Репозиторий Университета

© 2021, The Author(s). Background: An accumulating body of literature indicates that magnesium deficiency is associated with a number of hormone-related conditions (HRC) in women, and epidemiological studies are needed to assess its prevalence and risk factors. Here, we present a secondary analysis of data pooled from four large observational studies that assessed magnesium deficiency among pregnant women and women with HRC across the Russian Federation. Methods: The main objective of this analysis was to estimate the prevalence of magnesium deficiency in this population and to describe risk factors and comorbidities associated with low serum magnesium. Univariate logistic regression analysis was performed to identify the risk factors and comorbid conditions associated with an increased risk of low serum magnesium level. Results: A total of 983 pregnant women and 9444 women with HRC were eligible for analysis. Prevalence of hypomagnesemia (magnesium serum level cut-off < 0.66 mmol/L/< 0.8 mmol/L) was 34.0%/78.9% in pregnant women and 21.4%/54.8% in women with HRC. The highest prevalence of magnesium deficiency was observed for osteoporosis and climacteric syndrome. Risk factors included diastolic blood pressure, previous pregnancy complications, infections and edema for pregnant women, and age, body mass index, and various comorbidities for women with HRC. Conclusions: These results confirm the high prevalence of hypomagnesemia in pregnant women and women with HRC and underline the importance of routine screening, since risk factors are mostly non-specific.

© 2021, The Author(s). Background: An accumulating body of literature indicates that magnesium deficiency is associated with a number of hormone-related conditions (HRC) in women, and epidemiological studies are needed to assess its prevalence and risk factors. Here, we present a secondary analysis of data pooled from four large observational studies that assessed magnesium deficiency among pregnant women and women with HRC across the Russian Federation. Methods: The main objective of this analysis was to estimate the prevalence of magnesium deficiency in this population and to describe risk factors and comorbidities associated with low serum magnesium. Univariate logistic regression analysis was performed to identify the risk factors and comorbid conditions associated with an increased risk of low serum magnesium level. Results: A total of 983 pregnant women and 9444 women with HRC were eligible for analysis. Prevalence of hypomagnesemia (magnesium serum level cut-off < 0.66 mmol/L/< 0.8 mmol/L) was 34.0%/78.9% in pregnant women and 21.4%/54.8% in women with HRC. The highest prevalence of magnesium deficiency was observed for osteoporosis and climacteric syndrome. Risk factors included diastolic blood pressure, previous pregnancy complications, infections and edema for pregnant women, and age, body mass index, and various comorbidities for women with HRC. Conclusions: These results confirm the high prevalence of hypomagnesemia in pregnant women and women with HRC and underline the importance of routine screening, since risk factors are mostly non-specific.

© 2020 Objective: The association between the most severe types of placenta accreta spectrum disorders and caesarean scar pregnancy (CSP) poses the question of whether early diagnosis may impact the clinical outcome of these anomalies. The aim of this study is to report the outcome of cesarean scar pregnancy (CSP) diagnosed in the early (≤9 weeks) versus late (>9 weeks) first trimester of pregnancy. Study design: Medline, Embase and Clinicaltrail.gov databases were searched. Studies including cases of CSP with an early (≤9 weeks of gestation) compared to a late (>9 weeks) first trimester diagnosis of CSP, followed by immediate treatment, were included in this systematic review. The primary outcome was a composite measure of severe maternal morbidity including either severe first trimester bleeding, need for blood transfusion, uterine rupture or emergency hysterectomy. The secondary outcomes were the individual components of the primary outcome. Random-effect meta-analyses were used to combine data. Results: Thirty-six studies (724 women with CSP) were included. Overall, composite adverse outcome complicated 5.9 % (95 % CI 3.5−9.0) of CSP diagnosed ≤9 weeks and 32.4 % (95 % CI 15.7−51.8) of those diagnosed >9 weeks. Massive hemorrhage occurred in 4.3 % (95 % CI 2.3−7.0) of women with early and in 28.0 % (95 % CI 14.1−44.5) of those with late first trimester diagnosis of CSP, while the corresponding figures for the need for blood transfusion were 1.5 % (95 % CI 0.6−2.8) and 15.8 % (95 % CI 5.5−30.2) respectively. Uterine rupture occurred in 2.5 % (95 % CI 1.2−4.1) of women with a prenatal diagnosis of CSP ≤ 9 weeks and in 7.5 % (95 % CI 2.5−14.9) of those with CSP > 9 weeks, while an emergency intervention involving hysterectomy was required in 3.7 % (95 % CI 2.2−5.4) and 16.3 % (95 % CI5.9−30.6) respectively. When computing the risk, early diagnosis of CSP was associated with a significantly lower risk of composite adverse outcome, (OR: 0.14; 95 % CI 0.1−0.4 p < 0.001). Conclusions: Early first trimester diagnosis of CSP is associated with a significantly lower risk of maternal complications, thus supporting a policy of universal screening for these anomalies in women with a prior cesarean delivery although the cost-effectiveness of such policy should be tested in future studies.

© 2020 Elsevier B.V. Introduction and aim: Carbohydrate Deficient Transferrin (CDT) is one of the most used biomarkers for monitoring alcohol use in pregnancy. However, its effective application in this context is hampered by the demonstrated physiological progressive increase during pregnancy (even in abstinent women) of CDT values, which in the third trimester can reach values close or exceeding the cut-offs usually adopted in clinical and forensic diagnostics. The present work was aimed at the re-assessment of CDT reference values in pregnancy. Materials and methods: The CDT analysis was performed by a validated HPLC-UV Vis method on 284 serum samples of women with a physiological pregnancy and on 370 sera of non-pregnant woman from the general population (control group). All the samples were tested also for GGT for excluding alcohol abuse. The statistical analysis was performed using the MedCalc® Statistical Software. Results: The re-definition of the specific reference concentrations was carried out according to the Horn and Pesce Robust Method. The resulting CDT upper reference values were 1.45%, 2.01% and 2.05% in the first, second, and third trimester, respectively. Conclusions: In order to prevent the development of maternal and fetal prenatal alcohol exposure complications, the use of alcohol biomarkers, including CDT, has been proposed. However, this biomarker, in the monitoring of alcohol use in pregnancy, has so far been applied adopting the same cut-off used for general population without taking into consideration the progressive physiological increase of its value throughout the pregnancy. In the present study, a specific re-assessment of the CDT reference concentrations of each trimester is reported.

© 2019 Background: Iron (Fe), copper (Cu), and manganese (Mn) play a significant role in female reproduction and fetal development. At the same time, high levels of metals may exert toxic effects. Correspondingly, both excess and deficiency of essential trace elements were shown to be associated with female infertility and adverse pregnancy outcome, although the existing data are rather contradictory. Therefore, the objective of the present study was to reveal the potential role of altered iron, copper, and manganese status in female reproductive health problems through assessment of serum metal levels in healthy non-pregnant and pregnant women, as well as patients with miscarriage and primary infertility. Methods: A total of 150 healthy controls, 169 pregnant women (II trimester of pregnancy), 75 women with miscarriage, and 91 patients with primary infertility were enrolled. Serum metal levels were assessed using ICP-MS. Results: Pregnant women are characterized by a significant increase in serum Cu an Mn levels by 40% (p < 0.001) and 16% (p = 0.043) as compared to the controls, respectively. Serum Cu levels in women with miscarriage and infertility were 30% and 35% lower than those in pregnant women (p < 0.001). No significant difference in serum iron levels were observed between the control and pregnant women. Women who had miscarriage were characterized by 13% (p = 0.042) higher serum Fe levels as compared to the pregnant ones. Multiple regression analysis demonstrated that serum copper levels was significantly associated both with pregnancy (β = 0.436; p < 0.001) and reproductive health problems in women (β = −0.272; p < 0.001). The latter was improved significant after adjustment for serum Fe and Mn levels, age, and BMI (β = −0.431; p < 0.001). The model incorporating serum Cu, Fe, Mn, and anthropometric parameters accounted for 23% of variability in reproductive status (p < 0.001). Conclusions: It is proposed that the lack of pregnancy-associated increase in metal levels in miscarriage and infertility may be indicative of at least partial role of metal insufficiency in impaired pregnancy and reproductive function in general. However, detailed clinical studies as well as experimental investigations are required for assessment of the potential causes and mechanisms of the observed associations.

© 2019 The Author(s). Background: Cobalamin metabolism disorders are rare, inherited diseases which cause megaloblastic anaemia and other clinical manifestations. Early diagnosis of these conditions is essential, in order to allow appropriate treatment as early as possible. Case presentation: Here we report the case of a patient who was apparently healthy until the age of 20, when she presented with impaired renal function and normocytic anaemia. At the age of 34, when her first pregnancy resulted in an intrauterine death of a morphologically normal growth-restricted foetus, she was diagnosed with homocystinuria and methylmalonic aciduria due to cyanocobalamin C (cblC) defect, which was confirmed by molecular investigation. Consequently, hydroxocobalamin was administered to correct homocysteine plasma levels. This treatment was efficacious in lowering homocysteine plasma levels and restored anaemia and renal function. During a second pregnancy, the patient was also administered a prophylactic dose of low molecular -weight heparin. The pregnancy concluded with a full-term delivery of a healthy male. Conclusions: This case emphasises the importance of awareness and appropriate management of rare metabolic diseases during pregnancy. We suggest that women with late-onset cblC defect can have a positive pregnancy outcome if this metabolic disease is treated adequately.

© 2019 The Author(s). Background: Spontaneous pregnancy loss and implantation failure after assisted reproductive technologies (ART) are very common occurrences. Although 50-60% of all cases remains unexplained, various predisposing factors, including thrombophilias, have been identified. Thus, the potential benefit of a prophylaxis with low-molecular-weight heparins in improving outcomes has been often investigated over the years. However, the majority of studies are observational and results from randomized clinical trials (RCTs) are inconclusive, probably due to heterogeneity and limited sample size. To cover these unmet needs and to have further data mainly based on the real-life clinical management, we designed these multicenter registries. Methods: OTTILIA (Observational sTudy on antiThrombotic prevention in thrombophILIA and pregnancy loss) and FIRST (recurrent Failures in assIsted Reproductive Techniques) registries are two prospective, multicenter, observational studies to evaluate pregnancy or ART outcomes in consecutive women with previous reproductive failures after spontaneous or assisted conception, respectively. All enrolled women are observed from their first visit after positive pregnancy test (OTTILIA) or before commencing a new ART cycle (FIRST) until the end of pregnancy or ART procedure (negative pregnancy test/end of pregnancy, if successful cycle), respectively. Data are collected by means of questionnaires and recorded in a central database. Follow-up investigations are performed during hospital stay, routine clinical follow-up visits or telephone interviews. Primary outcome is live birth rate in the OTTILIA register and clinical pregnancy rate in the FIRST. Discussion: Although RCTs are the 'gold standard' for evaluating treatment outcomes, we believe that our registries represent a valid alternative in improving knowledge on mechanisms involved in reproductive failures and supporting future clinical decisions. Trial registration: NCT 02385461, retrospectively registered 5 March 2015 (OTTILIA); NCT 02685800, registered 10 February 2016 (FIRST).

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. A total of 100 women with early pregnancy loss were recruited and further classified into two subgroups: sporadic pregnancy loss and recurrent pregnancy loss; each subgroup consisted of 50 women. The control group included 56 women with normal pregnancies. Genotyping was performed by PCR with restriction fragment length polymorphism analysis. A statistically significant increase in the frequencies of TT genotype and T allele for DNMT3B rs2424913 polymorphism was found in the total patient group and in both patient subgroups in comparison with the control. Moreover, homozygous TT genotype was associated with increased risk of early pregnancy loss (both sporadic and recurrent). DNMT3B rs2424913 gene polymorphism in women can be used a marker of predisposition to early pregnancy loss and recurrent pregnancy loss.

© 2018 Walter de Gruyter GmbH, Berlin/Boston.  Despite intensive research, thromboembolism still accounts for significant maternal morbidity and mortality. We examined thrombophilia in patients with thromboembolism during pregnancy and evaluated the efficiency of antithrombotic prophylaxis in patients with thrombophilia for the prevention of recurrent thromboembolism. Sixty-eight women with a history of thromboembolism were managed during pregnancy, in light of their thrombotic history and the result of thrombophilia assessment. Group I (n=50) received prophylaxis with low molecular weight heparin (LMWH)±aspirin (50-100 mg/day) in preconception period or from the 1 st trimester, during pregnancy and at least 6 weeks postpartum. Group II (n=18) received LMWH±aspirin from the II to III trimester. Thromboses were associated with pregnancy in 27 patients (39.7%), with systemic diseases - in nine (13.2%), oral contraceptives use - 22 (32.3%), immobilization due to surgery and/or trauma, long flight - six (8.9%), septic complications - two (2.9%). Nevertheless, 24.5% of patients had no apparent provoking factor for the development of thrombotic complications. Thirty-seven (54%) patients with venous thromboembolism (VTE) had familial history of VTE, and 25 (36.7%) had personal history of pregnancy complications (fetal loss syndrome, preeclampsia and placental abruption) (P<0.05 vs. control). Thrombophilia was detected in 58 (85.3%). Usual thrombogenic polymorphisms [factor V (FV) Leiden and prothrombin G20210A, heterozygous forms] were revealed in 16 (23.5%) and eight (11.7%) patients, respectively. Antiphospholipid antibodies (aPL) circulation was found in 34 (50%) patients. Non-usual thrombogenic polymorphisms were identified in 44 (64.7%) of the women and hyperhomocysteinemia - in 30 (44.2%). In group I no one had severe obstetric complications. All the patients were delivered at term and all the babies were alive. In group II moderate-to-severe obstetric complications were noted: preeclampsia - in 11 (16.2%), severe preeclampsia - seven (10.3%), preterm delivery - in 18 (26.4%) patients from subgroup II (P<0.05). Women with a personal or a family history of thromboembolism and obstetric complications should be screened for thrombophilia. Beginning anticoagulant therapy early in such patients is effective not only for preventing recurring thrombosis but also preventing obstetric complications. Late prophylaxis after the completion of the trophoblast invasion therapy is much less effective.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We analyzed diurnal hemodynamic parameters (HR, systolic BP, and diastolic BP) recorded from two groups of edematous and preeclamptic pregnant women. The unidirectional character of changes in the control over the functional state of cardiovascular system was revealed except for the indices, which mark a pathological process: elevated diurnal BP in preeclampsia and diminished percentage of oscillation power in edematous patients. Uniformity of the regulatory changes in patients with and without arterial hypertension can be viewed as manifestation of allostasis developed by the cardiovascular system during pregnancy. In preeclampsia, the greater allostatic load was reflected by the changes in diurnal, daytime, and nighttime BP and in the circadian index calculated for HR, systolic BP, and diastolic BP. In edematous patients, elevation of allostatic load was indicated by the percentage of ultradian rhythms.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Changes in the levels of rennin, angiotensin II, and angiotensin (1–7) were studied during normal pregnancy. The blood was taken on gestation days 140-237 and 238-280. No significant changes in renin concentration were observed during normal pregnancy (p=0.423). The level of angiotensin II increased during normal pregnancy from 9.7±1.2 to 14.7±1.9 pg/ml (p=0.019). On the contrary, angiotensin (1–7) concentration decreased from 771.1±44.2 to 390.7±13.9 pg/ml (p<0.001). The shift in the proportion between vasoconstrictor angiotensin II and vasodilaltor angiotensin (1–7) attests to high predisposition of pregnant women to hypertension-related complications.

© 2017 Informa UK Limited, trading as Taylor  &  Francis Group. The objective of this article is to attract the attention of clinical physicians to the rare but extremely relevant clinical pathology of mesenchymal dysplasias (Marfan syndrome, Ehlers–Danlos syndrome, hereditary hemorrhagic telangiectasia) and especially specific characteristics of such diseases during pregnancy. Connective tissue pathology can cover different organs and systems, symptoms of the same disease can vary in different patients thus making diagnostics significantly difficult. Here clinical diagnostic criteria and methods of molecular diagnostics of diseases are described. The pathogenesis of mesenchymal dysplasias is not currently well understood. For the patients with mesenchymal dysplasias pregnancy is fraught with high risk of life-threatening complications. The preferred delivery method for such patients is caesarean section.

© 2018 Informa UK Limited, trading as Taylor  &  Francis Group Objective: The aim of this case series is to raise awareness of obstetric-related atypical haemolytic uraemic syndrome (aHUS) amongst obstetricians and gynaecologists. Study design: Data from 20 consecutive patients, aged 19–38, with obstetric-aHUS manifestation during or immediately after pregnancy are reported. Patients were diagnosed and treatment was initiated between 2012 and 2016. Results: Presentation of aHUS was mainly preceded by preeclampsia and/or haemolysis, elevated liver enzymes and low platelet count syndrome, other obstetric complications, or by diarrhoea. Thrombotic microangiopathy (TMA) was evident in all patients with signs of microangiopathic haemolysis (sharp decline in haemoglobin; mean 67 g/L), elevated lactate dehydrogenase (LDH; mean 2953.1 U/L), schistocytosis, thrombocytopenia (mean platelet count 52.5 × 109/µL), and acute kidney injury (AKI) (hypercreatininaemia, mean 456.4 µmol/L; oliguria or anuria). The majority of patients (80%) initially presented with arterial hypertension. Diagnosis of obstetric-aHUS was complicated, as multiple organs were affected. Time taken to make the diagnosis of aHUS delayed the initiation of fresh-frozen plasma infusions and plasma exchange (80% of patients) and subsequent eculizumab treatment (40% of patients). Maternal mortality was high (35%) as was foetal mortality (25%). Conclusions: Obstetric-aHUS is a serious condition characterized by multiple organ failure (MOF) and a high mortality rate. Presentation of obstetric-aHUS is preceded by various precipitating factors, suggesting pregnancy complications, and not the pregnancy per se, often induce aHUS in women with a genetic predisposition to its development. A delay in the correct diagnosis and initiation of the most effective treatment can have serious consequences, reinforcing the need to raise awareness of obstetric-aHUS.

© 2018, Dynasty Publishing House. All rights reserved. The article analyzes a favourable outcome of multiple pregnancy achieved after using assisted reproductive technologies and donor egg in a patient with recurrent pregnancy loss and combined thrombophilia.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To study the effectiveness, safety and tolerance of Viferon® (human recombinant interferon alpha-2b with antioxidants vitamins Е and С) as compared with standard therapy in complex treatment of mixed female urogenital infections during pregnancy and the effect of Viferon® on the formation of immunity in ontogenesis and during the early adaptation period of newborns. Patients and methods. The study included 70 women aged 18 to 40 years with mixed urogenital infections. The treatment group included 36 patients, who received etiotropic antimicrobial and antiviral therapy, underwent correction of immune status disorders and restoration of vaginal colonisation resistance. Along with standard therapy, patients of the treatment group received Viferon®, suppositories 500 000 IU, according to the schedule: 1 suppository 2 times/day every day for 10 days, then 1 suppository 2 times/day for 9 days with a 3-day interval. Aftre that, Viferon®, suppositories 150 000 IU 1 suppository 2 times daily every day for 5 days every 4 weeks until delivery. The control group comprised 34 patients who received standard therapy without interferon correction. All patients received standard therapy appropriate for their disease. Results. Among the patients receiving Viferon®, the development of placental insufficiency was recorded by 2 times more rarely. In the treatment group (Viferon®), fetal growth restriction (IUGR) was diagnosed only in 8.3%. In the control group, IUGR was found in 22% (OR + 2.65). In the treatment group, the incidence of fetal CMV infection was reduced by 16 timesd anf of herpesvirus infection type 2 – by 10 times. In the group of patients who did not use Viferon®, the share of newborns with CNS lesions amounted to 18.4%, whereas in the treatment group it approached 6.5% (OR –2.83). Inclusion of Viferon® in complex therapy resulted in a lower incidence of infectious lesions of the skin and mucous membranes of the newborn infants (amniotic fluid infection syndrome) by 5.8 times. Colclusion. The use of Viferon® (human recombinant interferon alpha-2b with antioxidants vitamins Е and С) suppositories in complex therapy in pregnant women with infection promotes a faster elimination of viruses, a significant decrease of the signs of threatened miscarriage, premature labour, risk for developing PI and IUGR, associated with inflammatory process (p < 0.05).

© 2018 Izdatel'stvo Meditsina. All rights reserved. The right drug at the right dose administered to a patient in time is the goal which all medical specialists aim at when prescribing medicines to patients. Pregnancy is a condition when the principle of personalized pharmacotherapy is especially relevant. Due to the developing fetus and the occurring changes in the maternal organism, the selection of drug therapy during pregnancy is especially difficult for a clinician. This issue is tightly intertwined with clinical pharmacogenetics since the genetic code of a woman that determines the activity of the liver cytochrome, the fetus-placental barrier, and renal clearance contributes to the peculiarities of the drug metabolism during pregnancy. Additional data provides the opportunities to form therapeutic models and to determine the ways of personifying pharmacotherapy in pregnancy. The purpose of this review is to summarize the available data on the pharmacogenetics of antihypertensive drugs used during pregnancy.

© 2018 Dynasty Publishing House. All rights reserved. Thrombocytopenia (TCP) includes a huge range of diseases and syndromes with different causes and pathogenetic mechanisms. TCP is defined when platelet count less than 150 × 109/L. the Diagnostic search when TCP should begin with the establishment of a pathogenic variant with subsequent verification of the main reasons for TCP. This allows you to select pathogenetic therapy of the disease (glucocorticoids, immunosuppressants, anticoagulants) and to influence the basic process.

© 2018 Dynasty Publishing House. All rights reserved. Exosomes (vesicles with the size of 30-150 nm) are formed in multivesicular bodies (MVB) by invagination of early endosome membranes and mediate intercellular interactions. Exosomes are secreted by various kinds of cells, their content might be represented by proteins, lipids and nucleic acids, which reflect the functional state of donor cells. The effect of exosomes on recipient cells depends on their quantity and characteristics of their «load». Comparatively recently, placental exosomes secreted by various placental cells have been isolated from blood of pregnant women. A specific protein - placental alkaline phosphatase (PLAP) - has been determined for these exosomes. PLAP-positive exosomes can be found in maternal blood as soon as in the first trimester of pregnancy, their number increases with maturation of the foetus and reaches its maximum by the moment of birth. Although the functional significance of placental exosomes is still investigated, some authors relate changes in the placental exosome profile (their number and composition) to placental dysfunction underlying the development of complications of pregnancy. Isolation of exosomes from blood of pregnant women (fluid biopsy) and determination of their biological characteristics might be regarded as early noninvasive diagnosis of structural and functional placental abnormalities. The appearing evidence of blastocyst-secreted exosomes and their role in modulating maternal immunity and endometrial receptiveness during implantation are also promising. The review presents data about the biogenesis, structure and functions of exosomes and the role of placenta-associated exosomes in the development of physiological and complicated pregnancy, and also about the possibility of using exosomes as a marker of the state of the blastocyst in assisted reproductive technologies, in particular, in oocyte donation and surrogate motherhood.

© 2018 Dynasty Publishing House. All rights reserved. Post-partum depression arises following pregnancy and childbirth, it is a severe disorder threatening the wellbeing of both mother and baby. In the affected families, there is a higher risk of the child's impaired emotional, social and cognitive development. Post-partum depression is one of the most common complications of the postnatal period. The disease prevalence varies from 6.5 to 12.9% and more in countries with low and middle levels of income and life. We analysed 62 Russian and worldwide literature sources published in the PubMed, Google Scholar databases and in Russian medical periodicals over the period 2002-2017 on this theme, we also translated the original Edinburgh Postnatal Depression Scale. This systematic review presents current ideas of the causes of postpartum depressions, methods of treatment and prevention.

© 2018 Dynasty Publishing House. All rights reserved. Objective: Development and justification of a differentiated approach to diagnosis and treatment of ectopic extratubal pregnancies. Patients and methods: 37 patients with histologically verified diagnosis «Ectopic pregnancy» were examined, in whom the ovum was located outside the uterine tubes. In 26 cases it was cervical pregnancy, in 8 - ovarian pregnancy, and 3 pregnancies within a caesarean scar. Diagnostic and treatment methods: 2D- and 3D-transvaginal echography, including power Doppler sonography; hCG testing in blood and urine, laparoscopy, hysteroresectoscopy. Results: A system of examining and treating patients with rare ectopic pregnancies has been developed, in which step-by-step measures for optimization of diagnostic and therapeutic processes are presented. The main attention is paid to organ-sparing technologies, including metroplasty and intrauterine surgery in caesarean scar ectopic pregnancy, and also intrauterine surgery in cervical pregnancy. Conclusion: The presented system permits to optimize diagnosis and treatment of patients with ectopic extratubal pregnancies with preservation of the reproductive function.