{"paper_id":"f2efae7e-04d8-4e4e-bc5d-bde82ff9e79b","body_text":"Review began\n 12/24/2025 \nReview ended\n 01/10/2026 \nPublished\n 01/11/2026\n© Copyright \n2026\nDouraidi et al. This is an open access\narticle distributed under the terms of the\nCreative Commons Attribution License CC-\nBY 4.0., which permits unrestricted use,\ndistribution, and reproduction in any\nmedium, provided the original author and\nsource are credited.\nDOI:\n 10.7759/cureus.101281\nHeterotopic Pregnancy After Ovulation Induction\nby Clomiphene Citrate: A Case Report\nNada Douraidi \n, \nHassnaa Sarhane \n, \nFatima Zahra Belouaza \n, \nSoukaina Mouiman \n, \nAziz Baidada \n1.\n Gynecology-Obstetrics and Endoscopy Department, Maternity Souissi, University Hospital Center IBN SINA, Rabat,\nMAR\nCorresponding author: \nNada Douraidi, \nnadadouraidi49@gmail.com\nAbstract\nHeterotopic pregnancy (HP), when intrauterine and ectopic pregnancies occur together, is uncommon but\ndangerous. While rare in spontaneous conception, the risk increases with fertility treatments like\nclomiphene citrate (CC). These cases are easily missed because doctors may be reassured by the intrauterine\npregnancy and overlook the ectopic one. We describe a 31-year-old woman with primary infertility who\nconceived following clomiphene-induced ovulation. At seven weeks, she developed pelvic pain and vaginal\nbleeding. She was hemodynamically unstable with tachycardia and low blood pressure. Ultrasound showed\nan intrauterine sac alongside a left adnexal sac without fetal heartbeat, plus fluid in the pelvis indicating\nbleeding. We diagnosed HP and performed emergency laparotomy with left salpingectomy due to her\nunstable condition. She recovered well with first-trimester progesterone support and delivered vaginally at\n40 weeks without complications. This case highlights how challenging HP can be to diagnose. Even when an\nintrauterine pregnancy is visible, clinicians should consider HP in patients with pelvic pain and fertility\ntreatment history. Clomiphene increases this risk even without other predisposing factors. Ultrasound must\ninclude careful adnexal examination to avoid missing the diagnosis. Hemodynamically unstable patients\nneed immediate surgery to control bleeding and protect the intrauterine pregnancy. With timely recognition\nand proper management, including progesterone support, good outcomes are possible. Vigilance is essential\nfor all patients undergoing ovulation induction.\nCategories:\n Obstetrics/Gynecology\nKeywords:\n clomiphene citrate, heterotopic pregnancy (hp), ovulation induction, salpingotomy, ultrasonographic\ndiagnosis\nIntroduction\nHeterotopic pregnancy (HP) occurs when a woman carries both an intrauterine and an ectopic pregnancy at\nthe same time \n[1-2]\n. This is quite rare in natural pregnancies, happening in roughly one out of every 30,000\ncases \n[3-4]\n. However, as fertility treatments have become more common, we are seeing HP more frequently -\nnow affecting about one in 3,900 pregnancies among women using assisted reproductive technologies\n(ARTs) or ovulation-inducing medications \n[4-5]\n.\nWomen who develop HP typically share the same risk factors as those prone to ectopic pregnancies. A history\nof pelvic inflammatory disease, prior ectopic pregnancies, previous tubal surgeries, or pelvic adhesions all\nincrease vulnerability. Fertility medications like clomiphene citrate (CC) and gonadotropins can further\nelevate this risk, particularly when there's pre-existing damage to the fallopian tubes \n[6]\n.\nThe challenge with HP lies in catching it early. Once physicians identify an intrauterine pregnancy on\nultrasound, they often feel reassured and may not think to look for an additional ectopic pregnancy\nhappening simultaneously. While transvaginal ultrasound remains our primary diagnostic tool, it doesn't\nalways pick up HP in the early weeks, leading to missed diagnoses \n[7]\n. Unfortunately, this diagnostic delay\ncan result in dangerous complications, including ruptured tubes and significant internal hemorrhage.\nTreatment focuses on eliminating the ectopic pregnancy while safeguarding the healthy intrauterine one.\nSurgeons most commonly perform laparoscopic salpingectomy to achieve this \n[8]\n.\nWe report here a case of HP that developed after CC was used for ovulation induction. Our case underscores\nwhy clinicians must remain alert to the possibility of HP, especially when patients have undergone fertility\ntreatments.\nCase Presentation\nWe report the case of a 31-year-old woman, with no significant past medical history, married for five years\nwith no known consanguinity, and no history of contraception use. She presented with primary infertility of\nfive years’ duration.\n1\n1\n1\n1\n1\n \nOpen Access Case Report\nHow to cite this article\nDouraidi N, Sarhane H, Belouaza F, et al. (January 11, 2026) Heterotopic Pregnancy After Ovulation Induction by Clomiphene Citrate: A Case\nReport. Cureus 18(1): e101281. \nDOI 10.7759/cureus.101281\n\nThis was her first pregnancy (G1P0), estimated at seven weeks of gestation, achieved following ovulation\ninduction with CC.\nShe presented to the emergency department with a three-day history of left-sided pelvic pain, associated\nwith minimal dark vaginal bleeding.\nOn clinical examination, the patient showed signs of hemodynamic instability with tachycardia at 105 beats\nper minute and hypotension (blood pressure 90/60 mmHg). Abdominal examination revealed localized\ntenderness in the left iliac fossa.\nGynecological examination showed minimal dark bleeding originating from the endocervix.\nTransvaginal pelvic ultrasound revealed an anteverted, anteflexed uterus of increased size, with a thickened\nendometrium and the presence of an intrauterine gestational sac measuring 6 × 5 cm containing a yolk sac\nbut no visible embryo. In addition, a second gestational sac was identified in the left adnexal region,\ncontaining an embryo with a crown-rump length (CRL) corresponding to seven weeks and six days of\ngestation, but with no detectable cardiac activity. Signs of rupture were present, including a small amount of\nfree fluid in the pouch of Douglas (Figure \n1\n).\nFIGURE\n 1: Transvaginal ultrasonography showing heterotopic\npregnancy at seven weeks + six days\nA diagnosis of HP was made. Given the patient’s hemodynamic instability with tachycardia and hypotension,\nimmediate surgical intervention was required. After careful counseling and obtaining written informed\nconsent, an emergency laparotomy with left salpingectomy was performed rather than laparoscopy due to\nthe hemodynamic compromise (Figure \n2\n). During surgery, a hemoperitoneum of 50 mL was found and\nevacuated. Both ovaries were found to be normal.\n \n2026 Douraidi et al. Cureus 18(1): e101281. DOI 10.7759/cureus.101281\n2\n of \n5\n\nFIGURE\n 2: Intraoperative view of a left-sided tubal ectopic pregnancy\ncoexisting with an intrauterine gestation.\nPostoperative recovery was uneventful. The patient was discharged on postoperative day 3 in stable\ncondition. Throughout the first trimester, she received progesterone supplementation to support the\nintrauterine pregnancy. Regular antenatal follow-up was maintained, and the pregnancy progressed\nnormally without complications. At 40 weeks and three days of gestation, she delivered vaginally a healthy\nnewborn weighing 3,200 grams with Apgar scores of 9 and 10 at one and five minutes, respectively. Both\nmother and baby had an uncomplicated postpartum course.\nDiscussion\nWhen both an intrauterine and ectopic pregnancy develop at the same time, we call this HP, a relatively\nuncommon occurrence. Natural conception sees this combination happen once in approximately 30,000\npregnancies. However, fertility treatments change these odds considerably: in vitro fertilization increases\nthe rate to about one in 100, while CC brings it to roughly one in 900 \n[9]\n.\nThe connection between CC and multiple pregnancies has been recognized for decades. In fact, Payne's team\nfirst reported a heterotopic case following clomiphene treatment in 1971. Since clomiphene became a\nfrontline option for helping women ovulate, physicians have documented numerous similar occurrences \n[10-\n13]\n.\nWhat makes ovulation induction particularly relevant here? The process itself may contribute to the\nproblem beyond typical ectopic risk factors. Clomiphene triggers elevated estrogen production, which can\n \n2026 Douraidi et al. Cureus 18(1): e101281. DOI 10.7759/cureus.101281\n3\n of \n5\n\ninterfere with normal egg transport timing through the fallopian tubes. When an egg moves more slowly\nthan usual, fertilization might occur before it reaches the uterus, setting the stage for tubal implantation.\nIdentifying HP presents real clinical challenges. The symptoms do not necessarily stand out; they can mirror\neither uncomplicated pregnancy or isolated ectopic pregnancy. Here is the problem: seeing a gestational sac\nin the uterus tends to put clinicians at ease, sometimes causing diagnostic delays. Consider this data point\namong 139 documented HP cases, ultrasound identified only 80 before surgery; the other 59 went\nunrecognized until doctors were already operating \n[14]\n. Complicating matters further, HP can easily be\nmistaken for conditions like a bleeding corpus luteum alongside normal pregnancy, or ovarian\nhyperstimulation syndrome.\nWhile transvaginal ultrasound serves as our primary diagnostic method, its detection rate for HP sits at just\n33% \n[15]\n. Given this limitation, the National Guideline Alliance advises that examining the adnexal regions\nshould be standard practice during all first-trimester scans \n[16]\n. Skipping this step can mean missing HP\nuntil serious complications develop, such as internal hemorrhage from a ruptured tube.\nTreatment strategies vary based on the patient's condition \n[17]\n. For stable, symptom-free women, careful\nobservation might be appropriate, though rupture remains a concern requiring vigilant ultrasound follow-up\n[18]\n. Surgical intervention-whether minimally invasive or open-becomes imperative when patients are\nunstable or rupture seems likely. Our patient presented with cardiovascular instability, including elevated\nheart rate and low blood pressure, which led us to choose open surgery over laparoscopy for faster\nhemorrhage control. Depending on the ectopic location, surgeons might remove the entire affected tube or\nperform a more conservative procedure to extract only the pregnancy tissue. First-trimester progesterone\ntherapy may benefit the continuing intrauterine gestation after removing the ectopic component. As our\nexperience illustrates, combining appropriate surgical technique with hormone supplementation can result\nin successful full-term delivery \n[19]\n. An alternative approach uses ultrasound-guided needle aspiration of the\nectopic gestational sac, potentially combined with non-teratogenic agents (methotrexate is contraindicated\nbecause it causes birth defects). This less invasive method only applies when visualization is excellent and\nhemodynamic parameters remain normal \n[19]\n. The bottom line: treatment must be tailored to each patient,\nand collaborative care among specialists consistently produces superior outcomes.\nConclusions\nWhile HP does not happen often, it creates real difficulties for clinicians trying to diagnose and manage it\nespecially when fertility treatments are involved. Our case highlights an important lesson: doctors cannot\nlet their guard down just because they have spotted a pregnancy in the uterus. The presence of an\nintrauterine gestation should not provide false comfort.\nUltrasound through the vaginal approach continues to be our most valuable diagnostic tool, but here is the\ncatch, it only works well when doctors carefully and methodically check the areas around the ovaries and\ntubes. What is particularly noteworthy is that HP can develop even in women who do not fit the typical risk\nprofile, particularly after using medications like CC to stimulate ovulation.\nThe key takeaway? Catching this condition quickly and correctly can make all the difference. Missing the\ndiagnosis can lead to dangerous complications, while identifying it promptly gives us the best shot at\nprotecting the healthy pregnancy developing in the uterus\nAdditional Information\nAuthor Contributions\nAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of the\nwork.\nConcept and design:\n  \nNada Douraidi, Hassnaa Sarhane, Fatima Zahra Belouaza, Aziz Baidada\nDrafting of the manuscript:\n  \nNada Douraidi, Hassnaa Sarhane, Soukaina Mouiman, Aziz Baidada\nCritical review of the manuscript for important intellectual content:\n  \nFatima Zahra Belouaza\nAcquisition, analysis, or interpretation of data:\n  \nSoukaina Mouiman\nSupervision:\n  \nSoukaina Mouiman, Aziz Baidada\nDisclosures\nHuman subjects:\n Informed consent for treatment and open access publication was obtained or waived by all\nparticipants in this study. \nConflicts of interest:\n In compliance with the ICMJE uniform disclosure form, all\n \n2026 Douraidi et al. Cureus 18(1): e101281. DOI 10.7759/cureus.101281\n4\n of \n5\n\nauthors declare the following: \nPayment/services info:\n All authors have declared that no financial support\nwas received from any organization for the submitted work. \nFinancial relationships:\n All authors have\ndeclared that they have no financial relationships at present or within the previous three years with any\norganizations that might have an interest in the submitted work. \nOther relationships:\n All authors have\ndeclared that there are no other relationships or activities that could appear to have influenced the\nsubmitted work.\nReferences\n1\n. \nGhulmiyyah LM, Eid J, Nassar AH, Mirza FG, Nassif J: \nRecurrent twin pregnancy, with the second a\nheterotopic pregnancy, following clomiphene citrate stimulation: an unusual case and a review of the\nliterature\n. Surg Technol Int. 2014, 25:195-200.\n2\n. \nReece EA, Petrie RH, Sirmans MF, Finster M, Todd WD: \nCombined intrauterine and extrauterine gestations:\na review\n. Am J Obstet Gynecol. 1983, 146:323-30. \n10.1016/0002-9378(83)90755-x\n3\n. \nFranke C, Röhrborn A, Thiele H, Glatz J: \nCombined intrauterine and extrauterine gestation. A rare cause of\nacute abdominal pain\n. Arch Gynecol Obstet. 2001, 265:51-2. \n10.1007/s004040000120\n4\n. \nTalbot K, Simpson R, Price N, Jackson SR: \nHeterotopic pregnancy\n. J Obstet Gynaecol. 2011, 31:7-12.\n10.3109/01443615.2010.522749\n5\n. \nPerkins KM, Boulet SL, Kissin DM, Jamieson DJ: \nRisk of ectopic pregnancy associated with assisted\nreproductive technology in the United States, 2001-2011\n. Obstet Gynecol. 2015, 125:70-8.\n10.1097/AOG.0000000000000584\n6\n. \nJeon JH, Hwang YI, Shin IH, Park CW, Yang KM, Kim HO: \nThe risk factors and pregnancy outcomes of 48\ncases of heterotopic pregnancy from a single center\n. J Korean Med Sci. 2016, 31:1094-9.\n10.3346/jkms.2016.31.7.1094\n7\n. \nLi XH, Ouyang Y, Lu GX: \nValue of transvaginal sonography in diagnosing heterotopic pregnancy after in-\nvitro fertilization with embryo transfer\n. Ultrasound Obstet Gynecol. 2013, 41:563-9. \n10.1002/uog.12341\n8\n. \nVaishnav V: \nA very rare case of heterotopic pregnancy in natural conception with ectopic pregnancy as\npartial mole!\n. J Obstet Gynaecol India. 2014, 64:433-5. \n10.1007/s13224-013-0426-y\n9\n. \nOuafidi B, Kiram H, Benaguida H, Lamrissi A, Fichtali K, Bouhya S: \nDiagnosis and management of a\nspontaneous heterotopic pregnancy: rare case report\n. Int J Surg Case Rep. 2021, 84:106184.\n10.1016/j.ijscr.2021.106184\n10\n. \nTal J, Haddad S, Gordon N, Timor-Tritsch I: \nHeterotopic pregnancy after ovulation induction and assisted\nreproductive technologies: a literature review from 1971 to 1993\n. Fertil Steril. 1996, 66:1-12. \n10.1016/s0015-\n0282(16)58378-2\n11\n. \nAlqahtani HA: \nA case of heterotopic pregnancy after clomiphene-induced ovulation\n. SAGE Open Med Case\nRep. 2019, 7:2050313X19873794. \n10.1177/2050313X19873794\n12\n. \nMorong JJ, Janssen J, Morgan JC, Rodriguez SM: \nHeterotopic triplet pregnancy after clomiphene citrate\n.\nOchsner J. 2021, 21:416-8. \n10.31486/toj.20.0150\n13\n. \nNaki MM, Tekcan C, Uysal A, Güzin K, Yücel N: \nHeterotopic pregnancy following ovulation induction by\nclomiphene citrate and timed intercourse: a case report\n. Arch Gynecol Obstet. 2006, 274:181-3.\n10.1007/s00404-006-0121-7\n14\n. \nSoares C, Maçães A, Novais Veiga M, Osório M: \nEarly diagnosis of spontaneous heterotopic pregnancy\nsuccessfully treated with laparoscopic surgery\n. BMJ Case Rep. 2020, 13:\n10.1136/bcr-2020-239423\n15\n. \nWebster K, Eadon H, Fishburn S, Kumar G: \nEctopic pregnancy and miscarriage: diagnosis and initial\nmanagement: summary of updated NICE guidance\n. BMJ. 2019, 367:l6283. \n10.1136/bmj.l6283\n16\n. \nLi JB, Kong LZ, Yang JB, Niu G, Fan L, Huang JZ, Chen SQ: \nManagement of heterotopic pregnancy:\nexperience from 1 tertiary medical center\n. Medicine (Baltimore). 2016, 95:e2570.\n10.1097/MD.0000000000002570\n17\n. \nSentilhes L, Bouet PE, Gromez A, Poilblanc M, Lefebvre-Lacoeuille C, Descamps P: \nSuccessful expectant\nmanagement for a cornual heterotopic pregnancy\n. Fertil Steril. 2009, 91:934.e11-3.\n10.1016/j.fertnstert.2008.09.072\n18\n. \nEom JM, Choi JS, Ko JH, Lee JH, Park SH, Hong JH, Hur CY: \nSurgical and obstetric outcomes of laparoscopic\nmanagement for women with heterotopic pregnancy\n. J Obstet Gynaecol Res. 2013, 39:1580-6.\n10.1111/jog.12106\n19\n. \nGoldstein JS, Ratts VS, Philpott T, Dahan MH: \nRisk of surgery after use of potassium chloride for treatment\nof tubal heterotopic pregnancy\n. Obstet Gynecol. 2006, 107:506-8. \n10.1097/01.AOG.0000175145.23512.5e\n \n2026 Douraidi et al. Cureus 18(1): e101281. DOI 10.7759/cureus.101281\n5\n of \n5","source_license":"CC0","license_restricted":false}