The aim of this study was to assess the progression of pain symptoms during assisted reproductive technology (ART) cycles following administration of GnRH agonist (GnRHa) versus human chorionic gonadotrophin (hCG) triggering.
Design:
Observational cohort study.
Setting:
A tertiary care university hospital in France.
Population:
Patients who underwent ART programs.
Methods:
Between January 01, 2014, and June 31, 2014, 122 cycles were allocated to 2 groups: GnRHa triggering with a scheduled differed embryo transfer (n = 57) or hCG triggering with a fresh embryo transfer (n = 70). Pelvic pain scores were evaluated using a visual analog scale (VAS) with regard to dysmenorrhea, dyspareunia, noncyclic pelvic pain, gastrointestinal, and lower urinary tract pain. The total VAS score was defined as the sum of the scores for the various symptoms. Evaluations were carried out twice: during the synchronization treatment prior to ovarian stimulation and during a final evaluation 3 weeks postretrieval. The data were processed using univariate and multivariate logistic regression models.
Main Outcome Measures:
Trends for total VAS change (ie, final VAS score − synchronization VAS score).
Results:
For both groups, pain increased during the ART procedure. Trends for the total VAS change revealed that the increase in pain was significantly less in the “GnRHa triggering” group compared to the “hCG triggering” group (3.77 ± 7.73 and 6.50 ± 6.57, P < .05, respectively). Multivariate logistic regression indicated that GnRHa triggering was associated with less of an increase in pain compared to hCG triggering (odds ratio = 0.31, 95% confidence interval 0.13-0.71, P < .05).
Conclusion:
Compared to hCG, GnRHa triggering limits pain symptom progression in the period immediately after ART.
KupkaMSFerrarettiAPde MouzonJ. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE. Hum Reprod. 2014;29(10):2099–2113. doi:10.1093/humrep/deu175.
2.
YoussefMAFMVan der VeenFAl-InanyHG. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014;(10):CD008046. doi:10.1002/14651858.
3.
DamewoodMDShenWZacurHASchlaffWDRockJAWallachEE. Disappearance of exogenously administered human chorionic gonadotropin. Fertil Steril. 1989;52(3):398–400.
4.
DelvigneARozenbergS. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8(6):559–577.
5.
RodewaldMHerrDDuncanWC. Molecular mechanisms of ovarian hyperstimulation syndrome: paracrine reduction of endothelial claudin 5 by hCG in vitro is associated with increased endothelial permeability. Hum Reprod Oxf Engl. 2009;24(5):1191–1199. doi:10.1093/humrep/den479.
6.
FatemiHMGarcia-VelascoJ. Avoiding ovarian hyperstimulation syndrome with the use of gonadotropin-releasing hormone agonist trigger. Fertil Steril. 2015;103(4):870–873. doi:10.1016/j.fertnstert.2015.02.004.
7.
BodriDGuillénJJTrullenqueMSchwennKEsteveCCollO. Early ovarian hyperstimulation syndrome is completely prevented by gonadotropin releasing-hormone agonist triggering in high-risk oocyte donor cycles: a prospective, luteal-phase follow-up study. Fertil Steril. 2010;93(7):2418–2420. doi:10.1016/j.fertnstert.2009.08.036.
8.
CasperRF. Reducing the risk of OHSS by GnRH agonist triggering. J Clin Endocrinol Metab. 2015:jc20153676. doi:10.1210/jc.2015-3676.
LoutradiKEKolibianakisEMVenetisCA. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008;90(1):186–193. doi:10.1016/j.fertnstert.2007.06.010.
11.
AbdelHafezFFDesaiNAbou-SettaAMFalconeTGoldfarbJ. Slow freezing, vitrification and ultra-rapid freezing of human embryos: a systematic review and meta-analysis. Reprod Biomed Online. 2010;20(2):209–222. doi:10.1016/j.rbmo.2009.11.013.
12.
ManzanaresMAGómez-PalomaresJLRicciarelliEHernándezER. Triggering ovulation with gonadotropin-releasing hormone agonist in in vitro fertilization patients with polycystic ovaries does not cause ovarian hyperstimulation syndrome despite very high estradiol levels. Fertil Steril. 2010;93(4):1215–1219. doi:10.1016/j.fertnstert.2008.12.019.
13.
KhanKNKitajimaMHirakiK. Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy. Hum Reprod Oxf Engl. 2010;25(3):642–653. doi:10.1093/humrep/dep437.
14.
KhanKNKitajimaMHirakiK. Cell proliferation effect of GnRH agonist on pathological lesions of women with endometriosis, adenomyosis and uterine myoma. Hum Reprod Oxf Engl. 2010;25(11):2878–2890. doi:10.1093/humrep/deq240.
15.
PrenticeADearyAJGoldbeck-WoodSFarquharCSmithSK. WITHDRAWN: Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 1999;(2):CD000346. doi:10.1002/14651858.
16.
Bayoglu TekinYDilbazBAltinbasSKDilbazS. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Fertil Steril. 2011;95(2):492–496. doi:10.1016/j.fertnstert.2010.08.042.
17.
SantulliPBourdonMPresseM. Endometriosis-related infertility: assisted reproductive technology has no adverse impact on pain or quality-of-life scores. Fertil Steril. 2016;105(4):978–987.e4. doi:10.1016/j.fertnstert.2015.12.006.
18.
LudwigAKGlawatzMGriesingerGDiedrichKLudwigM. Perioperative and post-operative complications of transvaginal ultrasound-guided oocyte retrieval: prospective study of >1000 oocyte retrievals. Hum Reprod Oxf Engl. 2006;21(12):3235–3240. doi:10.1093/humrep/del278.
19.
CerrilloMRodríguezSMayoralMPachecoAMartínez-SalazarJGarcia-VelascoJA. Differential regulation of VEGF after final oocyte maturation with GnRH agonist versus hCG: a rationale for OHSS reduction. Fertil Steril. 2009;91(4 suppl):1526–1528. doi:10.1016/j.fertnstert.2008.08.118.
20.
Garcia-VelascoJAMottaLLópezAMayoralMCerrilloMPachecoA. Low-dose human chorionic gonadotropin versus estradiol/progesterone luteal phase support in gonadotropin-releasing hormone agonist-triggered assisted reproductive technique cycles: understanding a new approach. Fertil Steril. 2010;94(7):2820–2823. doi:10.1016/j.fertnstert.2010.06.035.
21.
MarcouxSMaheuxRBérubéS. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337(4):217–222. doi:10.1056/NEJM199707243370401.
22.
AbraoMSGonçalves MO daCDiasJAPodgaecSChamieLPBlasbalgR. Comparison between clinical examination, transvaginal sonography and magnetic resonance imaging for the diagnosis of deep endometriosis. Hum Reprod Oxf Engl. 2007;22(12):3092–3097. doi:10.1093/humrep/dem187.
23.
PikettyMChopinNDoussetB. Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first-line imaging examination. Hum Reprod Oxf Engl. 2009;24(3):602–607. doi:10.1093/humrep/den405.
24.
KinkelKFreiKABalleyguierCChapronC. Diagnosis of endometriosis with imaging: a review. Eur Radiol. 2006;16(2):285–298. doi:10.1007/s00330-005-2882-y.
25.
ChapronCVieiraMChopinN. Accuracy of rectal endoscopic ultrasonography and magnetic resonance imaging in the diagnosis of rectal involvement for patients presenting with deeply infiltrating endometriosis. Ultrasound Obstet Gynecol. 2004;24(2):175–179. doi:10.1002/uog.1107.
26.
de ZieglerDGayetVAubriotFX. Use of oral contraceptives in women with endometriosis before assisted reproduction treatment improves outcomes. Fertil Steril. 2010;94(7):2796–2799. doi:10.1016/j.fertnstert.2010.05.056.
27.
SantulliPGayetVFauqueP. HIV-positive patients undertaking ART have longer infertility histories than age-matched control subjects. Fertil Steril. 2011;95(2):507–512. doi:10.1016/j.fertnstert.2010.09.018.
28.
ShapiroBSDaneshmandSTGarnerFCAguirreMHudsonCThomasS. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfers in high responders. Fertil Steril. 2011;96(2):516–518. doi:10.1016/j.fertnstert.2011.02.059.
MohamedAMFChouliarasSJonesCJPNardoLG. Live birth rate in fresh and frozen embryo transfer cycles in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2011;156(2):177–180. doi:10.1016/j.ejogrb.2011.01.020.
31.
ShapiroBSDaneshmandSTGarnerFCAguirreMHudsonC. Freeze-all can be a superior therapy to another fresh cycle in patients with prior fresh blastocyst implantation failure. Reprod Biomed Online. 2014;29(3):286–290. doi:10.1016/j.rbmo.2014.04.009.
32.
RovaKPassmarkHLindqvistPG. Venous thromboembolism in relation to in vitro fertilization: an approach to determining the incidence and increase in risk in successful cycles. Fertil Steril. 2012;97(1):95–100. doi:10.1016/j.fertnstert.2011.10.038.
ChapronCSantulliPde ZieglerD. Ovarian endometrioma: severe pelvic pain is associated with deeply infiltrating endometriosis. Hum Reprod Oxf Engl. 2012;27(3):702–711. doi:10.1093/humrep/der462.
35.
FauconnierAChapronCDubuissonJBVieiraMDoussetBBréartG. Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis. Fertil Steril. 2002;78(4):719–726.
36.
DoussetBLeconteMBorgheseB. Complete surgery for low rectal endometriosis: long-term results of a 100-case prospective study. Ann Surg. 2010;251(5):887–895. doi:10.1097/SLA.0b013e3181d9722d.
37.
BourdelNAlvesJPickeringGRamiloIRomanHCanisM. Systematic review of endometriosis pain assessment: how to choose a scale?Hum Reprod Update. 2015;21(1):136–152. doi:10.1093/humupd/dmu046.
38.
GejervallA-LStener-VictorinECerneABorgKBerghC. Pain aspects in oocyte aspiration for IVF. Reprod Biomed Online. 2007;14(2):184–190.
39.
BenagliaLSomiglianaESantiGScarduelliCRagniGFedeleL. IVF and endometriosis-related symptom progression: insights from a prospective study. Hum Reprod Oxf Engl. 2011;26(9):2368–2372. doi:10.1093/humrep/der208.
40.
HaasJOphirLBarzilayE. GnRH agonist vs. hCG for triggering of ovulation--differential effects on gene expression in human granulosa cells. PLoS One. 2014;9(3):e90359. doi:10.1371/journal.pone.0090359.
41.
HumaidanPKolSPapanikolaouE; Copenhagen GnRH Agonist Triggering Workshop Group. GnRH agonist for triggering of final oocyte maturation: time for a change of practice?Hum Reprod Update. 2011;17(4):510–524. doi:10.1093/humupd/dmr008.
42.
EngmannLBenadivaCHumaidanP. GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: a SWOT analysis. Reprod Biomed Online. 2016;32(3):274–285. doi:10.1016/j.rbmo.2015.12.007.
43.
VerhaakCMSmeenkJMEversAWKremerJAKraaimaatFWBraatDD. Women’s emotional adjustment to IVF: a systematic review of 25 years of research. Hum Reprod Update. 2007;13(1):27–36. doi:10.1093/humupd/dml040.
44.
Jongbloed-PereboomMMiddelburgKJHeinemanMJBosAFHaadsmaMLHadders-AlgraM. The impact of IVF/ICSI on parental well-being and anxiety 1 year after childbirth. Hum Reprod Oxf Engl. 2012;27(8):2389–2395. doi:10.1093/humrep/des163.
45.
GameiroSBoivinJPeronaceLVerhaakCM. Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment. Hum Reprod Update. 2012;18(6):652–669. doi:10.1093/humupd/dms031.
46.
LandJACourtarDAEversJL. Patient dropout in an assisted reproductive technology program: implications for pregnancy rates. Fertil Steril. 1997;68(2):278–281.
47.
Kiykac AltinbasSBayoglu TekinYDilbazBDilbazS. Evaluation of quality of life in fertile Turkish women with severe endometriosis. J Obstet Gynaecol. 2015;35(1):49–52. doi:10.3109/01443615.2014.930110.
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