The present case highlights the development of ICI-T1DM in a woman of childbearing age and successful delivery with adequate glycemic control using the AID system and complete response after ICI discontinuation. It was achieved through the patient’s strong willingness for childbirth, adequate understanding, and continuous communication between the tumor treatment team, the obstetrics and gynecology team, the diabetes support team, and the patient. As suggested by a consistent increase in ICI-T1DM [5] and association between higher risk of ICI-T1DM development and younger age [4], there is a potential for a future increase in the number of women of childbearing age with ICI-T1DM. We hope our experience proves to be invaluable in addressing those cases.

The patient had a strong willingness to undergo childbirth and underwent embryo cryopreservation soon after the cancer diagnosis. Maintenance of complete response resulted in her putting that willingness into action. ICI discontinuation and nonactive treatment may lead to lower overall survival than active treatment [6]. Thus, it is difficult for medical providers to recommend childbirth. The decision was based on the patient’s considerable willingness and adequate understanding of the risks to both the patient and her child. Due to the lack of evidence about cancer recurrence after ICI discontinuation, the patient and her oncologist decided to have a one-year follow-up period under careful monitoring. Using this period, obstetricians and gynecologists assessed reproductive function and prepared for pregnancy. As diabetologists, we introduced SAP and improved glycemic control. These cooperations beyond clinical departments resulted in delivery without lethal complications. Although the importance of care plans for cancer survivors has been noted [7], there is no clear landmark on care plans for those treated with ICIs.

The prevalence of ICI-T1DM was less than 1%, and the average onset age was over 60 years [4, 8]. Although younger age was reported to be a risk factor for ICI-T1DM development, the absolute number of ICI-T1DM patients under 60 years old was not large probably due to the less chance to use ICIs among younger patients [4]. These results suggested the rarity of ICI-T1DM in women of childbearing age. ICI-T1DM is characterized by a high incidence of diabetic ketoacidosis and low C-peptide [8]. ICI-T1DM often shows a fulminant phenotype as observed in our case. Our facility reported four out of six cases showed a fulminant phenotype [9]. In pregnant women with T1DM, high HbA1c is associated with both maternal and neonatal complications [10]. However, precise glycemic control during pregnancy is challenging despite the use of AID systems [11]. Furthermore, patients with undetectable C-peptide showed a significantly higher M-value than those with detectable C-peptide [12], suggesting difficulty in maintaining the narrow glycemic target range during pregnancy in such patients. In this case, the patient decided to use SAP with PLGS. With adequate patient’s management, the therapy minimized postprandial glycemic excursions and hypoglycemia, which resulted in achieving glycemic targets during pregnancy.

In this case, there were maternal and neonatal complications, including preeclampsia, preterm delivery, and congenital malformations, even under relatively good glycemic control. T1DM is associated with an increased risk of preeclampsia and preterm delivery [10, 13]. Hypospadias is one of the most common urogenital malformations and occurs in 0.3% of Asian male infants [14]. Bifid scrotum was associated with 33% of hypospadias [15]. The present patient was of primiparity, high maternal age (>=35), and prepregnancy diabetes, which were risk factors for hypospadias [16, 17]. A case series summarized that eight out of nine infants exposed to ICIs were preterm, and one of them had congenital malformation [18]. This might suggest that ICI use is associated with these complications. In this case, ovum pick up was performed 15 months after ICI discontinuation and embryo transfer was initiated 19 months after ICI discontinuation. These periods are much longer than the 5 months suggested by the EMA technical sheet [3], suggesting the limited effect of ICI on these complications. Because various factors may affect pregnancy and neonatal complications as mentioned above, the precise association between the complications and previous ICI use or ICI-T1DM remains ambiguous. Further research is needed to examine the association.

In conclusion, we reported an ICI-T1DM patient who experienced delivery after advanced cancer survival with ICI therapy. While the importance of care for cancer survivors has been acknowledged, care planning for those after ICI therapy has not been established. We hope that this report will provide one of the paths forward in optimizing the care plan.