in infertile women. Internation- al journal of reproductive biomedicine. 2009;7(2).
  9. Ezcurra D, Humaidan P.. A review of luteinising hormone and human cho- Iraqi Journal Of Embryos and Infertility Researches Vol.(8) Issue-1 (2018) rionic gonadotropin when used in assist- ed reproductive technology. Reprod Biol Endocrinol (2014) 12:95.10.1186/1477- 7827-12-95 [PMC free article] [PubMed] [Cross Ref
  10. Santi D., Casarini L., Alviggi C., Si- moni M. Efficacy of Follicle-Stimulating Hor- mone (FSH) Alone, FSH + Luteinizing Hormone, Human Menopausal Gonad- otropin or FSH + Human Chorionic Go- nadotropin on Assisted Reproductive Technology Outcomes in the “Person- alized” Medicine Era: A Meta-analy- sis. Front Endocrinol (Lausanne). 2017 Jun 1;8:114..2017.00114. eCollection 2017
  11. Wong PC, Qiao J, Ho C, Ramaraju GA, Wiweko B, Takehara Y, et al. Cur- rent opinion on use of luteinizing hor- mone supplementation in assisted repro- duction therapy: An Asian perspective. Reprod Biomed Online.2011;23:81–90. [PubMed]
  12. Cole, Laurence A. “Biological Func- tions of hCG and hCG-Related Mole- cules.” Reproductive Biology and Endo- crinology : RB&E 8 (2010).
  13. Cheryl E. Dunlop & Richard A. An- derson ,”The regulation and assessment of follicular growth” .2014,,Pages 13- 17.
  14. Zeleznik AJ. The physiology of fol- licle selection. Reprod. Biol. Endocrinol. 2004;2:31.
  15. Branigan EF1, Estes A. Use of mi- cro-dose human chorionic gonadotropin (hCG) after clomiphene citrate (CC) to complete folliculogenesis in previous re- sistant anovulation. Am J Obstet Gyne- col. 2005 Jun;192(6):1890-6.
  16. Singh N., Bahadur A., Mittal S., Mal- hotra N., Bhatt A. Predictive value of en- dometrial thickness, pattern and subendo- metrial blood flows on the day of hCG by 2D Doppler in in-vitro fertilization cycles: a prospective clinical study from a tertiary care unit J Hum Reprod Sci, 4 (2011), 29 Iraqi Journal Of Embryos and Infertility Researches Vol.(8) Issue-1 (2018) 16. Hussein, Zainab; Al-Obaidi, Manal Taha; AL-Saadi, Wasan Ismail; Selman, Mohammad Oda.Comparison of the Ef- fect of Clomiphene citrate and Letro- zole on the Endometrial Parameters of PCOS Women Journal of Pharmaceu- tical Sciences and Research; Cuddalore . 2017;11(9): 2291-2295.
  17. Kupesic S., Bekavac I., Bjelos D., Kurjak A., Assessment of endometrial re- ceptivity by transvaginal color Doppler and three-dimensional power Doppler ultrasonography in patients undergoing in vitro fertilization procedures J Ultra- sound Med, 20 (2001), 125
  18. Chen S., Wu F., Luo C., Chen X., Shi X., Zheng H. , et al. Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertiliza- tion and embryo transfer: a retrospective cohort study Reprod Biol Endocrinol, 8 (2010), 30-36
  19. Filicori M, Cognigni GE, Gamberi- ni E, et al. Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation. Fertil Steril. 2005;84:394–401. [PubMed]
  20. Tesarik J., Hazout A., & Mendo- za C.Luteinizing hormone affects uter- ine receptivity independently of ovarian function. Reproductive Biomedicine On- line.2003;Vol.7, No. 1, pp. 59-64.
  21. Mahnaz Ashrafi,Kiandokht Kiani, Afsaneh Ghasemi, Fatemeh Rastegar ,Maryam Nabavi. The effect of low dose human chorionic gonadotropin on follic- ular response and oocyte maturation in PCOS patients undergoing IVF cycles: a randomized clinical trial of efficacy and safety. Springer-Verlag 2011.