ABSTRACT BACKGROUND: Chromosomal abnormalities (CAs) have been described in patients with secondary amenorrhea (SA). However, studies on this association are scarce. OBJECTIVES: To evaluate the frequency and types of CAs detected by karyotyping in patients with SA. DESIGN AND SETTING: This retrospective study was performed in a reference clinical genetic service in South Brazil. METHODS: Data were obtained from the medical records of patients with SA who were evaluated between 1975 and 2022. Fisher’s bicaudate exact test and Student’s t-test were used, and P < 0.05 was considered significant. RESULTS: Among 43 patients with SA, 14 (32.6%) had CAs, namely del (Xq) (n = 3), 45,X (n = 2), 46,X,r(X)/45,X (n = 2), 46,XX/45,X (n = 1), 46,X,i(q10)/45,X (n = 1), 47,XXX (n = 1), 46,XX/47,XXX (n = 1), 46,XX/47,XX,+mar (n = 1), 45,XX,trob(13;14)(q10;q10)/46,XXX,trob(13;14)(q10;q10) (n = 1), and 46,XX,t(2;21)(q23;q11.2) (n = 1). Additional findings were observed mostly among patients with CA compared with those without CA (P = 0.0021). No difference in the mean age was observed between the patients with SA with or without CAs (P = 0.268025). CONCLUSIONS: CAs are common among patients with SA, especially those with short stature and additional findings. They are predominantly structural, involve the X chromosome in a mosaic, and are compatible with the Turner syndrome. Patients with SA, even if isolated, may have CAs, particularly del (Xq) and triple X. BACKGROUND (CAs . (SA) However scarce OBJECTIVES SETTING Brazil METHODS 197 2022 Fishers Fisher s Students Student ttest t used 005 0 05 0.0 significant RESULTS 4 1 32.6% 326 32 6 (32.6% Xq (Xq n 3, 3 , 3) 45X 45 2, 2 2) 46,X,rX/45,X 46XrX45X XrXX 46,X,r /45,X 46 r 46XX45X XXX XX 1, 1) 46,X,iq10/45,X 46Xiq1045X XiqX 46,X,i q10 i q 47XXX 47 46XX47XXX XXXXX 46XX47XXmar XXXXmar mar 45,XX,trob1314q10q10/46,XXX,trob1314q10q10 45XXtrob1314q10q1046XXXtrob1314q10q10 XXtrobqqXXXtrobqq 45,XX,trob 13 /46,XXX,trob trob 45,XX,trob(13;14)(q10;q10)/46,XXX,trob(13;14)(q10;q10 46,XX,t221q23q11.2 46XXt221q23q112 XXtqq 46,XX,t 21 q23 q11.2 q11 46,XX,t(2;21)(q23;q11.2 1. 0.0021. 00021 0.0021 0021 0.0021) 0.268025. 0268025 0.268025 268025 0.268025) CONCLUSIONS structural mosaic syndrome isolated (SA 19 202 00 0. 32.6 (32.6 rX XrX 46Xr Xr iq10 iq Xiq 46Xi Xi q1 XXmar trob1314q10q10 45,XX,trob1314q10q10/46,XXX,trob1314q10q1 XXtrob XXXtrob 45XXtrob1314q10q1046XXXtrob1314q10q1 45XXtrob 46XXXtrob 45,XX,trob(13;14)(q10;q10)/46,XXX,trob(13;14)(q10;q1 t221q23q11 46,XX,t221q23q11. XXt 46XXt221q23q11 46XXt q2 q112 q11. 46,XX,t(2;21)(q23;q11. 0002 0.002 002 026802 0.26802 26802 20 32. (32. iq1 trobqq trob1314q10q1 45,XX,trob1314q10q10/46,XXX,trob1314q10q 45XXtrob1314q10q1046XXXtrob1314q10q 45,XX,trob(13;14)(q10;q10)/46,XXX,trob(13;14)(q10;q tqq t221q23q1 46,XX,t221q23q11 46XXt221q23q1 46,XX,t(2;21)(q23;q11 000 0.00 02680 0.2680 2680 (32 trob1314q10q t221q23q 46,XX,t221q23q1 46XXt221q23q 46,XX,t(2;21)(q23;q1 0268 0.268 268 (3 46,XX,t221q23q 46,XX,t(2;21)(q23;q 026 0.26 26 ( 02 0.2

RESUMO A istmocele ou nicho uterino é representada por uma descontinuidade miometrial ou um defeito anecoico triangular na parede uterina anterior, com a base se comunicando com a cavidade uterina no local de uma cicatriz anterior de cesárea. O defeito pode ser classificado como pequeno ou grande, dependendo da espessura da parede miometrial deficiente. Embora geralmente assintomático, seu principal sintoma é o sangramento uterino anormal ou pós-menstrual; a dor pélvica crônica também pode ocorrer. Infertilidade, placenta acreta ou prévia, deiscência de cicatriz, ruptura uterina e gravidez ectópica em cicatriz de cesárea prévia também podem aparecer como complicações dessa condição. Os fatores de risco para desenvolvimento da istmocele comprovados até o momento incluem útero retroverso e múltiplas cesarianas. No entanto, fatores como localização mais inferior de uma cesárea prévia, fechamento incompleto da histerotomia, aderências precoces na parede uterina e predisposição genética também podem contribuir para o desenvolvimento de um nicho. Como não existem critérios definitivos para o diagnóstico de uma istmocele, vários métodos de imagem podem ser usados para avaliar a integridade da parede uterina e, assim, diagnosticar uma istmocele. Entretanto, ultrassonografia transvaginal e sono-histerografia com infusão salina surgem como métodos específicos, sensíveis e custo-efetivos para o diagnóstico de istmocele. O tratamento inclui manejo clínico ou cirúrgico, dependendo do tamanho do defeito, da presença de sintomas, da presença de infertilidade secundária e de planos de gravidez. O manejo cirúrgico inclui abordagens minimamente invasivas como histeroscopia, laparoscopia ou transvaginal, de acordo com o tamanho do defeito.

SUMMARY An isthmocele, a cesarean scar defect or uterine niche, is any indentation representing myometrial discontinuity or a triangular anechoic defect in the anterior uterine wall, with the base communicating to the uterine cavity, at the site of a previous cesarean section scar. It can be classified as a small or large defect, depending on the wall thickness of the myometrial deficiency. Although usually asymptomatic, its primary symptom is abnormal or postmenstrual bleeding, and chronic pelvic pain may also occur. Infertility, placenta accrete or praevia, scar dehiscence, uterine rupture, and cesarean scar ectopic pregnancy may also appear as complications of this condition. The risk factors of isthmocele proven to date include retroflexed uterus and multiple cesarean sections. Nevertheless, factors such as a lower position of cesarean section, incomplete closure of the hysterotomy, early adhesions of the uterine wall and a genetic predisposition may also contribute to the development of a niche. As there are no definitive criteria for diagnosing an isthmocele, several imaging methods can be used to assess the integrity of the uterine wall and thus diagnose an isthmocele. However, transvaginal ultrasound and saline infusion sonohysterography emerge as specific, sensitive and cost-effective methods to diagnose isthmocele. The treatment includes clinical or surgical management, depending on the size of the defect, the presence of symptoms, the presence of secondary infertility and plans of childbearing. Surgical management includes minimally invasive approaches with sparing techniques such as hysteroscopic, laparoscopic or transvaginal procedures according to the defect size.