Medical abortion: teratogenic effects of misoprostolGynaecology Case Reports 323 Declaration of interest: Th
e authors report no confl icts of interest. Th e cies continued to term, resulting in three infants (14.3%) born with authors alone are responsible for the content and writing of the paper. congenital malformations (Barnett 1996). Nevertheless, in 1997, a study involving 86 pregnant women who References
had taken misoprostol, and a similar control group, showed that the Cucinella G , Granese R , Calagna G et al . 2011 . Parasitic myomas aft er laparo- use of misoprostol was not associated with an increase in congenital scopic surgery: an emerging complication in the use of morcellator? Descrip- defects in infants (Sch ü ler et al. 1997). tion of four cases. Fertility and Sterility 96 : e90 – e96 . However, in 1998, it was found that 17 of 42 children born Epstein JH , Nejat EJ , Tsai T . 2009 . Parasitic myomas aft er laparoscopic myomec- to women who had used misoprostol to medically abort had tomy: case report . Fertility and Sterility 91 : 932.e13 – e14 . malformations on their extremities, as well as anomalies in cranial Hill DJ , Maher PJ , Wood EC . 1997 . Lost surgical specimens . Journal of the Ameri- can Association of Gynecologic Laparoscopists 4 : 277 – 279 . nerves (Gonz á lez et al. 1998). Nezhat C , Kho K . 2010 . Iatrogenic myomas: new class of myomas? Journal of In 2000, a study found that 57 of 9,653 of infants who had been Minimally Invasive Gynecology 17 : 544 – 550 . exposed to misoprostol, had been born with malformations (Orioli Niroumand N , Tabrizi NM , Dabirashraﬁ H et al . 1994 . Th e fate of a myoma when and Castilla 2000). left intraabdominally: a case report . Journal of the American Association of In 2006, a study reported on 13 cases of children born aft er failed Gynecologic Laparoscopists 1 : S26 . abortions induced by misoprostol; of these, three (23%) were born Rajab KE , Aradi AN , Datta BN . 2000 . Postmenopausal leiomyomatosis perito- with severe physical malformations (Gary and Harrison 2006). nealis disseminata International Journal of Gynaecology and Obstetrics e majority of the aforementioned cases were compiled in a review published in 2006 (Da Silva Dal Pizzol et al. 2006), which Takeda A , Imoto S , Mori M et al . 2012 . Rapid growth of parasitic myoma in early pregnancy: previously undescribed manifestation of a rare disorder aft er lap- included 4,899 women that had used mifepristone and misoprostol to aroscopic-assisted myomectomy . European Journal of Obstetrics, Gynecology, induce a medical abortion and which were compared with a control and Reproductive Biology 162 : 117 – 118 . group of 5,742 women. It was found that of the infants born with mal-formations, the most frequently-occurring congenital malformations were those occurring in the extremities and the Moebius syndrome. Two years later (2008), another case of the Moebius syndrome in Medical abortion: Teratogenic eﬀ ects of
a newborn was reported, attributed to a failed abortion with both mifepristone and misoprostol (Bos-Th ompson et al. 2008). misoprostol
However, it is also important to mention that the number of infants born with congenital defects aft er a failed medical abortion is quite small, as the effi cacy of this method is around 95%; that is, only J. Aznar 1 & P. Navarro 2 5% of women who use these drugs to induce a medical abortion will fail in their attempt. Although approximately 80% of these ensuing 1 Institute of Life Sciences and 2 Faculty of Nursing, Catholic University pregnancies will result in a live birth (Gary and Harrison 2006), the of Valencia, Valencia, Spain relatively small number of 15 – 20% of these infants will be born with congenital defects (Gary and Harrison 2006; Barnett 1996). DOI: 10.3109/01443615.2014.948405
Correspondence: Justo Aznar, Institute of Life Sciences, Catholic University of Conclusion
Valencia, C/Guillem de Castro 94, Valencia, 46003 Spain. E-mail: [email protected] e objective should be to prevent these malformations altogether, therefore many practitioners who perform abortions prefer surgical For personal use only.
abortions to medical abortions during early pregnancy, especially if Introduction
we consider the fact that the number of complications resulting from Some 40 million abortions are performed around the world every the surgical procedure is lower than those resulting from that using year. In Spain, this fi gure reached 112,390 in 2011. Of these, approxi- pharmacological agents. mately 5% were medical abortions. Th is percentage varies widely in In summary, medical abortion carries with it a number of potential other countries: 67% in Portugal; 49% in France; 40% in England; and teratogenic side-eff ects for infants resulting from failed abortions. We 70% in Scotland and Finland. believe this issue should be a part of any ethical discussion concern- In the 1980s, more than 20 clinical trials had proven the effi ing this type of procedure. of mifepristone coupled with misoprostol in inducing an abortion in the fi rst few weeks of pregnancy. Medical abortions however, cause Declaration of interest: Th
e authors report no confl icts of interest. negative side-eff ects, including teratogenic eff ects. e authors alone are responsible for the content and writing of the J Obstet Gynaecol Downloaded from informahealthcare.com by 18.104.22.168 on 04/30/15 Reported cases
e fi rst case of teratogenic eff ects associated with the use of mife- pristone was described in 1988, when Roger Henrion, Head of the References
maternity ward at Hospital Post-Royal of Paris, reported the case of an Barnett AA . 1996 . Mifepristone clears US regulatory hurdle . Lancet 348 : 256 . infant born with physical abnormalities aft er a failed abortion attempt ompson MA , Hillaise-Buys D , Roux C , Faille JL , Amram D . 2008 . M ö bius using RU-486 (Coles 1988). As far as we know, this is the only case of syndrome in a neonate aft er mifepristone and misoprostol elective abortion failure . Annals of Pharmacotherapy 42 : 888 – 892 . teratogenic alterations arising from the exclusive use of mifepristone. Coles P . 1988 . French government approves abortion pill for commercial use .
Other cases were described in 1991 (Fonseca et al. 1991). Five infants born to women that had taken misoprostol to induce a Da Silva Dal Pizzol T , Knop FF , Mengue SS . 2006 . Prenatal exposure to misopros- medical abortion showed an unusual congenital malformation in the tol and congenital anomalies: systematic review and meta-analysis . Reproduc- bones located in the frontal area of the cranium. A later case reported tive Toxicology 22 : 666 – 671 . by Fonseca et al. (1991) describes in greater detail, three of the cases Fonseca W , Alencar AJ , Mota FS , Coelho HL . 1991 . Misoprostol and congenital previously mentioned in the news section of the Lancet . malformations . Lancet 338 : 56 . In 1993, an article was published which provides an account of Gary MM , Harrison DJ . 2006 . Analysis of severe adverse events related to the use seven children born with malformations in their limbs, four of which of mifepristone as an abortifacient . Annals of Pharmacotherapy 40 : 191 – 197 . Genest DR , Richardson A , Rosenblatt M , Holmes L . 1994 . Limb defects and had been diagnosed with Moebius syndrome (Gonz á lez et al. 1993). omphalocele in a 17 week fetus following ﬁ rst trimester misoprostol exposure .
In 1994 Genest et al. (1994) reported on a failed abortion that was Teratology 49 : 418 . induced with misoprostol; the infant was born with deformed legs Gonz á lez CH , Marques-Dias MJ , Kim CA , Sugaryama SM , Da Paz JA , Huson and omphalocele. SM et al . 1998 . Congenital abnormalities in Brazilian children associ- In 1996, two French studies involving 2,480 women who had ated with misoprostol misuse in ﬁ rst trimester of pregnancy . Lancet 351 : taken mifepristone and misoprostol found that of these, 21 pregnan- 1624 – 1627 . 324 Gynaecology Case Reports Gonz á lez CH , Vargas FR , Á lvarez-P é rez AB , Kim CA , Brunoni D , Marques- noma is not usually considered in the diff erential diagnosis. Here, we Dias MJ et al . 1993 . Limb deﬁ ciency with or without M ö bius sequence report two cases of transitional cell carcinoma of the fallopian tube, in seven Brazilian children associated with misoprostol use in the ﬁ rst which had atypical presentations: one with pyrexia of unknown ori- trimester of pregnancy American Journal of Medical Genetics gin and the other, a cervical malignancy. Orioli IM , Castilla EE . 2000 . Epidemiological assessment of misopros- tol teratogenicity . British Journal of Obstetrics and Gynaecology 107 : Case report 1
A 59-year-old postmenopausal woman presented with lower abdom- Sch ü ler L , Pastuszak A , Sanseverino MT , Orioli IM , Brunoni D , Koren G . inal pain and high-grade fever of 1-month duration. Ultrasound 1997 . Pregnancy outcome aft er abortion attempt with misoprostol . Tera- examination was normal, except for low-level echoes in the cavity, tology 55 : 36 . suggestive of pyometra. Cultures were sterile. She was given antibiot-ics and dilatation and drainage was done. Endometrium was atrophic on evaluation. She continued to have a fever and collection in the endometrial cavity. At 6 months aft er follow-up, she was suspected Primary fallopian tube transitional cell
to have a right ovarian mass (4.6 ⫻ 2.3 cm) with CA125; 12 IU/ml (normal ⬍ 35 IU/ml). On staging laparotomy, she was found to have carcinoma
a tumour in the right fallopian tube, with no other deposits. She underwent total hysterectomy with bilateral salpingo-oophorectomy, A. Keepanasseril 1 , R. Bagga 1 , S. C. Saha 1 , P. Dey 2 , S. Gainder 1 multiple peritoneal biopsies and infracolic omentectomy. Histopatho- logical examination revealed it to be a transitional cell carcinoma. Peritoneal biopsy revealed granulomatous infl ammation but no evi- Departments of 1 Obstetrics and Gynecology and 2 Cytology and dence of malignancy. She was diagnosed as FIGO stage I. As she con- Gynecologic Pathology, Postgraduate Institute of Medical education tinued to have fever and peritoneal biopsy showing granulomatous and Research (PGIMER), infl ammation, she was given anti-tubercular treatment. However, Chandigarh, India the fever did not respond to this and subsided only aft er initiating chemotherapy. She received six courses of adjuvant chemotherapy DOI: 10.3109/01443615.2014.952223
once every 3 weeks with carboplatin (AUC ⫽ 6) and paclitaxel Correspondence: R. Bagga, Department of Obstetrics and Gynecology, Post (175 mg/m 2 ). She is in remission at 18-months follow-up. Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 160012, India. E-mail: [email protected] Case report 2
A 55-year-old woman presented with a history of postmenopausal
bleeding and foul smelling vaginal discharge. She had undergone Carcinoma of the fallopian tube is one of the rarest gynaecological a mastectomy for infi ltrating ductal carcinoma and had received tumours accounting for only 0.18 – 1.6% of gynaecological malignan- postoperative radiotherapy and tamoxifen, 25 years previously. cies (Nordin 1994). Preoperative diagnosis of fallopian tube carci- Pap smear was infl ammatory. Endocervical tissue of the fractional cult, most signs and symptoms are non-characteristic. curettage was suggestive of cervical squamous cell carcinoma. Type e most frequent clinical symptom at presentation is included in II radical hysterectomy and bilateral salpingo-oophorectomy with the Latkzo 's triad, which comprises of vaginal discharge or bleeding, pelvic lymphadenectomy was performed. Intraoperatively, the uterus lower abdominal pain and pelvic mass (Piura and Rabinovich 2000). was found to be of normal size and mobile. Th e left fallopian tube For personal use only.
However, a correct preoperative diagnosis is achieved in fewer than revealed a grey – white circumscribed tumour fi lling the lumen of the 5% of cases and, in many cases, tubal carcinoma is an incidental fi nd- tube. Examination of the surgical specimen revealed two nodules ing during surgery for an unrelated condition (Alvarado-Cabrero in the endocervical area. Histopathological examination revealed a et al. 1999). Although pelvic mass or bloody discharge is one of the poorly-diff erentiated transitional cell carcinoma of the left fallopian common presenting symptoms (Ben-Hur et al. 1999), tubal carci- tube with metastatic involvement in the cervix; the lymph nodes were J Obstet Gynaecol Downloaded from informahealthcare.com by 22.214.171.124 on 04/30/15 Figure 1. Photomicrograph of the peritoneal biopsy showing multiple epithelioid cell granulomas (a) and transitional cell carcinoma of the fallopian tube showing ribbon of tumour cells (c);(b) shows the presence of metastasis in the cervix (H & E, ⫻ 200).
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