{"paper_id":"3143d2f5-10ea-48d7-bb22-f436974c1509","body_text":"~ 10 ~ \nInternational Journal of Clinical Obstetrics and Gynaecology 2020; 4(6): 10-12 \n \nISSN (P): 2522-6614 \nISSN (E): 2522-6622 \n© Gynaecology Journal \nwww.gynaecologyjournal.com  \n2020; 4(6): 10-12 \nReceived: 10-09-2020 \nAccepted: 16-10-2020 \n \nDr. Neha G Jagdale  \nMBBS, MS, OBGY, Department of \nReproductive Medicine and \nResearch, Nowrosjee Wadia \nMaternity Hospital, Parel Mumbai, \nMaharashtra, India \n \nDr. Sukhpreet D Patel \nMBBS, MD, DNB, FCPS, DGO, \nPGDMLS, Department of \nReproductive Medicine and \nResearch, Nowrosjee Wadia, \nMaternity Hospital, Parel Mumbai, \nMaharashtra, India \n \nDr. Priyanka H Vora  \nMBBS, DGO, FCPS, DFP, BIMIE, \nDepartment of Reproductive \nMedicine and Research, Nowrosjee \nWadia Maternity Hospital, Parel \nMumbai, Maharashtra, India  \n \nDr. Mehernosh J Jassawalla \nMBBS, MD, FCPS, DGO, DFP, \nFICOG, FICMCH, FIAJAGO, \nFICA(US), FRSH (ENG), \nDepartment of Reproductive \nMedicine and Research, Nowrosjee \nWadia Maternity Hospital, Parel \nMumbai, Maharashtra, India \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nCorresponding Author: \nDr. Neha G Jagdale  \nMBBS, MS, OBGY, Department of \nReproductive Medicine and \nResearch, Nowrosjee Wadia \nMaternity Hospital, Parel Mumbai, \nMaharashtra, India \n \nNovel use of dienogest prior to embryo transfer in \npatient with multiple fibroids \n \nDr. Neha G Jagdale, Dr. Sukhpreet D Patel , Dr. Priyanka H Vora and Dr. \nMehernosh J Jassawalla \n \nDOI: https://doi.org/10.33545/gynae.2020.v4.i6a.724  \n \nAbstract \nUterine leiomyomas are the most common benign tumors amongst women of the reproductive age group \nwith the potential of affecting their fertility. In the subset of cases where fibroids are inoperable, there is a \nneed f or medical improvisation. Dienogest is one such well studied progestin used for the treatment of \nendometriosis. In our case report, we would like to highlight the novel use of pre -Assisted Reproduction \nTechnology (ART) dienogest in a patient with multiple fibroids, frozen pelvis and desirous of conception. \n \nKeywords: Uterine fibroids, dienogest, infertility, frozen pelvis \n \n1. Introduction  \nWhile it has been reported that fibroids affect approximately 5 -10% of the infertile population, \nthey may be responsibl e for infertility in only 1 -2.4% of these patients [1]. Amongst multiple \npathways, their impact on fertility is probably due to the alteration of endometrial receptivity \nleading to defective implantation [2]. Therefore, management of fibroids before embryo  transfer \nis crucial in such patients.  The increased morbidity, complications and costs of fibroid surgery \ncreates the  need for medical management, especially in cases that are inoperable such as in \nfrozen pelvis. Dienogest is one such novel option that we would like to present. \n \n2. Case report \nA 28 year old female married for nine years was referred to our center with secondary infertility. \nShe had a spontaneous pregnancy six years post marriage which resulted in a missed abortion at \n6 weeks of gestation. She had already undergone two laparoscopic ovarian cystectomies for \nbilateral large endometriotic cysts, which were confirmed on histopathology. Following this, she \nunderwent another laparoscopy for endometriosis associated pain, during which she was \ndiagnosed as frozen pelvis. These procedures were performed at another center prior to referral \nto our hospital. Fertility work up of the couple revealed normal results except for the low anti \nmullerian hormone level of the patient which was  0.29 ng/dl. Her ultrasound revealed a 2.3cm X \n3cm left hydrosalpinx and a uterus studded with multiple intramural and submucosal fibroids \nranging from 4 to 30 mm. It also revealed bilateral small endometriotic cysts ranging from 10 -25 \nmm [Fig 1] and an endometrial thickness of 7.5 mm (type 2 with zone 1 Applebaum staging). In \nview of her diminished ovarian reserve, the couple was counselled regarding the use of donor \noocytes. Despite her previous surgeries and difficult laparoscopic access to the fibroids, a \nhysteroscopic myo mectomy with delinking of the hydrosalpinx was performed to optimize her \ntreatment. Following endoscopy, the fibroids were suppressed with 3 months of leuprolide \ndepot. Unfortunately, she followed up after a gap of six months,  during which the fibroids had  \nenlarged once again. In order to avoid the long term side effects of Gonadotropin Releasing \nHormone agonist (GnRha) combined with the advantage of the antiestrogenic dienogest effect  \non fibroid volume reduction, we decided to start her on 2mg daily for th ree months of the oral \npreparation. Her subsequent scan at the end of this period revealed a significant reduction in the \nsize of the fibroids with endometrial Doppler zone 3 on Applebaum staging. Her endometrial \ncycle preparation for embryo transfer was d one with letrozole and she conceived in her first \nattempt and delivered a 2.4 kg female child by elective caesarean at 37.4 weeks of gestation with \nan apgar score of 9/10. \n \n\n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 11 ~ \n \n \nFig 1: Uterine cavity in the sagittal view showing multiple intramural and submucosal fibroids. \n \n3. Discussion \nFibroids and endometriosis often coexist due to their \ndependence on estrogen [3]. Fibroids negatively affect fertility \nand implantation rate by multiple mechanisms [Table 1] [1, 4, 5] \nFurther, fibroids larger than 4cm or those distorting the \nendometrium can potentially hinder implantation. Also based on \ntheir anatomical location, submucous, intramural and subserosal \nfibroids are the causative agents of infertility in decreasing \norder. Accurate fibroid mapping by an expert sonologist using \nultrasound is a critical step in such an assessment [1, 5]. \n \nTable 1: Pathophysiology of fibroids on fertility \n \n \n \nWomen with fibroids who desire future fertility face a dilemma \nbecause of the limited treatment choices. The conventional  \nmethods used for management of symptomatic fibroids are \nsurgical (which was not possible in our case), uterine artery \nembolisation (our patient was not willing to undergo any further \noperative intervention) and GnRH agonists (which were already \nused over a period of three months, post which the patient was \nlost to follow up). Dienogest is a 19 -nortestosterone derivative \nbelonging to the estrane group having antigonadotropic effects, \nwith limited androgenic, glucocorticoid and mineralocorticoid \nactivity [6]. Its mechanism for fibroid size reduction is shown in \nTable 2 \nDienogest is used as monotherapy at an oral dose of 2 mg once \ndaily for 3 months. It has a high oral bioavailability (90%) with \nfast renal elimination of metabolites (10 hours). It is indicate d in \nwomen who require temporary reduction in myoma volume, \nwhere surgical intervention is not possible. Ichigo S et al. over a \n24 month period, compared the effect of dienogest with that of \nGnRH agonist on the size of fibroids in women with coexisting \nendometriosis. They observed a comparable myoma size \nreduction in both groups but with significant side effects of \nGnRHa [6]. Hence, our approach utilised the estrogen \nsuppression advantage of dienogest over adverse effects of \nprolonged use of GnRHa. Thus die nogest can be used as an \nalternative mode of medical management of fibroids in the \nfertility seeking population. However, we currently lack  \nevidence from prospective randomized studies that can support \nthis hypothesis.  \n \n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 12 ~ \nTable 2: Mode of Action of Dienogest \n \n \n \n4. Conclusion \nIn cases where fibroids are inoperable, medical management \nwith dienogest can go a long way in improving endometrial \nreceptivity and improving success rates especially in a \npopulation anxious to conceive.  Also, surgical complications \nand long term consequences of GnRHa can be avoided by the \nappropriate use of dienogest. \n \n5. References \n1. Donnez J, Jadoul P. What are the implications of myomas \non fertility? A need for a debate? J of Hum Reprod \n2002;17:1424-30. DOI: 10.1093/humrep/17.6.1424 \n2. Rackow B, Taylor H. Submucosal uterine leiomyomas have \na global effect on molecular determinants of endometrial \nreceptivity. J of Fertil Steril  2010;93:2027-34. doi: \n10.1016/j.fertnstert.2008.03.029 \n3. Huang J, Lathi R, Lemyre M, Rodriguez H et al . \nCoexistence of endometriosis in women with symptomatic \nleiomyomas. J of Fertil Steril 2010;94:720 -723. DOI:  \n10.1016/j.fertnstert.2009.03.052 \n4. Essam El Mahdi  Fibroids and Infertility EMJ Repro Health \n2019;5(1):94-99.  \n5. Purohit P, Vigneswaran K. Fibroids and infertilit y. Curr \nObstet Gynecol  Rep 2016;5:81 -88. DOI: 10.1007/s13669-\n016-0162-2 \n6. Ichigo S, Takagi H, Matsunami K et al. Beneficial effects of \ndienogest on uterine myoma volume: a retrospective \ncontrolled study comparing gonadotropin -releasing \nhormone agonist. Arch Gynecol Obstet 2011 ;284:667-670. \nDOI: 10.1007/s00404-010-1732-6","source_license":"CC0","license_restricted":false}