Pregnancy outcomes in women exposed to cancer chemotherapy

Danet, Chloé; Araujo, Mélanie; Bos-Thompson, Marie-Andrée; Portolan, Ghyslaine; Gautier, Sophie; Vanlemmens, Laurence; Bonenfant, Sophie; Jonville‐Béra, Annie‐Pierre; Cottin, Judith; Vial, Thierry; Bavoux, F; Montastruc, Jean‐Louis; Damase‐Michel, Christine; Bénevent, Justine; Bourgeois-Mondon, Isabelle; Lacroix, Isabelle

doi:10.1002/pds.4689

Cited by 12 publications

(7 citation statements)

References 23 publications

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“…9 However, we have some recent studies including one from oncology where outcomes seem slightly better than previously noted. [10][11][12][13][14][15] and we are actively exploring and using modalities to preserve fertility. This includes embryo/ oocyte cryopreservation or ovarian tissue cryopreservation.…”

Section: Introductionmentioning

confidence: 99%

Pregnancy in patients with systemic lupus erythematosus after cyclophosphamide therapy

Sen

Kurl

Khosroshahi

2021

Lupus

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Systemic lupus erythematosus (SLE) often affects females of reproductive age and Cyclophosphamide, an alkylating agent leading to premature ovarian insufficiency (POF) and labelled category D for pregnancy is used as induction therapy for severe manifestations of lupus. There have been multiple case series reflecting variable outcomes of pregnancies after cyclophosphamide use for cancers and autoimmune diseases. With increasing maternal age, we have an increasing population of lupus patients who may wish to conceive after having received cyclophosphamide therapy. The objective of our study was to improve our understanding of the impact of cyclophosphamide exposure on fertility and pregnancy outcomes in patients with SLE. We retrospectively reviewed the charts of all patients who had received intravenous cyclophosphamide at our academic institute in the time period from 2000–2018 and identified 440 patients which included 157 female patients of reproductive age. There were 37 documented pregnancies after the cyclophosphamide infusion, of which 23 patients had successful outcomes; 4 elective abortion and 10 miscarriages. There were 17 patients who developed POF, of which 7 also had end stage renal disease. The average cumulative dose of cyclophosphamide in the patients who had successful pregnancy was 4080.37 mg compared to 2806.25 mg in those who had a miscarriage (p 0.164) and 5526.47 mg in those who developed POF (p 0.046). Using multiple regressions to evaluate risk factors impacting pregnancy outcomes, when taken as a set, the predictors including race, serological profile, exposure to steroids and Mycophenolate mofetil, age at cyclophosphamide infusion, age at pregnancy, and cumulative cyclophosphamide dose accounted for 46.29% of the variance in outcome of pregnancy (p 0.23) and 39.58% of the variance in development of premature ovarian failure (p 0.008). We noted statistical significance in the impact of maternal age at time of pregnancy (p 0.04) and duration of time between the last infusions to subsequent pregnancy (p 0.02) to pregnancy outcome. Our findings suggest that a longer time interval between the last cyclophosphamide infusion and subsequent pregnancy was favorable for a successful outcome and higher cumulative cyclophosphamide dose is more likely to be associated with premature ovarian failure.

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Section: Introductionmentioning

confidence: 99%

Pregnancy in patients with systemic lupus erythematosus after cyclophosphamide therapy

Sen

Kurl

Khosroshahi

2021

Lupus

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“…Breast cancer (BC) is the most commonly diagnosed malignancy during pregnancy with an estimated incidence of one in 3000 pregnancies [1,2]. The incidence of cancer during pregnancy is expected to rise further in developed countries, due to an increase in the mean maternal age at pregnancy and to an increasing incidence of cancer in young patients throughout the last decade [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Data about the obstetrical and fetal safety of chemotherapy administered during pregnancy are still not conclusive [7,8]. Several studies have reported higher rates of neonatal complications after in utero exposure to anticancer drugs [1,2,9], whereas others have found no significant differences [10,11]. The unwanted effects of chemotherapy administered during pregnancy depend mainly on the gestational stage; exposure during the first trimester is associated with a 10-20% risk of fetal malformations, whereas exposure during the second and third trimesters is significantly safer, with a fetal malformation rate similar to the unexposed population [12].…”

Section: Introductionmentioning

confidence: 99%

“…The unwanted effects of chemotherapy administered during pregnancy depend mainly on the gestational stage; exposure during the first trimester is associated with a 10-20% risk of fetal malformations, whereas exposure during the second and third trimesters is significantly safer, with a fetal malformation rate similar to the unexposed population [12]. Some of the effects on newborns can be referred, at least partially, to iatrogenic prematurity, i.e., the induction of anticipated delivery for medical reasons [1,2]. Others can be directly related to the chemotherapy administered and include premature labor, premature rupture of membranes (PROM), and intrauterine growth restriction (IUGR) [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity

Bar‐Joseph

Peccatori

Goshen-Lago

et al. 2020

Cancers

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Breast cancer is diagnosed in ~0.3% of pregnant women. Studies that have addressed gestational and neonatal outcomes of chemotherapy during pregnancy have demonstrated increased gestational complications including preeclampsia and intrauterine growth retardation. We hypothesized that anthracycline-induced gestational complications could be derived from direct toxicity on the placenta vasculature. Pregnant ICR mice (day E12.5) were treated with doxorubicin (DXR; 8 mg/kg) or saline, while their umbilical cord blood flow was imaged by pulse-wave (PW) Doppler. Mice were euthanized on day E18.5, and their embryos and placentae were collected for further analysis. Unlike control mice, the DXR-treated mice presented an acute change in the umbilical cord’s blood flow parameters (velocity time integral and heart rate interval), reduced embryos’ weight, reduced placenta efficiency, and modulation in vascular-related pathways of treated placenta proteomics. Apoptosis and proliferation were also enhanced, as demonstrated by TUNEL and proliferating cell nuclear antigen (PCNA) analysis. We further examined the placentae of patients treated with epirubicin (EPI), who had been diagnosed with breast cancer during pregnancy (weeks 27–35). The immunohistochemistry of the EPI-treated human placentae showed enhanced proliferation and apoptosis as compared with matched chemo-naïve placentae, as well as reduced neovascularization (CD34). Our findings suggest that anthracycline-induced vascular insult promotes placental toxicity, and could point to potential agents designated to offset the damage and to reduce gestational complications in pregnant cancer patients.

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“…11 In previous studies, among 24 females who treated for Hodgkin's disease in childhood, 17patients (70.8%) had normal gonadal function with regular menstrual periods. 12 Besides, chemotherapy has a negative influence on pregnancy outcomes 13 and increases the incidence of neonatal neutropenia. 14 It was unclear whether subsequent childbearing would increase the mortality risk of women with carcinoma.…”

Section: Introductionmentioning

confidence: 99%

<p>Outcomes and Experiences of Child-Bearing Women with Nasopharyngeal Carcinoma</p>

Chen

Kong

et al. 2020

CMAR

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Nasopharyngeal carcinoma (NPC) is more common among women in Southeast Asia. An important issue is whether it is safe for them to bear children after treatment and when it is safe to do so. We conducted this study to explore the relation between fertility and prognosis in child-bearing women with NPC. Patients and Methods: Child-bearing women were defined as young women between the ages of 18 and 30. A total of 127 eligible child-bearing NPC patients were identified from December 2003 to December 2014. The patients were divided into two groups, depending on whether or not they had post-therapeutic births. The Kaplan-Meier method was used for survival analyses. The Log rank test was used to compare two survival curves and the independent significances of different prognostic factors were assessed by Cox proportional hazards regression analysis. Results: The 5-year overall survival (OS) and disease-free survival (DFS) in the Childbirth group were significantly higher than those in the Non-Childbirth group (100% vs 88.8%, P = 0.026 and 100% vs 77.5%, P = 0.007, respectively). In the Childbirth group, no difference was found in the 5-year DFS between different birth interval times, from 1 to 5 years after treatment. The clinical stage was identified as the risk factor of OS (HR = 101.725, 95% CI: 2.160-4790.910, P = 0.019), and consequent childbirth after treatment was associated with favorable DFS (HR = 0.148, 95% CI: 0.034-0.643, P = 0.011). Conclusion: Post-therapeutic birth did not increase the mortality risk of child-bearing women with NPC. There was no significant correlation between the subsequent birth time window after treatment and the prognosis.

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Pregnancy outcomes in women exposed to cancer chemotherapy

Cited by 12 publications

References 23 publications

Pregnancy in patients with systemic lupus erythematosus after cyclophosphamide therapy

Pregnancy in patients with systemic lupus erythematosus after cyclophosphamide therapy

Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity

<p>Outcomes and Experiences of Child-Bearing Women with Nasopharyngeal Carcinoma</p>

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