Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2016

Open Access 01-12-2016 | Research

Ectopic pregnancy risk factors for ART patients undergoing the GnRH antagonist protocol: a retrospective study

Authors: A. Weiss, R. Beck-Fruchter, J. Golan, M. Lavee, Y. Geslevich, E. Shalev

Published in: Reproductive Biology and Endocrinology | Issue 1/2016

Login to get access

Abstract

Background

In-vitro fertilization is a known risk factor for ectopic pregnancies. We sought to establish the risk factors for ectopic pregnancy in GnRH antagonist cycles examining patient and stimulation parameters with an emphasis on ovulation trigger.

Methods

We conducted a retrospective, cohort study of 343 patients undergoing 380 assisted reproductive technology (ART) cycles with the GnRH antagonist protocol and achieving a clinical pregnancy from November 2010 through December 2015.

Results

Significant risk factors for ectopic pregnancy in the univariate analysis included prior Cesarean section (CS), endometriosis, mechanical factor infertility, longer stimulation, elevated estradiol and progesterone levels, GnRH agonist trigger, higher number of oocytes aspirated, and insemination technique. Independent risk factors for ectopic pregnancy in the multivariate analysis included GnRH agonist trigger, higher number of oocytes aspirated, insemination technique, and prior Cesarean section.

Conclusion

Excessive ovarian response, IVF (as opposed to ICSI), prior Cesarean section and GnRH agonist trigger were found to be independent risk factors for ectopic pregnancy. Caution should be exercised before incorporating the GnRH agonist trigger for indications other than preventing OHSS. When excessive ovarian response leads to utilization of GnRH agonist trigger, strategies for preventing ectopic pregnancy, such as a freeze all policy or blastocyst transfer, should be considered. Further studies should elucidate whether adjusting the luteal support can reduce the ectopic pregnancy risk.
Literature
1.
Steptoe PC, Edwards RG. Reimplantation of a human embryo with subsequent tubal pregnancy. Lancet. 1974;307:880–2.CrossRef
2.
3.
Keeping D, Harrison K, Sherrin D. Ectopic Pregnancy Contralateral to Unilateral GIFT. Aust N Z J Obstet Gynaecol. 1993;33:95–6.CrossRefPubMed
4.
Li C, Meng C-X, Zhao W-H, Lu H-Q, Shi W, Zhang J. Risk factors for ectopic pregnancy in women with planned pregnancy: a case–control study. Eur J Obstet Gynecol Reprod Biol. 2014;181C:176–82.CrossRef
5.
Weström L. Incidence, trends, and risks of ectopic pregnancy in a population of women. Br Med J. 1981;282(January):15–8.CrossRef
6.
Kamwendo F, Forslin L, Bodin L, Danielsson D. Epidemiology of ectopic pregnancy during a 28 year period and the role of pelvic inflammatory disease. Sex Transm Infect. 2000;76:28–32.CrossRefPubMedPubMedCentral
7.
Santos-Ribeiro S, Tournaye H, Polyzos NP. Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies. Hum Reprod. 2016;31:dev315.CrossRef
8.
Strandell A, Thorburn J, Hamberger L. Risk factors for ectopic pregnancy in assisted reproduction. Fertil Steril. 1999;71:282–6.CrossRefPubMed
9.
Marcus SF, Brinsden PR. Analysis of the incidence and risk factors associated with ectopic pregnancy following in-vitro fertilization and embryo transfer. Hum Reprod. 1995;10:199–203.CrossRefPubMed
10.
Pyrgiotis E, Sultan KM, Neal GS, Liu HC, Grifo JA, Rosenwaks Z. Ectopic pregnancies after in vitro fertilization and embryo transfer. J Assist Reprod Genet. 1994;11:79–84.CrossRefPubMed
11.
Ng EH, Yeung WS, So WW, Ho PC. An analysis of ectopic pregnancies following in vitro fertilisation treatment in a 10-year period. J Obstet Gynaecol. 1998;18:359–64.CrossRefPubMed
12.
Decleer W, Osmanagaoglu K, Meganck G, Devroey P. Slightly lower incidence of ectopic pregnancies in frozen embryo transfer cycles versus fresh in vitro fertilization-embryo transfer cycles: a retrospective cohort study. Fertil Steril. 2014;101:162–5.CrossRefPubMed
13.
Smith LP, Oskowitz SP, Dodge LE, Hacker MR. Risk of ectopic pregnancy following day-5 embryo transfer compared with day-3 transfer. Reprod Biomed Online. 2013;27:407–13.CrossRefPubMed
14.
Clayton HB, Schieve LA, Peterson HB, Jamieson DJ, Reynolds MA, Wright VC. Ectopic pregnancy risk with assisted reproductive technology procedures. Obstet Gynecol. 2006;107:595–604.CrossRefPubMed
15.
Huang B, Ph D, Hu D, Qian K, Ph D, Ai J, Ph D, Li Y, Ph D, Jin L, Ph D. Is frozen embryo transfer cycle associated with a signi fi cantly lower incidence of ectopic pregnancy ? An. Fertil Steril. 2013;102:1345–9.CrossRef
16.
Londra L, Moreau C, Strobino D, Garcia J, Zacur H, Zhao Y. Ectopic pregnancy after in vitro fertilization: differences between fresh and frozen-thawed cycles. Fertil Steril. 2015;104:110–8.CrossRefPubMed
17.
Fang C, Huang R, Wei LN, Jia L. Frozen-thawed day 5 blastocyst transfer is associated with a lower risk of ectopic pregnancy than day 3 transfer and fresh transfer. Fertility and sterility. 2015;103:655–61.CrossRefPubMed
18.
Ankum WM, Mol BW, Van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril. 1996;65:1093–9.PubMed
19.
Audebert A, Pouly JL, Bonifacie B, Yazbeck C. Laparoscopic surgery for distal tubal occlusions: lessons learned from a historical series of 434 cases. Fertil Steril. 2014;1977:1203.CrossRef
20.
Hjordt Hansen MV, Dalsgaard T, Hartwell D, Skovlund CW, Lidegaard O. Reproductive prognosis in endometriosis. A national cohort study. Acta Obstet Gynecol Scand. 2014;93:483–9.CrossRefPubMed
21.
O’Neill SM, Agerbo E, Kenny LC, Henriksen TB, Kearney PM, Greene RA, Mortensen PB, Khashan AS. Cesarean section and rate of subsequent stillbirth, miscarriage, and ectopic pregnancy: a Danish register-based cohort study. PLoS Med. 2014;11, e1001670.CrossRefPubMedPubMedCentral
22.
Wu Z, Li R, Ma Y, Deng B, Zhang X, Meng Y, Chen X, Liu P, Qiao J. Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles. Reprod Biomed Online. 2012;24:511–20.CrossRefPubMed
23.
Wang J, Wei Y, Diao F, Cui Y, Mao Y, Wang W, Liu J. The association between polycystic ovary syndrome and ectopic pregnancy after in vitro fertilization and embryo transfer. Am J Obstet Gynecol. 2013;209:139.PubMed
24.
Lavy G, DeCherney AH. The hormonal basis of ectopic pregnancy. Clin Obstet Gynecol. 1987;30:217–24.CrossRefPubMed
25.
Sahin S, Ozay A, Ergin E, Turkgeldi L, Kürüm E, Ozornek H. The risk of ectopic pregnancy following GnRH agonist triggering compared with hCG triggering in GnRH antagonist ivf cycles. Arch Gynecol Obstet. 2014.
26.
Sousa M, Cunha M, Teixeira Da Silva J, Oliveira C, Silva J, Viana P, Barros A. Ovarian hyperstimulation syndrome: a clinical report on 4894 consecutive ART treatment cycles. Reprod Biol Endocrinol. 2015;13:66.CrossRefPubMedPubMedCentral
27.
Shapiro BS, Andersen CY. Major drawbacks and additional benefits of agonist trigger—not ovarian hyperstimulation syndrome related. Fertil Steril. 2015;103:874–8.CrossRefPubMed
28.
Humaidan P, Polyzos NP. Human chorionic gonadotropin vs. gonadotropin-releasing hormone agonist trigger in assisted reproductive technology-“The king is dead, long live the king!”. Fertil Steril. 2014;102:339–41.CrossRefPubMed
29.
Humaidan P, Van Vaerenbergh I, Bourgain C, Alsbjerg B, Blockeel C, Schuit F, Van Lommel L, Devroey P, Fatemi H. Endometrial gene expression in the early luteal phase is impacted by mode of triggering final oocyte maturation in recFSH stimulated and GnRH antagonist co-treated IVF cycles. Hum Reprod. 2012;27:3259–72.CrossRefPubMed
30.
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16:231–45.CrossRefPubMed
31.
Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19:41–7.CrossRef
32.
Weiss A, Neril R, Geslevich J, Lavee M, Beck-Fruchter R, Golan J, Shalev E. Lag time from ovulation trigger to oocyte aspiration and oocyte maturity in assisted reproductive technology cycles: a retrospective study. Fertil Steril. 2014;102:419–23.CrossRefPubMed
33.
Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grøndahl ML, Westergaard L, Andersen CY. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005;20:1213–20.CrossRefPubMed
34.
Shalev E, Yarom I, Bustan M, Weiner E, Ben-Shlomo I. Transvaginal sonography as the ultimate diagnostic tool for the management of ectopic pregnancy: experience with 840 cases. Fertil Steril. 1998;69:62–5.CrossRefPubMed
35.
Condous G, Okaro E, Khalid A, Lu C, Van Huffel S, Timmerman D, Bourne T. The accuracy of transvaginal ultrasonography for the diagnosis of ectopic pregnancy prior to surgery. Hum Reprod. 2005;20:1404–9.CrossRefPubMed
36.
Beck-Fruchter R, Weiss A, Lavee M, Geslevich Y, Shalev E. Empty follicle syndrome: successful treatment in a recurrent case and review of the literature. Hum Reprod. 2012;27:1357–67.CrossRefPubMed
37.
Rombauts L, McMaster R, Motteram C, Fernando S. Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles. Hum Reprod. 2015;30(12):2846–52.PubMed
38.
39.
Kolibianakis E, Bourgain C. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial. Fertil Steril. 2002;78(5):1025–9.CrossRefPubMed
40.
Bourgain C, Ubaldi F, Tavaniotou A. Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation. Fertil Steril. 2002;78:237–44.CrossRefPubMed
41.
Kunz G, Noe M, Herbertz M, Leyendecker G. Uterine peristalsis during the follicular phase of the menstrual cycle: effects of oestrogen, antioestrogen and oxytocin. Hum Reprod Update. 1998;4:647–54.CrossRefPubMed
42.
Paltieli Y, Eibschitz IZU, Ziskind G, Ohel G, Silbermann M. High progesterone levels and Ciliary dysfunction — a possible cause of ectopic pregnancy. J Assist Reprod Genet. 2000;17(2):103–6.CrossRefPubMedPubMedCentral
43.
Trau HA, Brännström M, Curry TE, Duffy DM. Prostaglandin E2 and vascular endothelial growth factor a mediate angiogenesis of human ovarian follicular endothelial cells. Hum Reprod. 2016;31:dev320.CrossRef
44.
Felemban A, Sammour A, Tulandi T. Serum vascular endothelial growth factor as a possible marker for early ectopic pregnancy. Hum Reprod. 2002;17:490–2.CrossRefPubMed
45.
Daniel Y, Geva E, Lerner-Geva L, Eshed-Englender T, Gamzu R, Lessing JB, Bar-Am A, Amit A. Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker? Fertil Steril. 1999;72:1013–7.CrossRefPubMed
46.
Engmann L, Benadiva C. Ovarian hyperstimulation syndrome prevention strategies: luteal support strategies to optimize pregnancy success in cycles with gonadotropin-releasing hormone agonist ovulatory trigger. Semin Reprod Med. 2010;28:506–12.CrossRefPubMed
47.
Fauser BC, De Jong D, Olivennes F, Wramsby H, Tay C, Itskovitz-Eldor J, Van Hooren HG. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. J Clin Endocrinol Metab. 2002;87:709–15.CrossRefPubMed
48.
Itskovitz-Eldor J, Kol S, Mannaerts B. Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndro. Hum Reprod. 2000;15:1965–8.CrossRefPubMed
49.
Shalev E, Geslevich Y, Ben-Ami M. Induction of pre-ovulatory luteinizing hormone surge by gonadotrophin-releasing hormone agonist for women at risk for developing the ovarian hyperstimulation syndrome. Hum Reprod. 1994;9:417–9.PubMed
50.
Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective rando. Fertil Steril. 2008;89:84–91.CrossRefPubMed
51.
Seyhan A, Ata B, Polat M, Son W-Y, Yarali H, Dahan MH. Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG. Hum Reprod. 2013;28:2522–8.CrossRefPubMed
52.
Humaidan P, Ejdrup Bredkjær H, Westergaard LG, Yding Andersen C. 1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study. Fertil Steril. 2010;93:847–54.CrossRefPubMed
53.
54.
Refaat B, Dalton E, Ledger WL. Ectopic pregnancy secondary to in vitro fertilisation-embryo transfer: pathogenic mechanisms and management strategies. Reprod Biol Endocrinol. 2015;13:30.CrossRefPubMedPubMedCentral
55.
Pope C. Influence of embryo transfer depth on in vitro fertilization and embryo transfer outcomes. Fertil Steril. 2004;81:51–8.CrossRefPubMed
56.
Mains L, Van Voorhis BJ. Optimizing the technique of embryo transfer. Fertil Steril. 2010;94:785–90.CrossRefPubMed
57.
Krissi H, Hiersch L, Stolovitch N, Nitke S, Wiznitzer A, Peled Y. Outcome, complications and future fertility in women treated with uterine artery embolization and methotrexate for non-tubal ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol. 2014;182:172–6.CrossRefPubMed
58.
Frydman R, Nargund G. Mild approaches in assisted reproduction--better for the future? Fertil Steril. 2014;102:1540–1.CrossRefPubMed
59.
Griesinger G, Schultz L, Bauer T, Broessner A, Frambach T, Kissler S. Ovarian hyperstimulation syndrome prevention by gonadotropin-releasing hormone agonist triggering of final oocyte maturation in a gonadotropin-releasing hormone antagonist protocol in combination with a “freeze-all” strategy: a prospective multicentric st. Fertil Steril. 2011;95:2029–33. 2033.e1.CrossRefPubMed
60.
Herrero L, Pareja S, Losada C, Cobo AC, Pellicer A, Garcia-Velasco JA. Avoiding the use of human chorionic gonadotropin combined with oocyte vitrification and GnRH agonist triggering versus coasting: a new strategy to avoid ovarian hyperstimulation syndrome. Fertil Steril. 2011;95:1137–40.CrossRefPubMed
Metadata
Title
Ectopic pregnancy risk factors for ART patients undergoing the GnRH antagonist protocol: a retrospective study
Authors
A. Weiss
R. Beck-Fruchter
J. Golan
M. Lavee
Y. Geslevich
E. Shalev
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2016
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-016-0146-0

Other articles of this Issue 1/2016

Reproductive Biology and Endocrinology 1/2016 Go to the issue

Research

Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro

Research

Cryopreservation and xenografting of human ovarian fragments: medulla decreases the phosphatidylserine translocation rate

Research

ACTH-induced stress in weaned sows impairs LH receptor expression and steroidogenesis capacity in the ovary

Research

Osmotic-shock produced by vitrification solutions improves immature human oocytes in vitro maturation

Short Communication

Mutations in gonadotropin-releasing hormone signaling pathway in two nIHH patients with successful pregnancy outcomes

Review

Risk of adverse pregnancy and perinatal outcomes after high technology infertility treatment: a comprehensive systematic review