GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients

Humaıdan, Peter; Polyzos, Nikolaos P.; Alsbjerg, Birgit; Erb, Karin; Mikkelsen, A.-G.; Elbæk, Helle Olesen; Papanikolaou, Evangelos; Andersen, Claus Yding

doi:10.1093/humrep/det249

Cited by 188 publications

(190 citation statements)

References 41 publications

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“…Bunun yanında over stimulasyonunun etkisiyle yüksek estradiol seviyelerine bağlı ilişki sonrası daha uzun süre spermlerin servikal mukusda canlı kalabileceği literatürde bildirilmiştir (16) GnRH agonistlerinin tetiklediği LH artışı muhtemelen korpus luteum fonksiyonlarının devamını sağlamak için yeterli olmamaktadır. Bu nedenle düşük doz hCG, ya GnRH agonistleri ile beraber ya da oosit toplama işlemi öncesi uygulanabilir (15,17). Primatlarda pituiter gonadotropin desteği olmadan eksojen uygulanan LH desteğinin 3 gün içerisinde sağlanması ile corpus luteumun devam edebildiği görülmüştür (18).…”

Section: Discussionunclassified

GNRH Agoni̇st İle Teti̇kleme Sonrasi Tüm Embri̇yolarin Dondurulduğu Olguda Spontan Kli̇ni̇k Gebeli̇k / Spontaneous Clinical Pregnancy Following GNRH Agonist Triggering and Freeze All Policy

Olgan

Dırıcan

Erturk

2016

Osmangazi̇ Journal of Medicine

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ÖZET: Gonadotropin serbestleştirici hormon (GnRH) agonisti ile oosit matürasyonunun tetiklendiği ve sonrasında tüm embriyoların dondurulduğu 27 yaşındaki olguda luteal destek olmaksızın oluşan spontan klinik gebelik sunulmuştur. Polikistik over sendromu (PKOS) tanısıyla, öncesinde 3 sefer kontrollü ovaryan stimulasyon ve intrauterin inseminasyon uygulanmış olan hastaya GnRH antagonist protokolü ile intrasitoplasmik sperm enjeksiyonu tedavisi planlandı. Stimulasyonun 11. gününde ≥11 mm 25 adet folikül saptanması üzerine GnRH agonisti uygulanarak final oosit maturasyonu sağlandı. Blastokist evresine kadar gelişim gösteren yüksek kalitedeki embriyoların tümü vitrifiye edildi. Taze embriyo transferi planlanmaması dolayısıyla hastaya luteal faz desteği verilmeyerek yedi gün süreyle cinsel ilişki önerilmedi. Ancak, oosit toplanmasının 5 hafta sonrasında amenore yakınmasıyla tarafımıza tekrar başvuran hastaya yapılan transvajinal ultrasonografide fetal kalp atımı müspet spontan tekiz gebelik izlendi. Günümüzde, GnRH agonistlerle tetikleme sonrası luteal fazın nasıl desteklenmesi gerektiğine dair yoğun tartışmalar devam etmektedir. Bu bulgular, ovaryan stimulasyon sonrası suprafizyolojik steroid seviyelerine rağmen, her hastanın korpus luteum fonksiyonlarının devamının farklılık gösterebileceğine işaret etmektedir. Dolayısıyla, PKOS ve beraberinde endojen lüteinizan hormon aktivitesinin yüksek olduğu hastalar, korpus luteumun sınırlı ancak luteal faz için yeterli aktivitesinin devam edebileceği bir alt grubu oluşturuyor olabilir. ANAHTAR KELIMELER: GnRH agonist tetikleme, luteal faz desteği, spontan gebelik SPONTANEOUS CLINICAL PREGNANCY FOLLOWING GNRH AGONIST TRIGGERING AND FREEZE ALL POLICY ABSTRACT:We describe a 27 year-old patient undergoing follicle stimulation with gonadotrophin releasing hormone (GnRH) agonist and freeze-all approach, presented with spontaneous clinical pregnancy without supplementation of luteal phase. The patient had three attempts with controlled ovarian hyperstimulation and intrauterine insemination due to polycystic ovary syndrome (PCOS) before referring to our clinic for intracytoplasmic sperm injection. A GnRH antagonist protocol was assigned and ovarian stimulation commenced. After the detection of 25 follicles ≥11 mm, final oocyte maturation was triggered with GnRH agonist on the eleventh day of stimulation. Since freeze all approach was taken, no luteal phase support was administered. High quality blastocysts were vitrified. The couple was advised to refrain from sexual intercourse for seven days. The patient, however, presented with amenorrhea five weeks after the day of oocyte retrieval. A clinical pregnancy with fetal cardiac activity was determined on ultrasound examination. Currently, there is an ongoing debate on how best to counteract the negative impact of agonist triggering on the luteal phase. Our case demonstrates that corpus luteum functions might diverse despite supra-physiological sex steroids resulting from ovarian stimulation. Therefore, in case of PCOS consisting high e...

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Section: Discussionunclassified

GNRH Agoni̇st İle Teti̇kleme Sonrasi Tüm Embri̇yolarin Dondurulduğu Olguda Spontan Kli̇ni̇k Gebeli̇k / Spontaneous Clinical Pregnancy Following GNRH Agonist Triggering and Freeze All Policy

Olgan

Dırıcan

Erturk

2016

Osmangazi̇ Journal of Medicine

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“…The now wellestablished bolus dose of 1500 IU of hCG to stimulate CL function given at the time of OPU will result in hCG concentrations of around 30-50 IU/l tailing off to reach low concentrations around the mid-luteal phase. Administrating two bolus injections of 1500 IU (day OPU and day OPU + 5) in normally responding women [9] resulted in hCG levels around 40-60 IU/l during the mid-luteal phase, hence resulting in a slightly increased risk of OHSS (Fig. 4).…”

Section: Micro-dose Hcg Stimulation As Luteal Phase Support Mathematimentioning

confidence: 99%

“…In recent years, the GnRH agonist (GnRHa) trigger has been used as an alternative to the hCG trigger in patients following the antagonist protocol [7][8][9]. The GnRHa trigger Capsule It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…One important difference between the GnRHa trigger and the hCG bolus trigger is the effect on the early luteal phase [6,9]. In contrast to the hCG trigger, the GnRHa trigger is without stimulatory effect on the newly formed corpora lutea (CL).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to the hCG trigger, the GnRHa trigger is without stimulatory effect on the newly formed corpora lutea (CL). Thus, one pronounced characteristic of the GnRHa trigger is that it separates the two events traditionally undertaken by hCG, specifically induction of final follicular maturation and maintenance of the CL for early LPS [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience

Andersen

Fischer²,

Giorgione

et al. 2016

J Assist Reprod Genet

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For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the microdose hCG approach are presented.

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Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology

Youssef

Veen

Al-Inany

et al. 2014

Cochrane Database of Systematic Reviews

244

182

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GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients

Cited by 188 publications

References 41 publications

GNRH Agoni̇st İle Teti̇kleme Sonrasi Tüm Embri̇yolarin Dondurulduğu Olguda Spontan Kli̇ni̇k Gebeli̇k / Spontaneous Clinical Pregnancy Following GNRH Agonist Triggering and Freeze All Policy

GNRH Agoni̇st İle Teti̇kleme Sonrasi Tüm Embri̇yolarin Dondurulduğu Olguda Spontan Kli̇ni̇k Gebeli̇k / Spontaneous Clinical Pregnancy Following GNRH Agonist Triggering and Freeze All Policy

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience

Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology

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