The effect of a natural vaginal product based on honey on the success of intrauterine insemination (IUI) in infertility treatment

Document Type : Original Research Article


1 Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Traditional Medicine, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

6 Department of pharmaceutical sciences in Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.


Objective: Due to high prevalence of infertility and increasing tendency towards complementary medicine, this study was conducted to investigate the effect of a vaginal natural product based on honey and 1% extract of Myristica fragrans on the extent of success of intrauterine insemination (IUI).
Materials and Methods: This non-randomized clinical trial study with a historic control group, was performed on infertile women. In this trial, 159 patients were assigned to the intervention group, and 288 patients were recruited to the control group. All the participants received clomiphene or letrozole from the third up to seventh day of menstruation, and on days 6, 7, and 8, they received human menopausal gonadotrophin (HMG) injections. IUI was performed 36 hours after human chorionic gonadotrophin (HCG) injection. In the intervention group, a natural vaginal product was used besides the above treatments, from menstruation day 7 until the day before performing IUI. Sixteen days after IUI, serum beta HCG was measured to investigate chemical pregnancy, and six weeks following IUI, vaginal sonography was performed to investigate clinical pregnancy.
Results: Analysis showed that the pregnancy rate was higher in the group that receiving the natural product compared to the control group. Chemical pregnancy rate was 18.1% vs. 15.4%, and clinical pregnancy rate was 15.2% vs. 13.8% for intervention and control groups, respectively; but, this difference was not significant.
Conclusion: It seems that the use of this vaginal product for a longer period of time and across several menses cycles before IUI, may produce more positive results. Further studies, however, are needed to be done. 


Main Subjects

Abdelhafiz AT, Muhamad JA. 2008. Midcycle pericoital intravaginal bee honey and royal jelly for male factor infertility. Int J Gynaecol Obstet, 101: 146-149.
Abdelkader AM, Yeh J. 2009. The potential use of intrauterine insemination as a basic option for infertility: a review for technology-limited medical settings. Obstet Gynecol Int, 2009: 584837.
Akhondi MM, Kamali K, Ranjbar F, Shirzad M, Shafeghati S, Behjati Ardakani Z, Goodjani A, Parsaeian M. 2013. Prevalence of Primary Infertility in Iran in 2010. Iran J Public Health, 42: 1398-1404.
Allahbadia, GN. 2017. Intrauterine Insemination: Fundamentals Revisited. J Obstet Gynaecol India, 67: 385-392.
Azamkhan, M. 2008. Exir Azam. Tehran, Institute of Medical History, pp. 704-753
Brudzynski K, Sjaarda C. 2015. Honey glycoproteins containing antimicrobial peptides, Jelleins of the Major Royal Jelly Protein 1, are responsible for the cell wall lytic and bactericidal activities of honey. PLoS One, 10: e0120238.
Cabry-Goubet R, Scheffler F, Belhadri-Mansouri N, Belloc S, Lourdel E, Devaux A, Chahine H, De Mouzon J, Copin H. 2017. Effect of gonadotropin types and indications on homologous intrauterine insemination success: A study from 1251 cycles and a review of the literature. Biomed Res Int, 2017: 3512784.
Campisciano G, Florian F, D'Eustacchio A, Stankovic D, Ricci G, De Seta F. 2017. Subclinical alteration of the cervical-vaginal microbiome in women with idiopathic infertility. J Cell Physiol, 232: 1681-1688.
Checker R, Chatterjee S, Sharma D, Gupta S, Variyar P, Sharma A. 2008. Immunomodulatory and radioprotective effects of lignans derived from fresh nutmeg mace (Myristica fragrans) in mammalian splenocytes. Int Imp, 8: 661-669.
Chiu S, Wang T, Belski M, Abourashed EA. 2016. HPLC-guided isolation, purification and characterization of phenylpropanoid and phenolic constituents of nutmeg kernel (Myristica fragrans). Nat Prod Commun, 11: 483-488.
El-Sheshtawy RI, El-Badry DA, Gamal A, El-Nattat WS, Almaaty AMA. 2016. Natural honey as a cryoprotectant to improve Arab stallion post-thawing sperm parameters. Asian Pac J Reprod, 5: 331-334.
 Eskew AM, Bedrick BS, Hardi A, Stoll CRT, Colditz GA, Tuuli MG. 2019. Letrozole compared with clomiphene citrate for unexplained infertility: A systematic review and meta-analysis. Obstet Gynecol, 3: 437-444
Fakhrildin MB, Alsaadi RA. 2014. Honey Supplementation to semen-freezing medium improveshuman sperm parameters post-thawing. J Family Reprod Health, 8: 27-31.
Ghahiri A, Mogharehabed N, Mamourian M. 2016. Letrozole as the first-line treatment of infertile women with poly cystic ovarian syndrome (PCOS) compared with clomiphene citrate: A clinical trial. Adv Biomed Res, 5: 6.
Grembecka M, Szefer P. 2013. Evaluation of honeys and bee products quality based on their mineral composition using multivariate techniques. Environ Monit Assess, 185: 4033-4047.
Grossi E, Castiglioni S, Moscheni C, Antonazzo P, Cetin I, Savasi VM. 2017. Serum magnesium and calcium levels in infertile women during a cycle of reproductive assistance. Magnes Res, 30: 35-41.
Hosseini A, Mollazadeh H, Amiri MS, Sadeghnia HR, Ghorbani 2017. Effects of a standardized extract of Rheum turkestanicum Janischew root on diabetic changes in the kidney, liver and heart of streptozotocin-induced diabetic rats. Biomed Pharmacother, 86: 605-611.
Irani M, Chow S, Keating D, Elder S, Rosenwaks Z, Palermo G. 2018. Optimizing the first-line fertility treatment. Gynecol Endocrinol, 20: 1-5.
Kazemijaliseh H, Ramezani Tehrani F, Behboudi-Gandevani S, Hosseinpanah F, Khalili D, Azizi F. 2015. The Prevalence and Causes of Primary Infertility in Iran: A Population-Based Study. Glob J Health Sci, 7: 226-232.
Lavaf M, Simbar M, Mojab F, Alavi Majd H, Samimi M. 2017. Comparison of honey and phenytoin (PHT) cream effects on intensity of pain and episiotomy wound healing in nulliparous women. J Complement Integr Med, 15: 28981445.
Mojahedi M, Naseri M, Majdzadeh R, Keshavarz M, Ebadini M, Nazem E. 2014. Reliability and validity assessment of mizaj questionnaire: A novel self-report scale in iranian traditional medicine. Iran Red Crescent Med J, 16: e15924.
Monraisin O, Chansel-Debordeaux L, Chiron A, Floret S, Cens S, Bourrinet S. 2016. Evaluation of intrauterine insemination practices: a 1-year prospective study in seven French assisted reproduction technology centers. Fertil Steril, 105: 1589-1593.
Moreno I, Codoner FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazan J. 2016. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol, 215: 684-703.
Moreno I, Franasiak JM. 2017. Endometrial microbiota-new player in town. Fertil Steril, 108: 32-39.
Pharmacopeia U. 2004. Bacterial endotoxin test. USP32/NF27: United States Pharmacopeia and National Formulary, 2004: 93-96.
Ranjbar AM, Sadeghpour O, Khanavi M, Shams Ardekani MR, Moloudian H, Hajimahmoodi M. 2015. Effects of the deslagging process on some physicochemical parameters of honey. Iran J Pharm Res, 14: 657-662.
Salim R, Ben-Shlomo I, Colodner R, Keness Y, Shalev E.  2002. Bacterial colonization of the uterine cervix and success rate in assisted reproduction: results of a prospective survey. Hum Reprod, 17: 337-340.
Seifi Nader Goli Z, Nahidi F, Safaeean AR, Javadzadeh Y, Eteraf Oskouee T.  2016. The effect of honey vaginal gel and clotrimazole vaginal cream on vaginal normal flour in women with vaginitis candidiasis. IJOGI, 19: 32-39.
Shahin AY, Ismail AM, Zahran KM, Makhlouf AM. 2008. Adding phytoestrogens to clomiphene induction in unexplained infertility patients--a randomized trial. Reprod Biomed Online 16: 580-588.
Shahin AY, Mohammed SA. 2014. Adding the phytoestrogen Cimicifugae Racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates - A randomized trial. Gynecol Endocrinol, 30: 505-510.
Sohrabvand F, Nazem E, Tansaz M, Keshavarz M, Hashem Dabaghian F, Nikbakht Nasrabady A, Ghooshehghir A, Bioos S, Mokaberinejad R. 2014. Investigation of the personal and uterine humor in infertile women referred to Vali-E-As hospital of Tehran, Iran in 2012. IJOGI, 17: 10-19.
Tajuddin, Ahmad S, Latif A, Qasmi IA. 2003. Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a comparative study. BMC Complement Altern Med, 3: 6.
Tajuddin, Ahmad S, Latif A, Qasmi IA, Amin KM. 2005. An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg). BMC Complement Altern Med, 5: 16.
USDA N. 2007. The PLANTS Database (http://plants. usda. gov, 6 August 2007). National Plant Data Center. Baton Rouge, 2007: 70874-74490.
Veltman-Verhulst SM, Hughes E, Ayeleke RO, Cohlen BJ. 2016. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev, 2: CD001838.
Zaid SS, Othman S, Kassim NM. 2014. Potential protective effect of Tualang honey on BPA-induced ovarian toxicity in prepubertal rat. BMC Complement Altern Med, 14: 509.
Zaid SS, Sulaiman SA, Sirajudeen KN, Othman NH. 2010. The effects of Tualang honey on female reproductive organs, tibia bone and hormonal profile in ovariectomised rats--animal model for menopause. BMC Complement Altern Med, 10: 82.
Zhang C, Qi X, Shi Y, Sun Y, Li S, Gao X. 2012. Estimation of trace elements in mace (Myristica fragrans Houtt) and their effect on uterine cervix cancer induced by methylcholanthrene. Biol Trace Elem Res, 149: 431-434.