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Women of reproductive age with type 1 diabetes mellitus (DM) and chronic kidney disease stage 5 after successful combined pancreas-kidney transplantation (CPKT) can experience spontaneous pregnancies with a favorable outcome. However, those pregnancies are associated with a high risk of complications: arterial hypertension, preeclampsia, premature birth, progression of diabetic retinopathy. During pregnancy, both gestational diabetes and spontaneous hypoglycemia can develop. This article presents a description of the clinical case of a 42-year-old patient with DM type 1, in whom pregnancy occurred 2 years after successful CPKT. Blood pressure was normal, the fundus condition was stable after previous treatment. The patient received tacrolimus and minimal dose of corticosteroids, at 13 weeks acetylsalicylic acid was prescribed to prevent preeclampsia. At 30 weeks nocturnal episodes of hypoglycemia appeared that were treated by additional intake of carbohydrates with an average glycemic index in combination with animal fats and proteins. At 36 gestational weeks caesarean section was performed due to premature rupture of membranes. A healthy girl was born with weight of 2140 g, height of 48 cm, Apgar score 7/8 points. The mother’s function of the kidney and pancreas grafts remained normal. Preconceptional counseling and multidisciplinary pregnancy management are important for patients after CPKT.

Pregnancy after kidney transplantation (KT) has become more common, but the risk of complications and adverse obstetric outcomes in this group of women remains high.Objective: to study pregnancy complications and outcomes in kidney recipients and renal graft (RG) survival after childbirth.Material and methods. The study included 22 pregnancies in 20 women with RG (transplants performed in 2006–2020). The comparison group consisted of 20 healthy women who had 20 pregnancies. Frequency and nature of pregnancy complications, neonatal health indicators, and pregnancy outcomes were evaluated. Graft survival was compared in the main group and in a group of 102 women after KT who did not have pregnancies.Results. Compared with healthy women, RG recipients had a higher rate of preeclampsia (25% and 0%, p = 0.047), fetal growth restriction (30% and 0%, p = 0.020), gestational diabetes (40% and 5%, p = 0.020), asymptomatic bacteriuria (35% and 5%, p = 0.044), preterm birth (60% and 0%, p < 0.001), and cesarean section (70% and 10%, p < 0.001). Median gestational age and birth weight were significantly lower in women with RG: 36.0 [33.9; 37.4] vs. 38.9 [38.9; 39.6] weeks, p < 0.001, and 2405 [2023; 2958] vs. 3355 [3200; 3690] g, p < 0.001, respectively. The rate of favorable pregnancy outcomes after KT was 81.8%, or 90% when early pregnancy loss is excluded. Two children were found to have genetic diseases passed from the mother. Graft survival did not differ between RG recipients with and without pregnancy, p = 0.272.Conclusions. Pregnancy outcomes in patients with RG are generally favorable, pregnancy and childbirth do not affect graft survival. When planning pregnancy after KT, it is necessary to consider the risk of complications and the possibility of transmitting genetic disorders to offspring.

Due to its effect on insulin resistance, ease of administration and favorable safety profile, metformin has been included in the recommendations of foreign medical communities for the management of pregnant women with hyperglycemia since 2008. However, in Russia, the use of any oral hypoglycemic agents during pregnancy is still contraindicated. However, recent studies demonstrate the safety and positive effects of metformin on pregnancy in patients with pregestational diabetes mellitus, polycystic ovary syndrome and gestational diabetes mellitus. In 2023, the Federal Service for Surveillance in Healthcare of the Ministry of Health of Russia updated the instructions for the medical use of Glucophage® and Glucophage®Long: pregnancy was excluded from the “Contraindications” section and moved to the “With caution” section. This resolution is intended to evaluate studies of the effectiveness and safety of metformin, as well as to study the experience of foreign colleagues and Russian legal aspects of prescribing metformin in the stages of preparation for pregnancy, during it and in the post-gravid period.

Kidney transplantation (KT), the optimal treatment for stage 5 chronic kidney disease (CKD), restores impaired fertility in most women of reproductive age. However, infertility occurs in some patients after successful KT. We present our own experience of overcoming secondary tubal infertility by in vitro fertilization (IVF). The patient was a 36-year-old with a transplanted kidney, who had lost two pregnancies in the past due to severe preeclampsia (PE). After the second attempt on cryo-thawed embryo transfer against the background of hormone replacement therapy, one embryo was transferred into the uterus, resulting in pregnancy. Gestational diabetes mellitus (GDM) was diagnosed in the first trimester, and a diet was prescribed. Immunosuppression with tacrolimus, azathioprine and methylprednisolone, prophylaxis of PE with low molecular weight heparin and antiplatelet drugs were administered during pregnancy. Elective cesarean section was performed at 37–38 weeks and a healthy boy was born, weighing 2760 g (25th percentile), 48 cm tall (36th percentile). A stay in the neonatal intensive care unit was not required. The baby is growing and developing normally, the mother’s renal graft function is satisfactory. So, IVF can be successfully used in post-KT patients with infertility issues, provided that the IVF program is carefully controlled, and the pregnancy is managed in a multidisciplinary manner.

Background: High-performance parallel next-generation sequencing (NGS) allows for identification of various maturity-onset diabetes of the young (MODY) subtypes also during pregnancy. As this method is expensive and time-consuming, it has proposed to use various predictors for the diagnosis of mutation in the hexokinase (GCK)/MODY2 gene, helping to select the patients for subsequent molecular genetic testing. Hyperglycemia due to MODY2 is commonly newly diagnosed during pregnancy; therefore, there is a search for factors specific to this mutation in pregnant women.Aim: To evaluate blood glucose variability in pregnant women with newly diagnosed hyperglycemia at early gestation and to determine the threshold value of the glycemic variability coefficient for pregnant women with a mutation in the GCK/MODY2 gene.Materials and methods: This observational single center study included 41 pregnant women with newly diagnosed early hyperglycemia (not meeting the criteria for manifest diabetes mellitus). Molecular genetic testing was performed in all of them. According to its results, they were retrospectively categorized into two groups: with early gestational diabetes mellitus (GDM, no mutations) and with hyperglycemia related to a mutation in the GCK/MODY2 gene. A comparative analysis of glycemic variability in the two groups was performed. Sensitivity and specificity of the cutoff value for the coefficient of variability as a diagnostic marker of MODY2 were also calculated.Results: The pregnant women with GDM had significantly higher age and body mass index (BMI) than those with MODY2 (p

Preeclampsia is an obstetric complication that is becoming a major cause of maternal and perinatal morbidity and mortality. The rate of preeclampsia in diabetes mellitus is 3 to 5-fold higher than in the population. Heparin is used for prevention of preeclampsia due to its experimentally shown important role in the trophoblast invasion and differentiation, as well as its influence on the production of proangiogenic factors. The paper gives a clinical case report that broadens our understanding on the preeclampsia pathophysiology and possibilities of its prevention. A 30-year old patient with no past history of serious physical illnesses had her two previous pregnancies with severe preeclampsia of early onset (arterial hypertension, massive proteinuria, thrombocytopenia, renal and hepatic insufficiency). Both babies were born extremely preterm (24 to 25 weeks of gestation) and died. Her hereditary background included type 2 diabetes in her maternal grandmother. At early terms of both pregnancies she had her fasting venous plasma glucose of 3.8 to 4.6 mmol/L (normal, < 5.1 mmol/L). Oral glucose tolerance test which had to be performed at 24 to 28 weeks of gestation, according to the protocol, was not performed. While planning for the third pregnancy, her body mass index was 29 kg/m2, with normal values of the blood pressure and renal function, no proteinuria and no evidence of the anti-phospholipid syndrome. In the 1st trimester, she had her fasting venous plasma glucose of 4.4 mmol/L. From the early term of her pregnancy, the patient was administered low molecular weight heparin; from the week 15, she was started with antihypertensive medications due to gestational arterial hypertension. Manifest diabetes was diagnosed at week 24 to 25 based on the results of the oral glucose tolerance test (4.96–10.42–11.46 mmol/L). With diet treatment, she had her postprandial glycaemia of up to 8.9 mmol/L, causing the initiation of basal-bolus insulin therapy from week 25 of gestation (0.4 U/kg), with achievement of good glucose control. At week 16, she had her sFlt1/PlGF level of 44 (high risk of preeclampsia). Molecular genetic assessment identified a HNF4A gene mutation, associated with MODY1. From week 34, she had moderate preeclampsia and fetal growth delay. An elective cesarean section was performed at week 38, with a healthy boy of 2300 g and 48 cm. After delivery, her diabetes was controlled by diet. The baby had an identical mutation. Thus, one cannot exclude a genetically determined link between complications of previous pregnancies and manifest diabetes diagnosed during the current pregnancy. Diagnosis of MODY1 in a pregnant patient would require the earliest initiation insulin treatment to prevent fetal macrosomia and neonatal hypoglycemia, as well as to prevent preeclampsia. The reason of successful outcome of this pregnancy could be related to heparin administration at the early terms of pregnancy that allowed for appropriate implantation and placenta formation, as well as for timely good glucose control.

Background: In the last years, an increase in numbers of pregnant patients with type 2 diabetes mellitus (T2DM) has been observed. Nevertheless, obstetricians/gynecologists and endocrinologists are not sufficiently aware of this problem. Aim: To analyze specific features of pregnancy course and outcomes in female patients with T2DM. Materials and methods: We performed a retrospective and prospective analysis of specific characteristics of pregnancy course and outcomes in 70 females with T2DM who were seen from 2008 to 2013. These 70 patients delivered 72 babies (including two twins). Results: Seventeen (24.3%) patients in their past history had perinatal losses or disability of babies. 81.4% of patients were obese. Twenty seven (38.6%) patients had arterial hypertension. Thirty (41.3%) patients had good diabetes control pre-pregnancy, whereas others were sub-optimally or poorly controlled. At trimester I, 45 (64.3%) of patients were treated with oral hypoglycemic agents. Thirteen (18.6%) of patients were hydramniotic and 4 (5.7%) were olygoamniotic. Mild gestosis was observed in 12, moderate, in 10 and severe, in 2 patients. Preterm delivery was performed in 9 (12.9%) of patients, among them in 5 cases due to a critical state of the fetus. Natural deliveries occurred in 34 (48.6%) of females. Deliveries of big fetuses were observed in 10 (13.9%) of cases. Thirty four (47%) of newborns had diabetic fetopathy, 4 (5.5%) had birth trauma. The rate of congenital abnormalities was 9.7%. All patients whose babies had congenital abnormalities, had concepted while taking sensitizers, and 7 of them were poorly controlled by that time. Any unfavorable perinatal outcome was registered in 32%. Conclusion: Female patients with T2DM have a high frequency of unfavorable perinatal outcomes (birth defects, disability in babies, prolonged intensive care in the neonatal period), and among complications of pregnancy, a high rate of gestosis (in particular in patients with baseline arterial hypertension). Improvement of perinatal and obstetric outcomes would require an optimization of management of such patients. Thus, it is reasonable to establish a multi-disciplinary team of specialists, including obstetrician/gynecologists, endocrinologists, internists and neonatologists, on the bases of centers for perinatal care or multifield hospitals with big in-patient department of obstetrics.

Reproductive disorders in women with pre-gestational diabetes mellitus lead not only to poorer fertility, but to complicated course and poor outcomes of pregnancy for mother and fetus. Compared to general population, patients with pre-gestational diabetes mellitus have higher frequencies of ovulation delay, ovarian dysfunction and infertility, and if they become diabetic before their puberty, they have later menarche and earlier menopause. All this is caused by functional disorders of hypothalamic-hypophyseal-adrenal axis and ovarian insufficiency with significant decrease in progesterone levels. Pre-conceptional existence of diabetes mellitus is associated with high probability of menstrual cycle disorders, infertility, and in case of pregnancy – with its complicated course (congenital malformations, miscarriage, fetoplacental insufficiency, pre-eclampsia). The risk of these abnormalities is increased in case of late diabetic complications and poor glucose control. Babies born to diabetic mothers, beyond fetopathy and fetoplacental insufficiency, suffer from long term central nervous system disorders that may lead to problems in social adaptation. There are no effective treatments for advanced clinical pre-eclampsia and uncontrolled fetoplacental insufficiency that necessitates the pregnancy to be terminated in the interests of mother or fetus. Due to this, in women with pre-gestational diabetes it is reasonable to implement preventive measures including those aimed at the main components of pathophysiology of a number of obstetric complications. In particular, to correct potential complications of pregnancy in women with diabetes mellitus, administration of active forms of folinic acid and normalization of eicosanoid balance with oral polyunsaturated ω-3 fatty acids is indicated during pregnancy planning and during gestation.

Background: The course of pregnancy and delivery in patients with diffuse toxic goiter (DTG) is often complicated by preeclampsia, fetoplacental insufficiency, placental abruption and associated with higher maternal and perinatal mortality. Aim: To study particulars of fetoplacental complex functioning in DTG. Materials and methods: We assessed pregnant patients with DTG (n = 92) and their newborns (n = 94). By the time of delivery, 86 of patients were clinically and biochemically euthyroid. Functions of fetoplacental complex (by levels of placental lactogen, α-fetoprotein, estriol, progesterone and cortisol) were assessed by radioimmune and immunoenzyme assays. Fetometrical parameters of fetuses were studied by ultrasound method. Complex assessment of placentas was done by light and electronic microscopy. Results: Eighty seven (94,6%) patients with DTG had combined complications of pregnancy. The most frequent were: the threat of termination of pregnancy, in 68 (73.9%) of cases, low placenta placement, in 23 (25%), anemia, in 56 (60.9%), pre-eclampsia, in 56 (60.9%). In 59 of patients (64.1%), fetoplacental insufficiency was diagnosed, with predominance of strain or exhaustion reactions. Critical status of fetoplacental complex was found in pregnant patients with uncontrolled DTG and duration of control of less than 20 weeks, as well as in pregnant patients with DTG relapses. The values of main hormones (placental lactogen, α-fetoprotein and progesterone) were below 10th percentile.According to the results of the ultrasound assessments, fetuses from mothers with DTG during gestation demonstrated decrease of the majority or percentile parameters, such as biparietal cranial size, fetal femoral length, abdomen diameter, that was especially prominent in the groups with relapsing DTG.Eighty eight of 94 newborns (93.6%) were born full-term. In total, every third baby (29.3%) had some degree of intrauterine developmental delay at birth. Among the cases with controlled DTG in mothers, there were 21.2% of such babies, whereas among those with DTG relapses, 40%. There was an association between the length of DTG control during pregnancy and mass and body parameters of newborns: the shorter was duration of DTG control during gestation, the higher was the risk of low birth weight fetuses (р < 0.05).Histological assessment of placentas from DTG patients showed changes of endothelial microlandscape with sprouting of cell plasmolemma, blood cell adhesion and fibrin deposition. In 86% of placentas there were stasis, sludge formation and thrombosis in cord vessels.Conclusion: Pregnancy starting during uncontrolled DTG is typically associated with primary placental insufficiency that is morphologically characterized by profound metabolic abnormalities (stromal fibrosis, immaturity of the villous tree, blood flow abnormalities and ischemia). Morphological and functional placental abnormalities correlated with duration of uncontrolled DTG and lead to high rate of intrauterine developmental delay.