Congenital Infections in Neonates of Women With Liver or Kidney Transplants.

BACKGROUND: Immunosuppressive therapy is associated with an increased risk of pregnancy complications and may have adverse effects for the newborn. The aim of this study was to determine the frequency and the type of early congenital infections and to assess typical markers of infections in neonates of liver and kidney recipients. METHODS: A retrospective analysis of 71 neonates born to either liver (39 cases) or kidney transplanted women (32 cases) was conducted. The rate and the type of newborns' infections as well as laboratory and bacteriologic markers of infections were analyzed. RESULTS: There was no significant difference in the frequency of congenital infections between the LT and KT groups (8 vs 7 cases; P = .879).). The rate of infections was not significantly higher in both groups compared with the general population. Infections were detected in 23.9%, 13.6%, and 26.6% of neonates born to mothers using tacrolimus, cyclosporine, and azathioprine respectively. No significant differences in white blood count or levels of neutrocytes and lymphocytes were observed between the groups. No abnormalities in white blood smear, but 1 case of leukopenia in the kidney transplant group, were detected. CONCLUSIONS: The rate of congenital infections in neonates of allograft recipients is not significantly higher than in the general population. Immunosuppressive regimens with azathioprine seem to carry the greatest risk, it is a little lower in the tacrolimus group, and cyclosporine-based regimens have the lowest risk of congenital infections. Differences were not statistically significant. Prenatal exposure to immunosuppressive agents seems not to be associated with any hematologic disturbances in white blood count and white blood smear.

Multiple types of high-risk human papilloma virus in the lower genital tract of a female kidney recipient: a case report.

We present a case of a female kidney recipient who was infected with 3 types of high-risk human papilloma viruses. An infection in the lower genital tract led to the development of both neoplastic cervical lesions and vulvar cancer.

Menstrual function in female liver transplant recipients of reproductive age.

BACKGROUND AND AIM: End-stage liver failure is associated with severe abnormalities in menstrual and reproductive function. These abnormalities may be reversed by successful orthotopic liver transplantation (OLT). The aim of the study was to investigate menstrual patterns and sex hormone profiles among female liver transplant recipients of reproductive age. METHODS: The study group consisted of 24 women of reproductive age with end-stage liver failure who underwent successful OLT. Menstrual patterns and sex hormone profiles were analyzed before as well as 3 and 12 months after OLT. Twenty-seven healthy women of reproductive age served as controls. Biochemical parameters of liver function were assessed before and after OLT. RESULTS: Amenorrhea was the most commonly observed abnormality of menstrual cycle in women with end-stage liver failure (71% of patients). The recurrence of regular menstrual cycles was observed in 35% of patients 3 months after OLT. The percentage increased to 70% at 1 year after grafting and was clearly associated with stabilization of liver function. Similar levels of follicle stimulation hormone (FSH), luteinizing hormone (LH), prolactine (PRL), and testosterone (T) as well as lower levels of estradiol (E(2)), dehydroepiandrostendione sulphate (DHEA-S), and progesterone, (P) were observed in patients with liver failure compared with healthy women. We observed normalization of E(2) and DHEA-S levels after OLT. CONCLUSIONS: Amenorrhea, the most common menstrual disturbance in women with end-stage liver failure, may be reversed by OLT. One year after OLT menstrual bleedings were noted in 74% of patients of reproductive age. The recurrence of reproductive function indicated the need for effective and safe family planning methods in that group of patients.

Operative treatment of endometrial hyperplasia in kidney graft recipients: report of seven cases.

OBJECTIVES: The high rate of abnormal uterine bleeding associated with endometrial hyperplasia has been observed in women after kidney transplantation. The great majority of these premalignant lesions regress after conservative treatment, mostly with progestagens. There are cases, however, of persistent or recurrent hyperplasia requiring operative treatment. MATERIALS AND METHODS: We report seven cases of endometrial hyperplasia in kidney graft recipients treated with hysterectomy after failure of conservative treatment. The presence of typical risk factors of endometrial hyperplasia and cancer were analyzed as well as their clinical courses and treatment methods. RESULTS: The age of the patients ranged from 35 to 50 years (mean, 42.7). Among typical risk factors, we observed obesity, diabetes, arterial hypertension, and nulliparity in the study group. All patients reported abnormal uterine bleeding and developed anemia. Women underwent two to four dilatation and curettage procedures. Progestagens (medroxyprogesterone or lynesterol) were administered for 3 to 9 months. The initial treatment was ineffective in two cases; in the remaining five cases endometrial hyperplasia recurred within 3 to 12 months. Pathologic findings after hysterectomy in all patients confirmed non-atypical endometrial hyperplasia. CONCLUSION: Hysterectomy is the treatment of last resort for premalignant endometrial lesions. It should be considered in all cases of recurrent or persistent endometrial hyperplasia. It may protect immunocompromised kidney graft recipients from heavy bleeding, severe anemia, and most of all, the of endometrial cancer development.

Oral and transdermal hormonal contraception in women after kidney transplantation.

AIM: The aim of the study was to assess the safety of low-dose oral or transdermal hormonal contraception in kidney recipients. MATERIALS AND METHODS: Twenty-six kidney recipients, aged 18 to 44 years (mean, 31.0) took low-dose contraceptive pills, and 10 kidney recipients, aged 22 to 36 years (mean, 31.4) used transdermal contraceptive systems. Contraception was administered for a period not shorter than 18 months. At the onset of therapy all patients showed stable graft function. The main indication for therapy was effective contraception. Additional indications were mild ovarian cysts and irregular or profuse menstruations. The pills consisted of 20 to 35 microg of etinyl estradiol and generation III progestogen. The contraceptive patch released 20 microg of etinyl estradiol and 150 microg of norelgesromin daily. RESULTS: No case of pregnancy was noted. Oral contraception was discontinued in two cases, in one case due to profound thrombophlebitis of the lower extremity and in the other case deterioration of liver function. No other side effects or symptoms of intolerance were reported. Hormonal contraception did not significantly influence body mass index, mean blood pressure, serum creatinine, or other biochemical parameters. CONCLUSION: Despite the presence of relative contraindications, mainly arterial hypertension and impaired liver function, hormonal contraception should be considered in female kidney recipients to be a highly effective contraceptive method that additionally regulates menstrual bleeding, protects from development of mild ovarian cysts and seems to positively influence women's well-being. The transdermal mode of administration may diminish the chance for drug interactions and therefore be safer for patients.

Mode of delivery in women after liver transplantation.

AIM: A high rate of cesarean sections has been reported among high-risk pregnancies in liver transplant recipients. The aim of this study was to analyze the course of deliveries and the indications for cesarean sections in women after liver transplantation. MATERIALS AND METHODS: From 2001 to 2006, we noted 21 deliveries in 17 liver recipients. The mean age of women was 27.9 +/- 6.6 years and the mean time from transplantation to pregnancy was 4.3 +/- 3.6 years. Most patients were primigravidas on tacrolimus-based immunosuppressive regimens. We retrospectively analyzed obstetric data regarding the delivery and the early puerperium. RESULTS: We noted 6 vaginal deliveries (29%) and 15 cesarean sections (71%). Mean gestational age in the group of vaginal deliveries was 37.6 +/- 2.2 weeks. No labor complications were noted. All neonates were delivered in a good state (Apgar score from 8 to 10 points) with mean birth weight of 2725 g. All cesarean sections were performed for obstetric indications: fetal distress, breech presentation, intrauterine growth retardation, or complications related to premature labor. Mean gestational age was 37.0 +/- 1.9 weeks. The Apgar scores ranged from 4 to 10 points; mean birth weight was 2787 g. The mean period of hospitalization after surgical labor was 4 days longer compared with the vaginal delivery group. CONCLUSION: The high rate of cesarean sections (71%) in liver recipients is associated with a great incidence of obstetric complications of pregnancy. Safe and uneventful vaginal delivery is possible with growing experience in the management of pregnant transplanted women.

Low-dose hormonal contraception after liver transplantation.

OBJECTIVES: End-stage liver failure is associated with extremely reduced fertility. After liver transplantation, restoration of menstrual function is observed; thus effective contraceptive methods should be employed in patients who do not plan to conceive. The aim of this study was to assess tolerability and safety of hormonal contraceptives in female liver transplant recipients. MATERIALS AND METHODS: We retrospectively analyzed data on 15 female liver graft recipients, aged 24 to 35 years, who used hormonal contraceptives after liver transplantation for a time not shorter than 12 months. The period from grafting to administration of hormonal contraceptives varied from 6 months to 7 years. Biochemical parameters of liver function, fasting glucose levels, body mass index (BMI) as well as blood pressure were monitored at 0, 3, 6, and 12 months of therapy. Side effects of the treatment were noted on regular follow-up examinations. RESULTS: No case of pregnancy or graft rejection was observed on therapy. Changes of biochemical parameters were not significant (aspartate transferase 22.92 +/- 6.67 vs 25.54 +/- 7.90, alanine transferase 22.08 +/- 5.66 vs 24.27 +/- 7.57, total bilirubin 0.96 +/- 0.17 vs 1.02 +/- 0.15). Blood pressure and BMI remained stable in the group. None of the patients discontinued therapy for medical indications. CONCLUSION: Hormonal contraception was administered as soon as liver transplant function was stable. It was effective, well tolerated, and did not seem to impair graft function. However, a long-term prospective study is necessary to assess the safety of hormonal contraception in transplant recipients.

Menstrual cycle and sex hormone profile in perimenopausal women after liver transplantation.

UNLABELLED: Excellent long-term outcomes of transplant patients let many female liver-recipients experience perimenopausal problems. This study assessed menstrual patterns and sex hormone profiles in women of perimenopausal age who experienced end-stage liver failure treated by transplantation (OLT). MATERIALS AND METHODS: Menstrual patterns, sex hormone profiles, and biochemical parameters of liver function were analyzed before and after OLT in 13 liver-transplanted patients of perimenopausal age. Nineteen healthy perimenopausal women served as controls. RESULTS: The most common abnormality of the menstrual cycle observed in the study group was secondary amenorrhea, which affected six liver-transplanted women. Three months after OLT amenorrhea was still observed in six patients, regular menstrual cycles in six and irregular bleeding in one graft recipient. One year after transplantation regular menstruations were noted in four, irregular bleeding in four, and secondary amenorrhea in five liver-transplanted women. Similar levels of follicle stimulating hormone, luteinizing hormone, prolactin, progesterone and testosterone as well as lower levels of estradiol and DHEA-sulfate were observed in patients with liver failure, both before and after grafting, compared with healthy women. After OLT E2 levels increased from 32.05 +/- 18.04 to 49.12 +/- 22.21. CONCLUSIONS: One year after OLT disturbances in menstrual patterns affect most (69%) perimenopausal female liver recipients. Both before and after OLT significantly lower levels of estradiol and DHEA-S were observed in transplanted patients compared with healthy controls. Hormonal therapy of amenorrhea or irregular menstruations may be required in that group of patients.

High rate of endometrial hyperplasia in renal transplanted women.

UNLABELLED: A high rate of endometrial hyperplasia, an estrogen-dependent premalignant lesion of the endometrium, has been observed among female kidney allograft recipients. The aim of the study was to evaluate the incidence of endometrial abnormalities among renal transplanted women with abnormal uterine bleedings. MATERIAL AND METHODS: A retrospective analysis compared 45 renal transplanted women who underwent dilatation and curettage for abnormal uterine bleeding between January 1999 and September 2004 with 90 consecutive, nontransplanted, control patients who underwent dilatation and curettage for the same reason in 2004. RESULTS: Thirty-one cases (69%) of endometrial hyperplasia and one case (2%) of endometrial cancer were detected among the renal allograft recipients. The majority of transplant patients (28 cases, 62%) developed endometrial hyperplasia without atypia successfully treated with progestagens. There were 29 cases (32%) of hyperplasia without atypia, 2 cases (1%) of atypical hyperplasia, and 4 cases (4%) of endometrial cancer in the control group. CONCLUSIONS: Renal transplanted women seem to have an extremely high risk of endometrial hyperplasia. The majority of cases may be successfully treated with progestagens. Immunocompromised renal graft recipients, however, show other risk factors for carcinogenesis. Thus, frequent clinical surveillance should be recommended in this group of patients, also because there is conflicting evidence with regard to the risk of progression to carcinoma among untreated patients.

Function of the ovaries in female kidney transplant recipients.

OBJECTIVES: One of the effects of an improved general health state after successful kidney transplantation in women of reproductive age is recurrence of regular menstrual function. MATERIALS AND METHODS: Sixty-three ovarian cycles in female kidney transplant recipient, aged from 18 to 44 years, at 1.5 to 15 years after transplantation, were compared with 50 cycles of healthy women. We monitored the menstrual cycle duration as well as follicle stimulation hormone (FSH), leutinizing hormone (LH), estradiol, progesterone, prolactin, creatinine, and testosterone serum concentrations as well as hematocrit and obtained sonographic observations of ovarian follicle growth and ovulation. RESULTS: Of the recipients, 68.1% had regular menstrual cycles. Ovulatory cycles were observed in 45% of patients. Estradiol concentration established in the first phase of the cycle was significantly higher among the transplanted group (mean value 226.86 +/- 97.45 pg/mL vs 140.00 +/- 61.00 in the controls). A significantly lower level of progesterone (15.05 +/- 17.34 ng/mL vs 30.79 +/- 18.48 ng/mL in the controls) and of testosterone were observed in kidney recipients. Other hormonal parameters did not differ significantly between the groups. CONCLUSIONS: Similar serum FSH, LH, and prolactin concentrations as well as increased levels of estrogens were observed in kidney transplant recipients compared with healthy nonrecipients. The rate of ovulatory cycles in regularly menstruated kidney graft recipients was similar to that of healthy women. Stabilization of graft function resulted in restoration of normal ovarian hormone metabolism and ovulatory cycles in female kidney transplanted recipients.

Safety and efficacy of hormonal therapy in menopausal kidney-allograft recipients.

AIM: A higher risk of premature menopause and osteoporosis has been observed in female kidney-allograft recipients, providing particular indications for hormonal therapy. We have summarized our 10-year-experience with hormonal therapy in menopausal kidney transplant recipients. MATERIALS AND METHODS: From 1995 to 2004, hormonal therapy was administered to 54 kidney transplant recipients. At onset of therapy the ages of the women ranged from 31 to 52 years, and the period from transplantation from 3 months to 13 years. The mean time on therapy was 4.2 years. All patients received transdermal estradiol (E(2)) in combination with oral progestin. RESULTS: Total regression of climacteric symptoms was reported in 75% of patients. After 3 months of the therapy follicle stimulating hormone (FSH) and E(2) levels normalized: FSH from 129 +/- 30.1 IU/L to 38.3 +/- 26.1 IU/L and E(2) from 18.5 +/- 5.8 pg/mL to 98.6 +/- 33.2 pg/mL. No significant change was noted in serum creatinine. Eleven patients developed abnormal uterine bleeding but none had premalignant or malignant lesions of the uterus on endometrial curettage. No incidence of breast cancer was noted during mean treatment period of 5.2 years. Seventeen patients discontinued therapy for medical indications: one for profound thrombophlebitis and 16 for significant deterioration of liver function. Twelve women made their own decision to discontinue therapy. CONCLUSION: Hormonal replacement therapy was effective with no negative impact either on graft function or sex organs among kidney transplant recipients. Liver parameter monitoring seemed to be essential for safe continuation of treatment.

Outcome of four high-risk pregnancies in female liver transplant recipients on tacrolimus immunosuppression.

Pregnancies in women after liver transplantation are considered high risk due to the greater rate of complications observed in immunosuppressed graft recipients. We report successful outcomes of four high-risk pregnancies in female liver transplant recipients on tacrolimus-based immunosuppression. The patients, aged 23 to 32 years, at the time of conception were 12 to 59 months from transplantation (mean 30 months). Preterm labor was the most important pregnancy complication observed in these patients. One episode of acute graft rejection was observed. A variable demand for tacrolimus was noted during pregnancy. Despite complications all four pregnancies were successful. The mean gestational age at delivery was 34.4 weeks. The birth weight of the newborns varied from 1410 to 3490 g (mean 2303 g) and the mean Apgar score was 8. No structural malformations or early complications were observed in the newborns. Excluding the patient with acute rejection, the remaining three cases showed all liver parameters to remain stable.

Multiple neoplastic lesions of the lower genital tract in a human papilloma virus-infected kidney-pancreas allograft recipient: a case report.

States of immunodeficiency are associated with an increased rate of certain cancers. Immunosuppressed allograft recipients are at high risk of Human Papilloma Virus (HPV)-related de novo malignancies. A female pancreas plus kidney transplant patient developed multiple genital malignancies within 6 years. The genome of human papilloma virus type 16 was detected in malignant lesions obtained from surgical procedures. All detected lesions were removed at an early state of development.

Pregnancy and delivery after liver transplantation.

AIM: According to statistics, women constitute one-third of all liver recipients and approximately 75% of female recipients are of reproductive age. Successful liver transplantation in these patients results in the restoration of menstrual function and fertility. The aim of this study was to assess the course of pregnancy and delivery in liver-transplanted women. MATERIALS AND METHODS: We retrospectively analyzed data of 138 liver-transplanted women, aged from 18 to 63 years, who underwent regular gynecological evaluations. Among 77 patients of reproductive age, 11 women conceived and delivered babies. RESULTS: All patients have successfully delivered. The mean gestation age at delivery was 36.5 weeks. All neonates were delivered in a good state with no congenital abnormalities. Common pregnancy complications were preterm birth, anemia, intrahepatic cholestasis, and infection. In 1 case, graft rejection was observed due to willful discontinuation of immunosuppressive therapy. Two spontaneous vaginal deliveries and 9 caesarean sections were performed. All caesarean sections were performed for obstetrical indications: fetal intrauterine asphyxia (n = 4), breech presentation (n = 2), threatening intrauterine infection (n = 2), and preterm twin delivery (n = 1). CONCLUSION: High-risk pregnancies in liver-transplanted women are generally associated with good outcomes, although an increased rate of preterm labor, intrauterine infections, anemia, and cholestasis were observed. Pregnancy did not seem to impair graft function or accelerate rejection in patients receiving immunosuppressive therapy.

Angiogenic activity and IL-8 concentrations in peritoneal fluid and sera in endometriosis.

OBJECTIVES: During menstruation endometrial fragments are transported into the peritoneal cavity where they form endometriotic lesions. Angiogenesis is proposed as one of the mechanisms in endometriosis pathogenesis. The aim of the study was to determine the angiogenic activity and interleukin 8 concentrations in peritoneal fluid and sera in endometriosis. METHODS: Angiogenesis was determined in cutaneous assay in Balb/c mice; IL-8 concentrations were measured by ELISA test in sera and peritoneal fluid of 32 control and 56 endometriosis patients. Wilcoxon and Mann-Whitney tests and Spearman rank correlations were used in statistical analysis. RESULTS: Peritoneal fluid and sera from the examined group had higher angiogenic activity and interleukin 8 concentrations. There was correlation found between AFS and neovascularization induced by sera and PF of patients with peritoneal lesions. CONCLUSIONS: Angiogenesis plays an important role in pathogenesis of endometriosis. Although IL-8 takes part in neovascularization, there are other factors modulating angiogenesis in endometriosis.