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The incidence of preeclampsia and eclampsia in parturients who conceived in an in vitro fertilization programme
International Congress Series 1271 (2004) 372 – 375
www.ics-elsevier.com
The incidence of preeclampsia and eclampsia in parturients who conceived in an in vitro fertilization programme D. Tabsh a,*, T. Vejnovic a, N. Radunovic b, B. Nikolov c a
Clinic of Gynecology and Obstetrics, Clinical Center Novi Sad, Branimira Cosica 37, Novi Sad, Serbia and Montenegro 21 000, Yugoslavia b Institute of Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, Yugoslavia c Clinic of Gynecology and Obstetrics, Clinical Center Kragujevac, Serbia and Montenegro, Yugoslavia
Abstract. Introduction: Mothers from the in vitro fertilization programme (IVF) are at a higher risk of developing pregnancy-induced hypertension (PIH). The aim of our study was to analyze the incidence of preeclampsia and eclampsia in mothers who conceived by IVF. Methods and patients: It was a 5-year study. Study subjects were 116 parturients from the IVF programme. The control group comprised of 27,551 mothers from the general population. We analyzed only mothers with singleton pregnancies. Results: There were 2.59% parturients from the IVF programme, and 0.45% from the control group, with diagnosis of preeclampsia. This lead to a statistically significant difference: v2 = 7.22; p < 0.01. Eclampsia occurred in 0.86% mothers who conceived with use of IVF, and 0.05% parturients from the control group, which failed to reach significance (v2 = 3.04; p>0.05). Discussion: Mothers from the IVF programme have more risk factors for pregnancy-induced hypertension (over 34 years of age, multiple gestation, polyhydramnios. etc.). New approaches revealed that there are some aspects of the IVF such as ovulation induction, laboratory environment, etc., which might be involved in the etiopathogenesis of preeclampsia. Conclusion: Parturients from the IVF programme are at a higher risk for preeclampsia, but not eclampsia, when compared to mothers from the general population. D 2004 Elsevier B.V. All rights reserved. Keywords: Fertilization in vitro; Preeclampsia; Eclampsia
1. Introduction The etiologies of preeclampsia and eclampsia, the most severe entities of pregnancyinduced hypertension (PIH), still remain uncertain. These diseases are called either as ‘‘diseases of theories’’—they surprise with their wide spectrum of causes, clinical signs, complications and short- and long-term effects. Preeclampsia is defined as a hypertensive disorder after 20 weeks of pregnancy, combined with proteinuria and/or edema, while * Corresponding author. Tel.: +381-21-420-811; fax: +381-21-421-862. E-mail address: [email protected] (D. Tabsh). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.05.101
D. Tabsh et al. / International Congress Series 1271 (2004) 372–375
373
eclampsia is the occurrence of convulsions and/or coma in association with the signs and symptoms of preeclampsia. The risk factors for PIH, preeclampsia and eclampsia are maternal age (under 20 and over 34), preexisting hypertension and renal diseases, diabetes mellitus, inadequate nutrition, obesity, primiparity, physical and emotional stress, male gender, ABO-incompatibility, multiple pregnancy, polyhydramnios, cold and humid climate, etc. According to many authors, women who conceived in an assisted reproductive programme are at a higher risk of developing PIH, preeclampsia and eclampsia [1,2]. Because mothers from the in vitro fertilization programme (IVF) are often primiparas over 34 years of age, and because IVF pregnancies are often multiple, with male gender babies and complicated by polyhydramnios, and also because ‘‘IVF mothers’’ often psychologically differ from mothers who conceived naturally, the aim of our study was to analize the incidence of preeclampsia and eclampsia in ‘‘IVF parturients’’. 2. Methods and patients We performed our investigation as a semi-prospective, semi-retrospective 5-year study (January 1st, 1998– December 31st, 2002) at the Clinic of Gynecology and Obstetrics in Novi Sad, Serbia and Montenegro. We used data from medical birth registries and patientsV histories, and prospective anamnestic data and clinical and laboratory examinations. We defined preeclampsia in labour as an increase in blood pressure to at least 140/90 mm Hg maximum 3 days before delivery, along with proteinuria (at least 0.3 g per 24 h). At the beginning of the research, we selected two groups of parturients—the first, control group, was population-based (women who had conceived by any of the assisted reproductive technique (ART)—standard in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) or intrauterine insemination were excluded). The second one, the study group, consisted of parturients who had become pregnant only in a standard IVF programme. We analyzed only women with singleton pregnancies. We recorded the number of mothers with diagnosis of preeclampsia and eclampsia in both groups. We also analyzed parturients within 24 h after labour. Women who entered labour with diagnosis of preeclampsia and developed eclampsia within 24 h after delivery were considered as cases of eclampsia. For analyzing the statistical significance we used a chi-square test. 3. Results From 1998 to 2002, there was a total of 116 singleton births resulting from a standard IVF (0.42% of all singleton births at the Clinic). The control group included 27 551 mothers, which is the number of parturients from the general population (without women who had conceived in an assisted reproductive programme or who had carried more than one baby). There were 3 (2.59%) parturients from the IVF programme, and 125 (0.45%) from the control group, with the diagnosis of preeclampsia in labour. This lead to a statistically significant difference: v2 = 7.22; p < 0.01 (Fig. 1). Eclampsia occurred in one mother (0.86%) who conceived with the use of IVF and 14 (0.05%) parturients from the control group, which failed to reach the significance (v2 = 3.04; p>0.05) (Fig. 2). For two out of three ‘‘IVF parturients’’ with preeclampsia, the indication for IVF programme had been unexplained infertility, and for the other it had been an ovulatory
374
D. Tabsh et al. / International Congress Series 1271 (2004) 372–375
Fig. 1. Distribution of preeclampsia in parturients from the control (general population) and study (IVF) groups in the period 1998 – 2002.
disorder. One women out of three, delivered preterm (36 gestational weeks). Mother from the IVF programme who developed eclampsia, had entered the programme because of unexplained infertility and delivered at 32 gestational weeks. 4. Discussion Our findings of 0.45% parturients from the general population with diagnosis of preeclampsia were similar to findings of other authors [3]. On the other hand, it is hard to define what the diagnosis of preeclampsia really means worldwide, because preeclampsia is often confused with PIH. The incidence of eclampsia in our general population was 0.05% and this is equal or very similar to many reports [4]. In their 10-year review, Pandian et al. [5] found about 0.3% eclampsia in women with unexplained infertility and who carried one baby. Authors who had found more preeclampsia or eclampsia in ‘‘IVF mothers’’ tried to explain this with well known risk
Fig. 2. Eclampsia in mothers from the control (general population) and study (IVF) groups in the period 1998 – 2002.
D. Tabsh et al. / International Congress Series 1271 (2004) 372–375
375
factors [2]. For example, primiparity is a known risk factor for preeclampsia or eclampsia [6] and mothers from the IVF programme are mainly primiparas (‘‘a disease of first pregnancy’’). But many controlled studies revealed some other risk factors for PIH in ‘‘IVF mothers’’. These factors are the unique characteristics of the IVF programme— beside indications for entering the programme, there are laboratory factors, ovulation induction, etc. Genbacev et al. [7] recently concluded that there is a very similar etiopathogenesis of preeclampsia and idiopathic infertility. The influence of the IVF laboratory on the future development of PIH is also possible, because in the pathogenesis of PIH the critical moment is the inadequate development of the early trophoblast. In an IVF programme, extraembryonic tissues are the ‘‘first line of defense’’ from mechanical and oxidative damages. Thompson et al. [8] reminded on environmentally induced cellular stress in an IVF laboratory. We conclude that there was a statistically significant difference in occurring preeclampsia, but not eclampsia, between mothers from IVF programme and parturients from general population. There was a higher incidence of preeclampsia in women who had conceived in an IVF programme. Future studies should be directed towards defining influences of every step of an IVF programme on the development of an early trophoblast. References [1] U. Lang, et al., Pregnancies after assisted reproduction—higher risk of adverse outcome, Am. J. Obstet. Gynecol. 185 (Suppl. 6) (2001) S101. [2] K. Fiedler, et al., Course of pregnancy and labor following in vitro fertilization. A retrospective study of 246 deliveries, Z. Geburtshilfe Perinatol. 194 (1) (1990) 8 – 12. [3] M. Sean Esplin, et al., Paternal and maternal components of the predisposition to preeclampsia, N. Engl. J. Med. 344 (12) (2001) 867 – 872. [4] K.A. Douglas, C.W.G. Redman, Eclampsia in the United Kingdom, BMJ 309 (1994) 1395 – 1400. [5] Z. Pandian, S. Bhattacharya, A. Templeton, Review of unexplained infertility and obstetric outcome: a 10 year review, Hum. Reprod. 16 (12) (2001) 2593 – 2597. [6] G.A. Dekker, B.M. Sibai, Etiology and pathogenesis of preeclampsia: current concepts, Am. J. Obstet. Gynecol. 179 (5) (1998) 1359 – 1375. [7] O.D. Genbacev, et al., Trophoblast L-selectin-mediated adhesion at the maternal – fetal interface, Science 299 (5605) (2003) 405 – 408. [8] J.G. Thompson, et al., Short- and long-term consequences for the health of children conceived through assisted reproduction technology: more reason for caution? Hum. Reprod. 17 (11) (2002) 2783 – 2786.
www.ics-elsevier.com
The incidence of preeclampsia and eclampsia in parturients who conceived in an in vitro fertilization programme D. Tabsh a,*, T. Vejnovic a, N. Radunovic b, B. Nikolov c a
Clinic of Gynecology and Obstetrics, Clinical Center Novi Sad, Branimira Cosica 37, Novi Sad, Serbia and Montenegro 21 000, Yugoslavia b Institute of Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, Yugoslavia c Clinic of Gynecology and Obstetrics, Clinical Center Kragujevac, Serbia and Montenegro, Yugoslavia
Abstract. Introduction: Mothers from the in vitro fertilization programme (IVF) are at a higher risk of developing pregnancy-induced hypertension (PIH). The aim of our study was to analyze the incidence of preeclampsia and eclampsia in mothers who conceived by IVF. Methods and patients: It was a 5-year study. Study subjects were 116 parturients from the IVF programme. The control group comprised of 27,551 mothers from the general population. We analyzed only mothers with singleton pregnancies. Results: There were 2.59% parturients from the IVF programme, and 0.45% from the control group, with diagnosis of preeclampsia. This lead to a statistically significant difference: v2 = 7.22; p < 0.01. Eclampsia occurred in 0.86% mothers who conceived with use of IVF, and 0.05% parturients from the control group, which failed to reach significance (v2 = 3.04; p>0.05). Discussion: Mothers from the IVF programme have more risk factors for pregnancy-induced hypertension (over 34 years of age, multiple gestation, polyhydramnios. etc.). New approaches revealed that there are some aspects of the IVF such as ovulation induction, laboratory environment, etc., which might be involved in the etiopathogenesis of preeclampsia. Conclusion: Parturients from the IVF programme are at a higher risk for preeclampsia, but not eclampsia, when compared to mothers from the general population. D 2004 Elsevier B.V. All rights reserved. Keywords: Fertilization in vitro; Preeclampsia; Eclampsia
1. Introduction The etiologies of preeclampsia and eclampsia, the most severe entities of pregnancyinduced hypertension (PIH), still remain uncertain. These diseases are called either as ‘‘diseases of theories’’—they surprise with their wide spectrum of causes, clinical signs, complications and short- and long-term effects. Preeclampsia is defined as a hypertensive disorder after 20 weeks of pregnancy, combined with proteinuria and/or edema, while * Corresponding author. Tel.: +381-21-420-811; fax: +381-21-421-862. E-mail address: [email protected] (D. Tabsh). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.05.101
D. Tabsh et al. / International Congress Series 1271 (2004) 372–375
373
eclampsia is the occurrence of convulsions and/or coma in association with the signs and symptoms of preeclampsia. The risk factors for PIH, preeclampsia and eclampsia are maternal age (under 20 and over 34), preexisting hypertension and renal diseases, diabetes mellitus, inadequate nutrition, obesity, primiparity, physical and emotional stress, male gender, ABO-incompatibility, multiple pregnancy, polyhydramnios, cold and humid climate, etc. According to many authors, women who conceived in an assisted reproductive programme are at a higher risk of developing PIH, preeclampsia and eclampsia [1,2]. Because mothers from the in vitro fertilization programme (IVF) are often primiparas over 34 years of age, and because IVF pregnancies are often multiple, with male gender babies and complicated by polyhydramnios, and also because ‘‘IVF mothers’’ often psychologically differ from mothers who conceived naturally, the aim of our study was to analize the incidence of preeclampsia and eclampsia in ‘‘IVF parturients’’. 2. Methods and patients We performed our investigation as a semi-prospective, semi-retrospective 5-year study (January 1st, 1998– December 31st, 2002) at the Clinic of Gynecology and Obstetrics in Novi Sad, Serbia and Montenegro. We used data from medical birth registries and patientsV histories, and prospective anamnestic data and clinical and laboratory examinations. We defined preeclampsia in labour as an increase in blood pressure to at least 140/90 mm Hg maximum 3 days before delivery, along with proteinuria (at least 0.3 g per 24 h). At the beginning of the research, we selected two groups of parturients—the first, control group, was population-based (women who had conceived by any of the assisted reproductive technique (ART)—standard in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) or intrauterine insemination were excluded). The second one, the study group, consisted of parturients who had become pregnant only in a standard IVF programme. We analyzed only women with singleton pregnancies. We recorded the number of mothers with diagnosis of preeclampsia and eclampsia in both groups. We also analyzed parturients within 24 h after labour. Women who entered labour with diagnosis of preeclampsia and developed eclampsia within 24 h after delivery were considered as cases of eclampsia. For analyzing the statistical significance we used a chi-square test. 3. Results From 1998 to 2002, there was a total of 116 singleton births resulting from a standard IVF (0.42% of all singleton births at the Clinic). The control group included 27 551 mothers, which is the number of parturients from the general population (without women who had conceived in an assisted reproductive programme or who had carried more than one baby). There were 3 (2.59%) parturients from the IVF programme, and 125 (0.45%) from the control group, with the diagnosis of preeclampsia in labour. This lead to a statistically significant difference: v2 = 7.22; p < 0.01 (Fig. 1). Eclampsia occurred in one mother (0.86%) who conceived with the use of IVF and 14 (0.05%) parturients from the control group, which failed to reach the significance (v2 = 3.04; p>0.05) (Fig. 2). For two out of three ‘‘IVF parturients’’ with preeclampsia, the indication for IVF programme had been unexplained infertility, and for the other it had been an ovulatory
374
D. Tabsh et al. / International Congress Series 1271 (2004) 372–375
Fig. 1. Distribution of preeclampsia in parturients from the control (general population) and study (IVF) groups in the period 1998 – 2002.
disorder. One women out of three, delivered preterm (36 gestational weeks). Mother from the IVF programme who developed eclampsia, had entered the programme because of unexplained infertility and delivered at 32 gestational weeks. 4. Discussion Our findings of 0.45% parturients from the general population with diagnosis of preeclampsia were similar to findings of other authors [3]. On the other hand, it is hard to define what the diagnosis of preeclampsia really means worldwide, because preeclampsia is often confused with PIH. The incidence of eclampsia in our general population was 0.05% and this is equal or very similar to many reports [4]. In their 10-year review, Pandian et al. [5] found about 0.3% eclampsia in women with unexplained infertility and who carried one baby. Authors who had found more preeclampsia or eclampsia in ‘‘IVF mothers’’ tried to explain this with well known risk
Fig. 2. Eclampsia in mothers from the control (general population) and study (IVF) groups in the period 1998 – 2002.
D. Tabsh et al. / International Congress Series 1271 (2004) 372–375
375
factors [2]. For example, primiparity is a known risk factor for preeclampsia or eclampsia [6] and mothers from the IVF programme are mainly primiparas (‘‘a disease of first pregnancy’’). But many controlled studies revealed some other risk factors for PIH in ‘‘IVF mothers’’. These factors are the unique characteristics of the IVF programme— beside indications for entering the programme, there are laboratory factors, ovulation induction, etc. Genbacev et al. [7] recently concluded that there is a very similar etiopathogenesis of preeclampsia and idiopathic infertility. The influence of the IVF laboratory on the future development of PIH is also possible, because in the pathogenesis of PIH the critical moment is the inadequate development of the early trophoblast. In an IVF programme, extraembryonic tissues are the ‘‘first line of defense’’ from mechanical and oxidative damages. Thompson et al. [8] reminded on environmentally induced cellular stress in an IVF laboratory. We conclude that there was a statistically significant difference in occurring preeclampsia, but not eclampsia, between mothers from IVF programme and parturients from general population. There was a higher incidence of preeclampsia in women who had conceived in an IVF programme. Future studies should be directed towards defining influences of every step of an IVF programme on the development of an early trophoblast. References [1] U. Lang, et al., Pregnancies after assisted reproduction—higher risk of adverse outcome, Am. J. Obstet. Gynecol. 185 (Suppl. 6) (2001) S101. [2] K. Fiedler, et al., Course of pregnancy and labor following in vitro fertilization. A retrospective study of 246 deliveries, Z. Geburtshilfe Perinatol. 194 (1) (1990) 8 – 12. [3] M. Sean Esplin, et al., Paternal and maternal components of the predisposition to preeclampsia, N. Engl. J. Med. 344 (12) (2001) 867 – 872. [4] K.A. Douglas, C.W.G. Redman, Eclampsia in the United Kingdom, BMJ 309 (1994) 1395 – 1400. [5] Z. Pandian, S. Bhattacharya, A. Templeton, Review of unexplained infertility and obstetric outcome: a 10 year review, Hum. Reprod. 16 (12) (2001) 2593 – 2597. [6] G.A. Dekker, B.M. Sibai, Etiology and pathogenesis of preeclampsia: current concepts, Am. J. Obstet. Gynecol. 179 (5) (1998) 1359 – 1375. [7] O.D. Genbacev, et al., Trophoblast L-selectin-mediated adhesion at the maternal – fetal interface, Science 299 (5605) (2003) 405 – 408. [8] J.G. Thompson, et al., Short- and long-term consequences for the health of children conceived through assisted reproduction technology: more reason for caution? Hum. Reprod. 17 (11) (2002) 2783 – 2786.