{"paper_id":"2198cfd8-29e6-480d-b39f-ffa2d2de4350","body_text":"American Journal of Medical Case Reports, 2017, Vol. 5, No. 1, 4-7 \nAvailable online at http://pubs.sciepub.com/ajmcr/5/1/2 \n©Science and Education Publishing \nDOI:10.12691/ajmcr-5-1-2 \nThe Full-Term Delivery of a Normal Female Infant by a \nWoman with a Levonorgestrel Intrauterine System in \nSitu and Identified as Having Uterine Adenomyosis: A \nCase Report \nZhou Liang, Mingru Yin, Ai Ai, Yun Wang, Qiuju Chen, Songguo Xue, Yanping Kuang* \nDepartment of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, \nPeople's Republic of China \n*Corresponding author: Kuangyanp@126.com \nAbstract  This study reports an IVF patient who had adenomyosis underwent 2 in vitro fertilization (IVF) cycles \nand 3 frozen embryo transfer (FET) cycles but all failed. Then a Levonorgestrel-releasing intrauterine system (LNG-\nIUS) was inserted into her uterine. When her next menstrual period did not occur, the patient performed a urinary \npregnancy test and it was positive. The pregnancy progressed normally and the delivery was uncomplicated. An \nelective Caesarean delivery was performed at 39 weeks gestation. The IUD was found in the placenta and the \npostpartum recovery was uneventful. This is the first report of a woman, who having been identified with uterine \nadenomyosis, delivered a normal female infant with an LNG-IUS in situ. This case report indicated that LNG-IUS \nmay play some roles in changing the uterine environment of adenomyosis. \nKeywords: Levonorgestrel-releasing intrauterine system, in vitro fertilization, adenomyosis \nCite This Article: Zhou Liang, Mingru Yin, Ai Ai, Yun Wang, Qiuju Chen, Songguo Xue, and Yanping \nKuang, “The Full-Term Delivery of a Normal Female Infant by a Woman with a Levonorgestrel Intrauterine \nSystem in Situ and Identified as Having Uterine Adenomyosis: A Case Report.” American Journal of Medical \nCase Reports, vol. 5, no. 1 (2017): 4-7. doi: 10.12691/ajmcr-5-1-2. \n1. Introduction \nUterine adenomyosis is a common gynecological \ndisorder, characterized by the presence of heterotopic \nendometrial glands and stroma in the myometrium, with \nadjacent smooth muscle hyperplasia [1]. Therapy in the \nform of a  levonorgestrel intrauterine system (LNG-IUS) \nmay be beneficial in women with adenomyosis who wish \nto conceive after treatment. We report on a patient with an \nLNG-IUS in situ and uterine adenomyosis who became \npregnant and delivered a normal female infant in 2016. \nInstitutional Review Board approval for publication of this \ncase report was requested and granted, and written \npermission from the patient was obtained. Written \ninformed consent was obtained from each of the patients \nenrolled. \n2. Case Report \nIn 2012, a 38-year-old woman, gravida 3, para 0, with \nsecondary infertility for six years, and dysmenorrhea and \nintermenstrual bleeding, was referred to our unit for in \nvitro fertilization (IVF) and embryo transfer. The patient’s \npast history included two artificial abortions and a \nspontaneous one. A hysterosalpingography revealed \npartially obstructed Fallopian tubes.  \nIn our unit, she underwent artificial insemination by her \nhusband for two cycles but the urinary pregnancy test was \nnegative. After that, she underwent 2 in vitro fertilization \n(IVF) cycles using and 3 frozen embryo transfer (FET) \ncycles between April 2012 and April 2015 but all failed. \nThe ovarian stimulation protocol was progesterone primed \novarian stimilation which was previously described [2-6]. \nDuring this period of time, she also underwent times of \nHysteroscopy and experienced 3 cancellation of embryo \ntransfer as the as endometrial thickness was not thick \nenough.  \n2.1. Levonorgestrel-releasing intrauterine \nsystem insertion \nA repeat ultrasound scan suggested the presence of \nadenomyosis. Confirmation of adenomyosis was then \nmade using magnetic resonance imaging (MRI), according \nto traditional radiological criteria [7]. As reported, therapy \nwith the LNG-IUS can be beneficial in women with \nadenomyosis who wish to conceive after treatment [8-12]. \nA Mirena® IUD was placed on 27th. August 2015. At the \ntime of the appointment, the patient was on day  24 of a \n30-day cycle and the urinary pregnancy test was negative. \nShe reported having had unprotected intercourse on day \n12. She had been warned about a potential pregnancy \ndespite the insertion of the IUD during the luteal phase but \n \n\n American Journal of Medical Case Reports 5 \nelected to proceed regardless. The IUD was inserted and a \ntransvaginal ultrasound was performed. The location of \nthe LNG-IUS was correct and a gestational sac was not \nobserved in the uterine cavity. When her next menstrual \nperiod did not occur, the patient performed a urinary \npregnancy test and it was positive. She requested a \nperinatal opinion. An ultrasound confirmed a single live \nembryo consistent with eight weeks and three days \ngestation, with the LNG-IUS in place in the  uterus and \npositioned inferolaterally to the gestational sac . The risks \ndiscussed with the patient included  those that are general  \nto a pregnancy with an IUD in situ and those that relate to \nembryonic exposure to the LNG.  \n \nFigure 1. Picture from the ultrasound showing the IUD in place. (45 days of gestation) \n \nFigure 2. Picture from the ultrasound showing the IUD in place. (14 weeks of gestation) \n \n\n6 American Journal of Medical Case Reports  \n3. Result \nThe pregnancy progressed normally and the delivery \nwas uncomplicated . An elective Caesarean delivery was \nperformed at 39 weeks gestation. A female infant \nweighing 3210g was born without congenital \nabnormalities. Masculinization or any other anomalies in \nthe infant were not found. The IUD was found in the \nplacenta and the postpartum recovery was uneventful. \nThis case showed that in our experience a healthy infant \nhas been delivered without any abnormality. \n4. Discussion \nThe LNG-IUS is a popular, cost-effective method of \ncontraception. Pregnancy with the levonorgestrel released \nvia the IUS is unusual.Recently, it has been used as a \nmethod with non-contraceptive benefits; including slight \nmenstrual bleeding, a decrease in the number of \ndysmenorrhea incidents, and reduced pain associated with \nadenomyosis. The majority of women with an intrauterine \npregnancy with an IUD in situ either elect termination of \nthe pregnancy or experience spontaneous miscarriage [7]. \nIf the pregnancy continues, there is an increased risk of \nchorioamnionitis, spontaneous abortion, and preterm \ndelivery [13]. Pregnancies conceived with an IUD in place \nare associated with adverse pregnancy outcomes. T he \ngreatest risk pertains to those  pregnancies in which the \nIUD was not removed. The manufacturer of the LNG IUS \n(Mirena®) and the World Health Organization recommend  \nthe removal of the IUD in desired intrauterine gestations \n[14]. Responses to a questionnaire received from 17 360 \nLNG IUS users were analyzed in a study on 64 \npregnancies with the LNG IUS in situ. Thirty-three of the \npregnancies were ectopic. The five-year cumulative \npregnancy rate per 100 users was 0.5 and the five-year \nPearl Index rate was 0.11 [15].Elsewhere, it was reported \nthat normal newborn infants (a girl and a boy ) were \ndelivered at full term despite the exposure of the mothers \nto the LNG-IUS, embedded in the omentum, during the \npregnancy [16,17]. In another study, it was reported that \ntwo normal infant girls were born after first-trimester \nexposure to the LNG-IUS. One of the LNG-IUSs was \nexpulsed spontaneously [7] and the other was retrieved \nafter eight weeks [18]. In other studies, a healthy female \nand a male infant were delivered at term with an IUS in \nsitu [19,20]. Two full-term infants, the gender of which \nwas not reported, were also born in this way in other \nresearch [15]. \nIn the present case, the patient had previously  \nundergone three unsuccessful FET cycles in our unit \nowing to repeated  implantation failure. Thereafter, she \nwas identified as having uterine adenomyosis by MRI \ndiagnosis. According to the case report, the LNG-IUS was \ninserted 11 days after ovulation. This confirmed that \nconception must have occurred prior to the insertion of the \nIUS and was not considered a failure of the LNG-IUS \nsystem. Suggestions in the literature that  adenomyosis \ninterferes with embryo implantation are well known . \nSome investigators attribute thrombophilia and an \nimmunological attack on the implanted embryo to be the \ncauses of implantation failure [21]. It was demonstrated in \none study in which endometrial biopsies featured that \nadenomyosis was associated with a prominent aggregation \nof macrophages within the superficial endometrial glands \nwhich potentially interfered with embryo implantation \n[22]. The accumulation of macrophages in the superficial \nendometrial glands may give rise to a n immune \nenvironment which is hostile to the  implanted embryos. \nMoreover, some cytokines, such as tumor necrosis factor -\nalpha and interleukin-1, secreted from the macrophages, \nreactive oxygen, and nitrogen species, are all potentially \ntoxic to embryos [23].  \nIn our case,  in view of the patient’s spontaneous  \nabortion and the failure of several embryos to successfully \nimplant, we speculated that uterine adenomyosis could be \nthe reason for these . This abovementioned studies prove \nour point . The patient was treated  with hysteroscopy \nowing to her medical history of abortion by curettage and \nendometrial thickness of ≤ 5 mm. Several cycles of FET \nwere cancelled for this reason . Our patient was diagnosed \nwith adenomyosis with endometrial lesions.  \nAlthough the pathophysiology of adenomyosis has not \nbeen clarified, it was shown in a recent study that the \naltered expression of the steroid receptor co-regulators \nmay play a role in its development. In addition, the LNG-\nIUS, which has been broadly applied to patients with \nadenomyosis in clinical practice, may impact on the \ndisease by adjusting the signal transduction pathways \nwhich are activated by the steroid hormones [24]. In our \ncase, the LNG-IUS was accidentally inserted 11 days after \novulation. The chances of a successful implantation  were \ngreatly enhanced by an improvement in the intrauterine \nenvironment, facilitated by the LNG -IUS. Meanwhile, the \nability of the patient to maintain a normal pregnancy in the \nfirst trimester demonstrated the efficacy of the  LNG-IUS \nin treating adenomyosis, while simultaneously preventing \nspontaneous abortion. The use of the LNG-IUS was also \nassociated with an improvement in the number and quality \nof endometrial lesions.  \nUsually, risks of prematurity, miscarriage, and \nintrauterine infection are associated with a n intrauterine \npregnancy with an LNG-IUS in situ. The risk of potential \nmasculinization of the female fetus is a n additional \ntheoretical concern with its use [25]. Nevertheless, this \npregnancy was important to our patient, who wished to see \nit to full term . The pregnancy continued to progress \nnormally and a healthy female infant was born.  \nPregnancy is rare occurrence when an LNG-IUS is in \nsitu. Nevertheless, women should be informed of this \npossibility before its insertion to avoid any potential risks. \nTo the best of our knowledge, this is the first report of a \nwoman, who having been identified with uterine \nadenomyosis, delivered a normal female infant with an \nLNG-IUS in situ.  \n5. Conclusion \nWe report on a patient with an LNG-IUS in situ and \nuterine adenomyosis who became pregnant and delivered \na normal female infant in 2016. A female infant was born \nwithout congenital abnormalities. Masculinization or any \nother anomalies in the infant were not found. The IUD \n \n\n American Journal of Medical Case Reports 7 \nwas found in the placenta and the postpartum recovery \nwas uneventful. To the best of our knowledge, this is the \nfirst report of a woman, who having been identified with \nuterine adenomyosis, delivered a normal female infant \nwith an LNG-IUS in situ. This case report demonstrates \nthat LNG-IUS plays an important role in the successful \nmedical treatment of adenomyosis. \nReferences \n[1] Campo, S., V. Campo, and G. Benagiano, Infertility and \nadenomyosis. Obstet Gynecol Int, 2012. 2012: p. 786132. \n[2] Kuang, Y., et al., Medroxyprogesterone acetate is an effective oral \nalternative for preventing premature luteinizing hormone surges \nin women undergoing controlled ovarian hyperstimulation for in \nvitro fertilization. Fertil Steril, 2015. 104(1): p. 62-70 e3. \n[3] Kuang, Y., et al., Double stimulations during the follicular and \nluteal phases of poor responders in IVF/ICSI programmes \n(Shanghai protocol). Reprod Biomed Online, 2014. 29(6): p. 684 -\n91. \n[4] Kuang, Y., et al., Luteal-phase ovarian stimulation is feasible for \nproducing competent oocytes in women undergoing in vitro \nfertilization/intracytoplasmic sperm injection treatment, with \noptimal pregnancy outcomes in frozen -thawed embryo transfer \ncycles. 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