Multiple pregnancies in women after renal transplantation

Multiple pregnancies in women after renal transplantation

European Journal of Obstetrics & Gynecology and Reproductive Biology 84 (1999) 107–110 Case Report Multiple pregnancies in women after renal transpl...

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European Journal of Obstetrics & Gynecology and Reproductive Biology 84 (1999) 107–110

Case Report

Multiple pregnancies in women after renal transplantation Case report that rises a management dilemma Boris Furman, Arnon Wiznitzer*, Rinat Hackmon, Joseph Gohar, Moshe Mazor Department of Obstetrics and Gynecology, Soroka Medical Center, Faculty of Health Sciences Ben-Gurion University of the Negev, P.O. Box 151, Beer-Sheva, Israel Accepted 4 November 1998

Abstract Objectives: To report the pregnancy outcome in women with multiple pregnancies after renal transplantation. Materials and methods: We report two cases of multiple pregnancies (triplets and twins) in renal allograft recipients and evaluate the pregnancy courses and maternal and fetal outcome of these patients. Results: After fetal reduction from triplet to twin pregnancy the first patient delivered healthy twin babies at 36 weeks gestation. Six months after delivery the woman is well with no signs of renal function impairment. Although the second patient did not meet the optimal criteria for consideration of pregnancy in renal transplant recipients, she delivered normal twin babies at 33 weeks’ gestation. Maternal complications during pregnancy included preeclampsia, mild deterioration of renal function tests, and secondary complications due to drug therapy that was resolved after delivery. No graft rejection episodes were noted in either case during pregnancy. Conclusions: Multifetal gestation in renal allograft recipients represents a high-risk pregnancy that should be managed at a tertiary care institution. The overall outcome in properly consulted patients can be considered favorable. Based on our limited experience with two cases, we suggest reduction of triplets to a twin pregnancy which is consistent with the current literature data.  1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Multiple pregnancy; Renal transplantation; Fetal reduction; High-risk pregnancy

1. Introduction The possibility of conception in women of reproductive age after renal transplantation raises and needs appropriate counseling. With improvement of renal function prior to pregnancy, a more satisfactory perinatal outcome can be accomplished. However, patients undergoing renal transplantation during pregnancy demonstrate serious complications, such as preeclampsia, premature delivery, intrauterine growth restriction and rejection of the graft [1]. Ideally, a woman considering pregnancy after renal transplantation should delay her pregnancy planning for a period of 2 years after the procedure when no evidence of graft rejection is present at the time of counseling. There *Corresponding author. Tel.: 1972 7 6400542; fax: 1972 7 6400559.

should be little or no proteinuria and hypertension, but if present they should be minimal and well controlled [2]. In addition, women suffering from chronic renal failure usually demonstrate loss of libido, anovulation and amenorrhea [3]. As a result, pregnancy occurs in only one out of 200 reproductive age women in dialysis therapy and a very few of these result in livebirth at term [4]. In contrast, many women note the return of menstrual cycles within 2 years of renal transplantation. Thus, the opportunity for conception is partially restored [3]. However, in some patients induction of ovulation is necessary in order to achieve pregnancy. Therefore, the possibility of multiple pregnancies in those patients is increased. Patients with multiple pregnancies after renal transplantation represent a high-risk group that creates a management dilemma. The obstetric outcome includes

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maternal complications as well as adverse perinatal outcome. Therefore, the question arises as to whether it is legitimate to treat those patients using assisted reproductive technology. On the other hand, appropriate precautions can be used to avoid complications by careful use of ovulatory induction agents and by a limited number of embryos transferred in IVF treatment. In addition, selective multifetal pregnancy reduction appears to be effective for improvement of perinatal outcome. There is limited data in the literature regarding the management of kidney transplant patients with a twin pregnancy [5]. Recently, two patients with multiple pregnancies after renal transplantation were treated in our high-risk pregnancy unit at Soroka Medical Center. One of the patients had triplets and the second had a twin pregnancy.

2. Case 1 A 25-year-old (2-0-1-0) was admitted at 12 weeks’ gestation with a triplet pregnancy. Her past medical history included post-streptococcal glomerulonephritis at the age of nine and, as a result, chronic bilateral renal failure. She underwent right kidney transplantation 10 years later, and since then she has been treated with cyclosporin (100 mg32 / day), azathioprine (100 mg31 / day) and prednisone (5 mg31 / day). Her past gynecological history included olygomenorrhea and secondary infertility. She had an early spontaneous abortion 5 years prior to her admission. Previous fertility investigation revealed anovulation, and she was diagnosed as suffering from polycystic ovarian syndrome. She conceived following induction of ovulation using 31 ampoules of human menopausal gonadotropins (HMG). An ultrasound examination confirmed the presence of three viable intrauterine fetuses. A multidisciplinary consulting team comprising a nephrologist, a transplantation surgeon and a perinatologist was called for recommendations on her clinical management. The major concern was to determine the degree of possible renal impairment concomitant with an increase in total plasma volume in triplet pregnancy. In addition, the risk of premature delivery and small for gestational age babies with poor perinatal outcome was explained in detail to the couple. In order to increase the survival chances for the fetuses and to reduce the risk of renal function impairment during pregnancy, we suggested that the couple reduce the triplet to a twin pregnancy. After appropriate informed consent fetal reduction was performed transabdominally, using potassium chloride solution. The next day ultrasound examination confirmed the viability of the two fetuses in two different gestational sacs. During the course of the pregnancy the patient’s plasma creatinine was 0.7 mg / dl, creatinine clearance test was 148 ml / min and blood pressure remained stable throughout the

pregnancy. Ultrasound examination at 35 weeks’ gestation revealed discordant twins and growth retarded fetuses with estimated fetal weights of 1500 and 2000 g. Both twins were in breech presentation. At 36 week of gestation a Cesarean section was performed. The first twin female weighed 1460 g, and the second was a male with a birthweight of 1910 g, the Apgar scores for the twins were 9 at 1 min and 10 at 5 min, respectively. The postoperative course was uneventful. The mother and both babies were discharged from the hospital after 5 days. Six months after delivery the woman is well with no sign of impairment of renal function.

3. Case 2 A 31-year-old primigravida was referred to our medical service at 8 weeks’ gestation with a twin pregnancy. Her past medical history revealed systemic lupus erythematosus at 10 years of age. Due to lupus nephritis, recurrent urinary tract infections and renal failure as a result, she underwent kidney transplantation at the age of 27. There was early graft rejection after the transplantation surgery, and kidney reimplantation was needed. The patient was treated with immunosuppression drugs consisting of a combination of daily azathioprine (100 mg / day), cyclosporin (150 mg / day) and prednisone (10 mg / day). In addition, calcium-channel blocker (Nifedipine 20 mg / day) was needed to control high blood pressure. Due to anovulation and a male factor, in vitro fertilization and embryo transfer were performed and resulted in biamniotic bichorionic twin pregnancy. At admission her blood pressure was 140 / 90–145 / 95 mm / Hg, hemoglobin levels were 9.6–10.1 g / l, blood chemistry revealed creatinine level of 1.3 mg / dl, creatinine clearance test was 65 ml / min. She had massive proteinuria of 5–6 g / 24 h and microalbuminuria 2073.6 mg / 24 h. Glucose tolerance test (OGTT) revealed three pathological values and was decoded as type IV due to steroid treatment. At this point it was clear that the patient did not meet the optimum criteria for consideration of pregnancy in renal transplant recipients. A multidisciplinary consulting team was involved in this case management and the option of fetal reduction to a singleton was considered. After appropriate consulting, the couple decided to continue the pregnancy without any intervention. The patient was followed-up in high-risk pregnancy unit and no deterioration of renal function test, proteinuria or hypertension was noted. At 33 weeks’ gestation she was hospitalized for increased blood pressure levels to a value of 180 / 110 mm / Hg. Ultrasound examination revealed concordant twins with estimated fetal weights of 1680 and 1730 g. The patient was treated with intravenous magnesium sulfate (4-g loading dose and 2-g maintenance dose) and hydralasine (10 mg i.v.). A Cesarean section was performed 2

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days after her admission because of uncontrolled hypertension. Two healthy boys were delivered – the first in breech and second in vertex presentation, weighing 1540 and 1658 g with Apgar scores of 8 at 1 min and 10 at 5 min, respectively, with cord pH of 7.16 and 7.18. Both of the neonates were healthy and no respiratory distress syndrome was noted. The postoperative course was uneventful and the mother with both her children were discharged from the hospital 10 days following the surgery.

4. Discussion Nowadays, more and more women in the reproductive age group undergo successful renal transplantation. Therefore, the number of pregnancies in renal allograft recipients can be expected to increase. Women suffering from chronic renal failure usually present with anovulatory cycles and infertility [4]. The frequency of multiple pregnancies in those women appears to be increased partially due to widespread use of induction of ovulation and assisted reproductive techniques. Managing these patients with multiple pregnancies after renal transplantation creates obstetrical dilemmas. The outcome of singleton pregnancy in women after renal transplantation can be expected to be favorable; 60–70% of the offspring will have an uncomplicated neonatal course [4–6]. Sciarra et al. reported a favorable outcome for one set of twins (6%) in a series of 17 pregnancies [7]. Both twins delivered vaginally at 38 weeks’ gestation with no maternal or fetal complications. Four sets of twins (3%) and one set of triplets (1%) were reported by the European Dialysis and Transplantation Association among 120 successful pregnancies after renal transplantation [8]. Recently, two case reports documented successful twin and triplet pregnancies in renal transplant recipients [9,10]. Our report is consistent with the limited data in the literature that women with a renal transplant can have a successful pregnancy but there are definite risks for both mother and fetus. The medical problems occurring during multiple pregnancies in transplant recipients are undoubtedly of great concern. Prematurity is often a complication. Therefore, the possibility of fetal reduction is very attractive in order to reduce the risk of preterm labor and delivery. In 1993, Evans et al. reported collaborative experience of transabdominal reduction from six medical centers around the world. The success rate of fetal reduction was 100% and 75 of 463 patients (16.2%) lost their entire pregnancy prior to 24 weeks’ gestation [11]. Other report suggests that the pregnancy lost rate from transabdominal multifetal pregnancy reduction procedures is at the rate of 8–9% [12]. There seems to be no doubt today that quadruplet and higher order pregnancies are appropriate candidates to

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benefit from multifetal pregnancy reduction [13,14]. Recent studies suggest that the benefits of reducing triplets to twins exceed the risks involved in the procedure. Lipitz et al. reported that a loss of the entire pregnancy occurred in 20.7% of the triplet pregnancies managed expectantly compared to 8.7% in the group with reduction to twins [15]. It is abundantly clear that pregnancy loss is not the only poor outcome. The other important issue of concern is very early premature delivery. In addition, prematurity among renal transplanted patients by itself, has been reported to range from 43 to 53% [1,2]. In some cases this has resulted from early termination of pregnancy due to preeclampsia. Indeed, both our patients delivered prematurely, one at 36 weeks of gestation and the other at 33 weeks because of severe preeclampsia. Based on the existing obstetric data we decided to perform fetal reduction from triplets to a twin pregnancy in one of our patients. We originally thought that leaving only one fetus would generally be a poor medical decision, because of the risk of losing the entire pregnancy. There are no data in the literature regarding recommendations for fetal reduction in patients suffering from significant medical conditions like renal transplantation, except for a few sporadic cases such as severe cardiac diseases [16]. Therefore, we decided on a reduction of only one fetus, from triplets to twins in the first patient. Indeed, there were no medical complications during pregnancy and she delivered normal healthy babies at 36 weeks of gestation. The second patient presented severe medical complications including chronic hypertension, renal function impairment and recurrent episodes of urinary tract infections. She had early graft rejection and reimplantation before the current pregnancy, and her prenatal care revealed severe proteinuria and uncontrolled hypertension from the first trimester. This patient did not meet the optimum criteria for consideration of pregnancy in renal transplant recipients. These criteria include serum creatinine less than 2 mg / dl, well controlled hypertension, minimal or no proteinuria, immunosuppressive therapy 15 mg / day or less of prednisone and 2 mg / kg / day or less of azathioprine [3]. Indeed, severe hypertension, massive proteinuria, anemia and diabetes mellitus complicated her pregnancy and prenatal course. Twins pregnancy was diagnosed in the first trimester, creating an additional management dilemma. A medical and ethical decision of fetal reduction to singleton was raised in order to improve the maternal and perinatal outcome. After consulting, the couple refused to reduce the number of fetuses. Antepartum management required serial assessment of renal function, blood pressure control and treatment of recurrent urinary tract infection. The patient was hospitalized at 28 weeks of gestation and she was operated for uncontrolled preeclampsia and twins gestation at 33 weeks. In both of our patients preeclampsia or superimposed chronic hypertension was the indication for delivery. The

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literature uniformly supports an increased incidence of pregnancy induced hypertension (PIH) in 26–30% in renal transplantation patients [1,2,17]. This may sometimes be difficult to diagnose, because hypertension, proteinuria and edema may occur during these pregnancies without the presence of PIH. In addition, multiple pregnancy itself is a risk factor for the early appearance of preeclampsia. The incidence of preeclampsia in patients with a combination of renal transplant and multiple pregnancy is expected to be very high. The management of this complication should not differ from that in non-transplant patients, and iatrogenic problems introduced by the use of unnecessary drugs are to be avoided. When preeclampsia is severe, the therapeutic regiment of choice is delivery regardless of gestational age. Although preeclampsia, preterm delivery and deterioration of renal function complicated the prenatal courses of both of our patients, they delivered normal healthy babies and no adverse maternal outcome was observed. We do not know how a reduction to singleton pregnancy may have affected the pregnancy outcome in these cases. In the first case where the patient met the optimal criteria for consideration of pregnancy in renal transplant recipient, the pregnancy outcome was favorable. The second patient, who did not follow these criteria, pregnancy was terminated prematurely, though normal babies were born. Therefore, one can conclude that twin pregnancy in renal transplant patients can be expected to be favorable. However, high order multiple gestation should be reduced according to the current literature recommendation in healthy women. In summary, a combination of multifetal gestation in renal allograft recipient represents a high-risk pregnancy that should be managed at a tertiary care institution. The overall outcome in properly consulted patients can be considered favorable. Based on our limited experience with two cases, we suggest reduction of triplets to twin pregnancy in consistent with the current literature data. Although the ethical issue associated with multifetal reduction procedures is complex, we believe that patients with renal transplant should be offered this therapeutic option in cases of triplet pregnancies.

5. Condensation Multifetal gestation in renal allograft recipient represents a high risk pregnancy that should be managed at a tertiary

care institution. We recommend reduction of triplets to twin pregnancy in consistency with the current literature data.

References [1] Fine RN. Pregnancy in renal allograft recipients. Am J Nephrol 1982;2:117. [2] Davidson JM, Lindheimer MD. Pregnancy in renal transplant patient. J Reprod Med 1982;27:613. [3] Penn I, Makowski EL, Harris P. Parenthood following renal transplantation. Kidney Int 1980;18:221. [4] Lau RJ, Scott JR. Pregnancy following renal transplantation. Clin Obstet Gynecol 1985;28:339. [5] Blowey DL, Warady BA. Neonatal outcome in pregnancies associated with renal replacement therapy. Adv Ren Replace Ther 1998;5:45–52. [6] Armenti VT, Moritz MJ, Davison JM. Medical management of the pregnant transplant recipients. Adv Ren Replace Ther 1998;5:14– 23. [7] Sciarra JJ, Toledo-Pereyra LH, Bendell RP, Simmons RL. Pregnancy following renal transplantation. Am J Obstet Gynecol 1975;123:411. [8] European Dialysis and Transplant Association. Successful pregnancies in women treated by dialysis and kidney transplantation. Br J Obstet Gynaecol 1980; 87: 839–845. [9] Prieto C, Errasti P, Olaizola JI, et al. Successful twin pregnancies in renal transplant recipients taking cyclosporine. Transplantation 1989;48:1065–7. [10] Jimenez E, Gonzales-Caraballo Z, Morales-Otero L, et al. Triplets born to a kidney transplant recipient. Transplantation 1995;59:435– 6. [11] Evans MI, Dommergues M, Warpner RJ, et al. Efficacy of transabdominal multifetal pregnancy reduction: collaborative experience among world’s largest centers. Obstet Gynecol 1993;82:61. [12] Evans MI, Dommergues M, Timor-Trisch, et al. Transabdominal versus transcervical and transvaginal multifetal pregnancy reduction: international collaborative experience of more than one thousand cases. Am J Obstet Gynecol 1994;170:799. [13] Berkowitz RL, Lynch L, Chitkara U, et al. Selective reduction of multifetal pregnancies in the first trimester. New Engl J Med 1988;318:1043. [14] Lipitz M, Mashiach S, Seidman DS. Multifetal pregnancy reduction: The case for non-directive patients counceling. Hum Reprod 1994;9:1978. [15] Lipitz M, Reichman BN, Uval J, et al. A prospective comparison of the outcome of triplet pregnancies managed expectantly or by multifetal reduction to twins. Am J Obstet Gynecol 1994;170:874. [16] Evans MI, Littman L, Richter R, et al. Selective reduction for multifetal pregnancy: Early opinion revisited. J Reprod Med 1997;42:771. [17] Scott JR. Gynecologic and obstetric problems in renal allograft recipients: In: Buchbaum HV, Schmidt J, editors. Gynecologic urology. Second edition, Philadelphia: WB Saunders, 1982:547.