Gynaecology

Risk Factors for Ectopic Pregnancy After In Vitro Fertilization Treatment

Mohammed Malak, MD, Tawfeeq Tawfeeq, MD, Hananel Holzer, MD, Togas Tulandi, MD, MHCM
Department of Obstetrics and Gynecology, McGill University, Montreal QC

Abstract
Objective: To identify risk factors for ectopic pregnancy after in vitro fertilization treatment. Methods: We conducted a study among women who conceived after IVF treatment and evaluated the possible risk factors for ectopic pregnancy. The parameters evaluated were demographics of the patients, cause of infertility, and risk factors for ectopic pregnancy, including tubal infertility and previous ectopic pregnancy. Results: Of 365 women, 18 women had an ectopic pregnancy and 347 others had an intrauterine pregnancy (control group). The incidence of IVF ectopic pregnancy was 4.9%. The mean age was 34.2 1.4 years in the ectopic group and 34.3 0.2 years in the control group; mean BMI was 23.8 1.0 in the ectopic group and 24.5 0.9 in the control group. Previous ectopic pregnancy, previous IVF ectopic pregnancy, or smoking did not affect the occurrence of ectopic pregnancy in this population. Logistic regression analysis demonstrated that tubal factor infertility and previous surgery for endometriosis were risk factors for IVF ectopic pregnancy. Conclusion: Tubal factor infertility and previous surgery for endometriosis appear to be risk factors for ectopic pregnancy after IVF treatment. Other factors that usually contribute to spontaneous ectopic pregnancy, including previous ectopic pregnancy, pelvic infection, and smoking, were not risk factors for IVF ectopic pregnancy in our study.

dinfertilit et les facteurs de risque de grossesse ectopique (y compris linfertilit tubaire et les antcdents de grossesse ectopique). Rsultats: Chez 365femmes, 18 femmes prsentaient une grossesse ectopique et les 347autres prsentaient une grossesse intra-utrine (groupe tmoin). Lincidence de la grossesse ectopique la suite de la FIV tait de 4,9%. Lge moyen tait de 34,2 1,4ans au sein du groupe ectopique et de 34,3 0,2 ans au sein du groupe tmoin; lIMC moyen tait de 23,8 1,0 au sein du groupe ectopique et de 24,5 0,9 au sein du groupe tmoin. Les antcdents de grossesse ectopique, les antcdents de grossesse ectopique la suite de la FIV ou le tabagisme nont pas affect la survenue de la grossesse ectopique au sein de cette population. Lanalyse de rgression logistique a dmontr que linfertilit de nature tubaire et que les antcdents de chirurgie visant lendomtriose taient des facteurs de risque de grossesse ectopique la suite de la FIV. Conclusion: Linfertilit de nature tubaire et les antcdents de chirurgie visant lendomtriose semblent tre des facteurs de risque de grossesse ectopique la suite dun traitement de FIV. Dautres facteurs qui contribuent habituellement la grossesse ectopique spontane (dont les antcdents de grossesse ectopique, linfection pelvienne et le tabagisme) ne se sont pas avrs tre des facteurs de risque de grossesse ectopique la suite dun traitement de FIV dans le cadre de notre tude. J Obstet Gynaecol Can 2011;33(6):617619

Rsum
Objectif: Identifier les facteurs de risque de grossesse ectopique la suite dun traitement de fcondation in vitro. Mthodes: Nous avons men une tude auprs de femmes qui sont devenues enceintes la suite dun traitement de FIV et nous avons valu les facteurs de risque possibles en ce qui concerne la grossesse ectopique. Les paramtres valus taient les caractristiques dmographiques des patientes, la cause

INTRODUCTION

Key Words: Ectopic pregnancy, in vitro fertilization, IVF, risk factors Competing Interests: None declared. Received on January 5, 2011 Accepted on January 19, 2011

n vitro fertilization may be followed by ectopic pregnancy. The Canadian ART registry reported 51 ectopic pregnancies among 2499 clinical pregnancies (2%) after IVF/ICSI treatment.1 In the results generated from the American Society for Reproductive Medicine in 2001, there were 560 ectopic pregnancies, representing 1.8% of all pregnancies following IVF.2 These rates are comparable to the rate in the general population (19 per 1000 pregnancies).3 The purpose of our study was to evaluate risk factors associated with ectopic pregnancy (tubal infertility, previous ectopic pregnancy, PID, smoking, and previous surgery for endometriosis or myomectomy) among women who conceived with IVF treatment.

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Gynaecology

Table 1. Median antral follicle count and basal serum hormone levels among women with ectopic pregnancy and intrauterine pregnancy after IVF treatment
Pregnancy Ectopic (n =18) Intrauterine (n = 347) Antral follicle count 9 (7 to 18) 14 (9 to 21) FSH (IU/L) 6.8 (6.1 to 9.0) 7.8 (6.5 to 9.6) LH (IU/L) 4.9 (3.9 to 6.7) 4.5 (3.2 to 6.2) Estradiol (nmol/L) 143.1 (86 to 225) 141.5 (106 to 203)

Data are presented as median (interquartile range)

Table 2. Possible risk factors for ectopic pregnancy after IVF treatment
Risk factor Tubal infertility Previous ectopic pregnancy Previous IVF ectopic pregnancy Smoking Pelvic infection Previous surgery for endometriosis Previous myomectomy Ectopic pregnancy n = 18 n (%) 6 (33.3) 3 (16.6) 1 (5.6) 1 (5.6) 1 (5.6) 4 (22.2) 1 (5.6) Intrauterine pregnancy n = 347 n (%) 26 (7.5) 29 (8.3) 12 (3.5) 33 (9.5) 13 (3.5) 11 (3.2) 6 (1.7) Odds ratio 3.99 0.93 0.65 0.55 0.91 5.16 4.39 95% CI 1.23 to 12.98 0.52 to 12.34 0.04 to 6.84 0.07 to 4.44 0.11 to 7.79 1.25 to 21.21 0.45 to 43.07 P 0.02 0.24 0.62 0.57 0.92 0.02 0.20

MATERIALS AND METHODS

RESULTS

We reviewed the medical records of 385 consecutive women who conceived after treatment with IVF at the McGill Reproductive Centre in Montreal from January 2003 to December 2008. Information was retrieved from the reproductive centres medical files. The parameters evaluated were patient demographics and risk factors for ectopic pregnancy, including tubal infertility, previous ectopic pregnancy, previous IVF ectopic pregnancy, and smoking. We also assessed the significance of a history of myomectomy (identified as a risk factor for IVF ectopic pregnancy in one study4) or surgery for endometriosis. We used the Shapiro Wilks test to evaluate the distribution of the data. Comparisons were analyzed using Student t test or Mann-Whitney U test when appropriate. Risk factors were evaluated using multiple logistic regression, and we calculated odds ratios with 95% confidence intervals. A P value of <0.05 was considered significant. Ethics approval for the study was provided by the McGill University Health Centre Research Ethics Board.

In this cohort, the incidence of IVF ectopic pregnancy was 4.9%. Of 18 ectopic pregnancies, one was a cornual pregnancy. The mean age in the ectopic group was 34.21.4 years and mean BMI was 23.81.0; in the control group, the mean age was 34.30.2 years and mean BMI was 24.50.9. The antral follicle count and basal serum levels of follicle stimulating hormone, luteinizing hormone, and estradiol in each group are shown in Table 1. The median number of embryos transferred was the same in each group. Logistic regression analysis demonstrated that tubal factor infertility and previous surgery for endometriosis were risk factors for IVF ectopic pregnancy (Table 2).
DISCUSSION

ABBREVIATIONS

ART assisted reproductive technology ICSI intracytoplasmic sperm injection PID pelvic inflammatory disease

The incidence of IVF ectopic pregnancy varies from 1.8% to 11% among those with tubal factor infertility.15 In our study, one third of the patients with ectopic pregnancy had tubal factor infertility. This might explain the high incidence of ectopic pregnancy in our cohort. Tubal factor infertility has been shown by Strandell et al. to be one of the risk factors for ectopic pregnancy among women treated with IVF.4 In fact, these authors reported an incidence of ectopic pregnancy of 4%, similar to the rate in our population.

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Risk Factors for Ectopic Pregnancy After In Vitro Fertilization Treatment

Another risk factor for ectopic pregnancy that we identified was previous surgery for endometriosis. This risk could be attributed to the presence of peritubal adhesions that might impair tubal function in similar fashion to intrinsic tubal disease. It should be noted also that we cannot exclude the possibility of a type 2 statistical error. Previous myomectomy has been identified as a risk factor for IVF ectopic pregnancy in one study, 4 although in that study there were only three patients with a previous myomectomy among women with ectopic pregnancy. We encountered only one patient with a previous myomectomy, and could not confirm a correlation with ectopic pregnancy. Obviously, both studies had insufficient statistical power to demonstrate any relationship between previous myomectomy and ectopic pregnancy. A risk factor for ectopic pregnancy in general is previous ectopic pregnancy.68 In our study, neither this factor nor a history of pelvic infection or smoking appeared to correlate with IVF ectopic pregnancy. Reports from individual institutions on these possible risk factors have been mixed.9,10 In our study, a history of pelvic infection was identified through the history taken from couples during their infertility assessment. We distinguished pelvic inflammatory disease or sexually transmitted disease from lower genital tract infection such as monilial vaginitis. It is possible that patients might not have volunteered having had a previous pelvic infection, or the infection could have been subclinical. This could explain why there was no apparent increase in EP in those women. A weakness of our study is the relatively small number of women with ectopic pregnancy. However, our findings support previous reports that tubal infertility is a risk factor. Accordingly, one should consider the possibility of ectopic pregnancy among women who conceive with IVF treatment, especially in those with tubal factor infertility.

CONCLUSION

Tubal infertility and previous surgery for endometriosis appear to be risk factors for ectopic pregnancy after IVF treatment. Other factors that usually contribute to the risk of ectopic pregnancy in general, such as a previous ectopic pregnancy, a history of pelvic infection, and smoking, were not found to be risk factors for ectopic pregnancy after IVF treatment in this series.
REFERENCES
1. Gunby J, Bissonnette F, Librach C, Cowan L; IVF Directors Group of the Canadian Fertility and Andrology Society. Assisted reproductive technologies (ART) in Canada: 2004 results from the Canadian ART Register. Fertil Steril 2008;89:112332. 2. Society for Assisted Reproductive Technology; American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 2001 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology registry. Fertil Steril 2007;87:125366. 3. Centers for Disease Control and Prevention. Ectopic pregnancy United States 1990-1992. MMWR Morb Mortal Wkly Rep 1995;44:468. 4. Strandell A, Thorburn J, Hamberger L. Risk factors for ectopic pregnancy in assisted reproduction. Fertil Steril 1999;71:2826. 5. Dubuisson JB, Aubriot F, Mathieu L, Foulot H, Mandelbrot L, Bouquet de Joliniere J. Risk factors for ectopic pregnancy in 556 pregnancies after in-vitro fertilization: implications for preventive management. Fertil Steril 1991;56:68690. 6. Murray H, Baakdah H, Bardell T, Tulandi T. Diagnosis and treatment of ectopic pregnancy. CMAJ 2005;173:90512. 7. Ankum WM, Mol BWJ, Van Der Veen F, Bossuyt PMM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996;65:10939. 8. Bouyer J, Coste J, Shojaei T, Pouly JL, Fernandez H, Gerbaud L, et al. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. Am J Epidemiol 2003;157:18594. 9. Rosman ER, Keegan DA, Krey L, Liu M, Licciardi F, Grifo JA. Ectopic pregnancy rates after in vitro fertilization: a look at the donor egg population. Fertil Steril 2009;92:17913. 10. Weigert M, Gruber D, Pernicka E, Bauer P, Feichtinger W. Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in in vitro fertilization-embryo transfer patients. J Assisted Reprod Genetics 2009;26:137.

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