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Published in: The Journal of Obstetrics and Gynecology of India 1/2016

01-02-2016 | Editorial

Oral Drugs for Unexplained Infertility

Author: Gautam N. Allahbadia

Published in: The Journal of Obstetrics and Gynecology of India | Issue 1/2016

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Abstract

Of the infertile couples unable to conceive without any identifiable cause, 30 % are defined as having unexplained infertility. Management depends on duration of infertility and age of female partner. The treatment of unexplained infertility is empirical, and many different regimens have been used. Among these are expectant management, ovarian stimulation with clomiphene citrate, gonadotropins and aromatase inhibitors, fallopian tube sperm perfusion, tubal flushing, intrauterine insemination, gamete intrafallopian transfer, and IVF. The first approach to treatment of unexplained infertility generally is the use of drugs that stimulate oocyte production. For over four decades, the first-line treatment for ovarian stimulation in unexplained infertility has been clomiphene citrate. Multiple reports suggest that aromatase inhibitors may be effective alternative agents for ovarian stimulation in couples with unexplained infertility. Their administration is reported to be associated with monofollicular development in most cases, which may result in enhanced fertility and a reduced risk of ovarian hyperstimulation and multiple births, as compared to current standard therapies such as gonadotropin and clomiphene. Despite world evidence to the contrary, letrozole has been banned for use for infertility management in India since 2011.
Literature
1.
go back to reference Ghesquiere SL, Castelain EG, Spiessens C, et al. Relationship between follicle number and (multiple) live birth rate after controlled ovarian hyperstimulation and intrauterine insemination. Am J Obstet Gynecol. 2007;197:589.e1–5.CrossRef Ghesquiere SL, Castelain EG, Spiessens C, et al. Relationship between follicle number and (multiple) live birth rate after controlled ovarian hyperstimulation and intrauterine insemination. Am J Obstet Gynecol. 2007;197:589.e1–5.CrossRef
2.
go back to reference Samani FG, Farzadi L, Nezami N, et al. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Arch Gynecol Obstet. 2009;280:201–5.CrossRefPubMed Samani FG, Farzadi L, Nezami N, et al. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Arch Gynecol Obstet. 2009;280:201–5.CrossRefPubMed
3.
go back to reference Fisch P, Casper RF, Brown SE, et al. Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin. Fertil Steril. 1989;51:828–33.PubMed Fisch P, Casper RF, Brown SE, et al. Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin. Fertil Steril. 1989;51:828–33.PubMed
4.
go back to reference Practice Committee of American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion. Fertil Steril. 2012;97:825–34.CrossRef Practice Committee of American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion. Fertil Steril. 2012;97:825–34.CrossRef
5.
go back to reference Reynolds MA, Schieve LA, Martin JA, et al. Trends in multiple births conceived using assisted reproductive technology, United States, 1997–2000. Pediatrics. 2003;111:1159–62.PubMed Reynolds MA, Schieve LA, Martin JA, et al. Trends in multiple births conceived using assisted reproductive technology, United States, 1997–2000. Pediatrics. 2003;111:1159–62.PubMed
6.
go back to reference Schieve LA, Devine O, Boyle CA, et al. Estimation of the contribution of non-assisted reproductive technology ovulation stimulation fertility treatments to US singleton and multiple births. Am J Epidemiol. 2009;170:1396–407.CrossRefPubMed Schieve LA, Devine O, Boyle CA, et al. Estimation of the contribution of non-assisted reproductive technology ovulation stimulation fertility treatments to US singleton and multiple births. Am J Epidemiol. 2009;170:1396–407.CrossRefPubMed
7.
go back to reference Cook JL, Geran L, Rotermann M. Multiple births associated with assisted human reproduction in Canada. J Obstet Gynaecol Can. 2011;33:609–16.PubMed Cook JL, Geran L, Rotermann M. Multiple births associated with assisted human reproduction in Canada. J Obstet Gynaecol Can. 2011;33:609–16.PubMed
8.
go back to reference Guzick DS, Carson SA, Coutifaris C, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. N Engl J Med. 1999;340:177–83.CrossRefPubMed Guzick DS, Carson SA, Coutifaris C, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. N Engl J Med. 1999;340:177–83.CrossRefPubMed
9.
go back to reference Kulkarni AD, Jamieson DJ, Jones HW Jr, et al. Fertility treatments and multiple births in the United States. N Engl J Med. 2013;369:2218–25.CrossRefPubMed Kulkarni AD, Jamieson DJ, Jones HW Jr, et al. Fertility treatments and multiple births in the United States. N Engl J Med. 2013;369:2218–25.CrossRefPubMed
10.
go back to reference Ibrahim MI, Moustafa RA, Abdel-Azeem AA. Letrozole versus clomiphene citrate for superovulation in Egyptian women with unexplained infertility: a randomized controlled trial. Arch Gynecol Obstet. 2012;286(6):1581–7. doi:10.1007/s00404-012-2478-0.CrossRefPubMed Ibrahim MI, Moustafa RA, Abdel-Azeem AA. Letrozole versus clomiphene citrate for superovulation in Egyptian women with unexplained infertility: a randomized controlled trial. Arch Gynecol Obstet. 2012;286(6):1581–7. doi:10.​1007/​s00404-012-2478-0.CrossRefPubMed
11.
go back to reference Liu A, Zheng C, Lang J, et al. Letrozole versus clomiphene citrate for unexplained infertility: a systematic review and meta-analysis. J Obstet Gynaecol Res. 2014;40(5):1205–16. doi:10.1111/jog.12393.CrossRefPubMed Liu A, Zheng C, Lang J, et al. Letrozole versus clomiphene citrate for unexplained infertility: a systematic review and meta-analysis. J Obstet Gynaecol Res. 2014;40(5):1205–16. doi:10.​1111/​jog.​12393.CrossRefPubMed
16.
go back to reference Chen DT, Wynia MK, Moloney RM, et al. Physician knowledge of the FDA-approved indications of commonly prescribed drugs: results of a national survey. Pharmacoepidemiol Drug Saf. 2009;18(11):1–7. doi:10.1002/pds.1825.CrossRef Chen DT, Wynia MK, Moloney RM, et al. Physician knowledge of the FDA-approved indications of commonly prescribed drugs: results of a national survey. Pharmacoepidemiol Drug Saf. 2009;18(11):1–7. doi:10.​1002/​pds.​1825.CrossRef
18.
go back to reference Mitwally MF, Casper RF. Potential of aromatase inhibitors for ovulation and superovulation induction in infertile women. Drugs. 2006;66(17):2149–60.CrossRefPubMed Mitwally MF, Casper RF. Potential of aromatase inhibitors for ovulation and superovulation induction in infertile women. Drugs. 2006;66(17):2149–60.CrossRefPubMed
19.
go back to reference Sakhavar N, Kaveh M, Sadegi K. The impact of letrozole versus clomiphene citrate on uterine blood flow in patients with unexplained infertility. J Family Reprod Health. 2014;8(1):1–5.PubMedCentralPubMed Sakhavar N, Kaveh M, Sadegi K. The impact of letrozole versus clomiphene citrate on uterine blood flow in patients with unexplained infertility. J Family Reprod Health. 2014;8(1):1–5.PubMedCentralPubMed
20.
go back to reference Chaudhury K, Chaudhury S, Khastgir G, et al. An effective alternative to only gonadotrophin for controlled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination: a clinical trial. J Indian Med Assoc. 2013;111(9):589–92, 594. Chaudhury K, Chaudhury S, Khastgir G, et al. An effective alternative to only gonadotrophin for controlled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination: a clinical trial. J Indian Med Assoc. 2013;111(9):589–92, 594.
21.
go back to reference Bayar U, Tanriverdi HA, Barut A, et al. Letrozole vs. clomiphene citrate in patients with ovulatory infertility. Fertil Steril. 2006;85(4):1045–8.CrossRefPubMed Bayar U, Tanriverdi HA, Barut A, et al. Letrozole vs. clomiphene citrate in patients with ovulatory infertility. Fertil Steril. 2006;85(4):1045–8.CrossRefPubMed
22.
23.
24.
go back to reference Shokeir TA. Tamoxifen citrate for women with unexplained infertility. Arch Gynecol Obstet. 2006;274(5):279–83.CrossRefPubMed Shokeir TA. Tamoxifen citrate for women with unexplained infertility. Arch Gynecol Obstet. 2006;274(5):279–83.CrossRefPubMed
25.
go back to reference Shahin AY, Ismail AM, Zahran KM, et al. Adding phytoestrogens to clomiphene induction in unexplained infertility patients—a randomized trial. Reprod Biomed. 2008;16(4):580–8.CrossRef Shahin AY, Ismail AM, Zahran KM, et al. Adding phytoestrogens to clomiphene induction in unexplained infertility patients—a randomized trial. Reprod Biomed. 2008;16(4):580–8.CrossRef
26.
go back to reference Leanza V, Coco L, Grasso F, et al. Ovulation induction with clomiphene citrate for infertile couple. Minerva Ginecol. 2014;66(3):309–12.PubMed Leanza V, Coco L, Grasso F, et al. Ovulation induction with clomiphene citrate for infertile couple. Minerva Ginecol. 2014;66(3):309–12.PubMed
27.
go back to reference Leanza V, Coco L, Grasso F, et al. Unexplained infertility and ovulatory induction with menopausal gonadotropins. Minerva Ginecol. 2014;66(3):303–7.PubMed Leanza V, Coco L, Grasso F, et al. Unexplained infertility and ovulatory induction with menopausal gonadotropins. Minerva Ginecol. 2014;66(3):303–7.PubMed
28.
go back to reference Goldman MB, Thornton KL, Ryley D, et al. A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T). Fertil Steril. 2014;101(6):1574-81.e1–2. doi:10.1016/j.fertnstert.2014.03.012. Goldman MB, Thornton KL, Ryley D, et al. A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T). Fertil Steril. 2014;101(6):1574-81.e1–2. doi:10.​1016/​j.​fertnstert.​2014.​03.​012.
29.
go back to reference Yapca OE, Delibas IB, Karaca I, et al. Time-limited hydrotubation combined with clomiphene citrate treatment for unexplained infertility. Clin Exp Obstet Gynecol. 2015;42(3):311–4.PubMed Yapca OE, Delibas IB, Karaca I, et al. Time-limited hydrotubation combined with clomiphene citrate treatment for unexplained infertility. Clin Exp Obstet Gynecol. 2015;42(3):311–4.PubMed
Metadata
Title
Oral Drugs for Unexplained Infertility
Author
Gautam N. Allahbadia
Publication date
01-02-2016
Publisher
Springer India
Published in
The Journal of Obstetrics and Gynecology of India / Issue 1/2016
Print ISSN: 0971-9202
Electronic ISSN: 0975-6434
DOI
https://doi.org/10.1007/s13224-015-0805-7

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