Similar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation

doi:10.1016/S1472-6483(10)60781-X

Reproductive BioMedicine Online

Volume 14, Issue 2, 2007, Pages 148-154

https://doi.org/10.1016/S1472-6483(10)60781-X Get rights and content

Abstract

The pregnancy rates after triggering of final oocyte maturation with gonadotrophin-releasing hormone (GnRH) agonist in GnRH-antagonist ovarian stimulation protocols are lower than those following triggering with human chorionic gonadotrophin (HCG). Furthermore, lower pregnancy rates following GnRH-antagonist protocols compared with long GnRH-agonist protocols have been reported. The differences might be due to an impact on oocyte number and quality or on the endometrium. If any stimulation protocol had a negative impact on oocyte quality, then further evidence of this effect would be observed following frozen–thawed embryo transfer originating from that stimulation cycle. The outcome of frozen–thawed embryo transfer was retrospectively analysed using the long protocol with triptorelin depot 3.75 mg (n = 215) or 0.1 mg/day (n = 83), or GnRH-antagonist protocol with either HCG (n = 69) or GnRH-agonist (n = 25) for final oocyte maturation. The outcomes measured were implantation rate, clinical pregnancy rate, ongoing pregnancy rate and embryo survival rate. All outcomes were similar in the four groups. It is concluded that the potential for frozen–thawed embryos to implant and develop following transfer is independent of the GnRH-analogue and the final oocyte maturation protocol used in the collection cycle. Lower IVF embryo transfer success using GnRH-antagonist/GnRH-agonist protocol does not appear to be related to an adverse effect on oocyte quality.

Section snippets

Dr Talia Eldar-Geva has been a senior physician in the IVF Unit at Shaare-Zedek Medical Center, Jerusalem, Israel, since 1999, when she returned from fellowship at Monash IVF, Melbourne, Australia. She obtained her MD and PhD degrees at the Hebrew University in Jerusalem. She is a Senior Lecturer in Obstetrics and Gynecology and Reproductive Medicine in Ben-Gurion University of the Negev. Her main research interests are focused on prognostic factors for IVF outcome, PCOS and reproductive

References (38)

B Asimakopoulos et al.
Outcome of cryopreserved pronuclear oocytes obtained after ovarian stimulation with either HMG or recFSH and the GnRH-antagonist cetrorelix
Reproductive Biomedicine Online
(2002)
A Gabrielsen et al.
Parameters predicting the implantation rate of thawed IVF/ICSI embryos: a retrospective study
Reproductive BioMedicine Online
(2006)
Y Hu et al.
Maximizing pregnancy rates and limiting higher-order multiple conceptions by determining the optimal number of embryos to transfer based on quality
Fertility and Sterility
(1998)
D Loutradis et al.
A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol
Fertility and Sterility
(2004)
O Nevo et al.
Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin
Fertility and Sterility
(2003)
N Nikolettos et al.
Comparison of cryopreservation outcome with human pronuclear stage oocytes obtained by the GnRH antagonist, cetrorelix, and GnRH agonists
European Journal of Obstetrics, Gynecology and Reproductive Biology
(2000)
S Oehninger et al.
Impact of different clinical variables on pregnancy outcome following embryo cryopreservation
Molecular and Cellular Endocrinology
(2000)
P Saadat et al.
Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone agonists versus antagonists
Fertility and Sterility
(2004)
AS Seelig et al.
Comparison of cryopreservation outcome with gonadotropin-releasing hormone agonists or antagonists in the collecting cycle
Fertility and Sterility
(2002)
JJ Stachecki et al.
Cryopreservation of biopsied cleavage stage human embryos
Reproductive Biomedicine Online
(2005)

BC Tarlatzis et al.

Direct ovarian effects and safety aspects of GnRH agonists and antagonists

Reproductive BioMedicine Online

(2002)

K Zikopoulos et al.

Duration of gonadotropin-releasing hormone antagonist administration does not affect the outcome of subsequent frozen–thawed cycles

Fertility and Sterility

(2004)

C Albano et al.

Controlled ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the LHRH-antagonist Cetrorelix (Cetrotide) and the LHRH-agonist Buserelin

Human Reproduction

(2000)

H Al-Inany et al.

GnRH antagonist in assisted reproduction: a Cochrane review

Human Reproduction

(2002)

R Babayof et al.

Serum inhibin A, VEGF and TNFαlevels after triggering oocyte maturation with GnRH-agonist compared to hCG in women with polycystic ovaries undergoing IVF treatment: a prospective randomized trial

Human Reproduction

(2006)

NG Beckers et al.

Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment

Journal of Clinical Endocrinology and Metabolism

(2003)

D Bodri et al.

Comparison between a GnRH antagonist and a GnRH agonist flare-up protocol in oocyte donors: a randomized clinical trial

Human Reproduction

(2006)

BC Fauser et al.

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

The Journal of Clinical Endocrinology and Metabolism

(2002)

RE Felberbaum et al.

Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages

Journal of Assisted Reproduction and Genetics

(1996)

Cited by (44)

Does the interval between the last GnRH antagonist dose and the GnRH agonist trigger affect oocyte recovery and maturation rates?
2020, Reproductive BioMedicine Online
Does the time interval between the last gonadotrophin-releasing hormone (GnRH) antagonist dose and the GnRH agonist trigger affect the efficacy of the trigger in IVF treatments?
This retrospective cohort study involved 53 normogonadotrophic patients undergoing GnRH antagonist-based IVF cycles, in a single academic centre between June 2019 and February 2020, in whom a GnRH agonist was used for final ovulation triggering.
The mean time interval between the last GnRH antagonist dose and GnRH agonist triggering was 4.6 ± 2.7 h (range 1–12 h). There was no correlation between the antagonist–agonist interval and the oocyte recovery rate (Spearman's correlation coefficient [CC] 0.02, P = 0.89) or metaphase II oocyte rate (CC 0.006, P = 0.96). On multivariate analysis, the antagonist–agonist interval was not associated with treatment outcomes, after adjusting for the women's age and body mass index.
This is the first study assessing the efficacy of the GnRH agonist trigger in relation to the time interval between the last GnRH antagonist dose and the agonist trigger within the first half-life of the GnRH antagonist and in less than 12 h. In normogonadotrophic patients, a GnRH agonist trigger can successfully induce an effective LH surge and oocyte maturation and release, irrespective of the time interval between the last antagonist dose and the agonist trigger. Once confirmed by randomized clinical trials, these finding may simplify treatment, improve patients’ convenience and promote patient adherence to treatment.
Euploidy rates between cycles triggered with gonadotropin-releasing hormone agonist and human chorionic gonadotropin
2019, Fertility and Sterility
Citation Excerpt :
Last, we report on euploidy rates as the primary outcome, and this ultimately needs to be correlated with clinical outcome data. No difference in pregnancy rates was appreciated among our patients who underwent an FET, and prior studies evaluating frozen transfer outcomes after GnRHa vs. hCG trigger have demonstrated similar pregnancy outcomes among groups, further substantiating our results (16–18). In conclusion, this study demonstrates that during IVF, euploidy rates per embryo biopsied and per oocyte retrieved are unaffected by GnRHa trigger compared with hCG.
To evaluate differences in euploidy rates between IVF cycles triggered with either GnRH agonist (GnRHa) or hCG.
Retrospective cohort study.
University-affiliated fertility center.
A total of 366 patients performing 539 IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A).
Gonadotropin-releasing hormone agonist or hCG trigger of oocyte maturation during IVF cycles.
Rate of euploid embryos.
Patients in the GnRHa trigger arm were younger, with a lower body mass index and higher antimüllerian hormone level, and they had a higher number of oocytes retrieved and embryos biopsied. Euploid rate per embryo biopsied was higher after GnRHa trigger than after hCG trigger (37.8% ± 2.1% vs. 30.3% ± 1.8%), but multivariate regression analysis controlling for potential confounding factors did not show any differences between the two groups. Moreover, the euploid rate per oocyte retrieved was not significantly different overall (GnRHa vs. hCG: 33.9% ± 2.2% vs. 28.0% ± 1.9%). The anticipated decline in the rate of euploid embryos per oocyte retrieved went from 15.8% ± 1.2% for age <35 years to 4.3% ± 0.9% for patients aged ≥41 years. There were no significant differences between the two groups after stratifying by age and controlling for PGT-A testing modality.
Both GnRHa and hCG trigger result in comparable euploid rates. Trigger with GnRHa should therefore be considered a valid option for trigger modality in freeze-all PGT-A cycles, in view of its demonstrated effectiveness and known safety enhancement.
Tasas de euploidía entre ciclos con inducción de maduración ovocitaria con agonista de hormona liberadora de gonadotropina y con gonadotropina coriónica humana
Evaluar las diferencias en las tasas de euploidía entre ciclos de FIV inducidos con agonista de GnRH (GnRHa) o con hCG.
Estudio retrospectivo de cohortes.
Centro de fertilidad universitario.
Un total de 366 pacientes que realizaron 539 ciclos de FIV utilizando diagnóstico genético preimplantacional de aneuploidías (PGT-A).
Inducción de la maduración ovocitaria con agonista de hormona liberadora de gonadotropina o con hCG durante ciclos de FIV.
Tasa de embriones euploides.
Las pacientes en el grupo de inducción con GnRHa eran más jóvenes, con un menor índice de masa corporal y mayor nivel de hormona antimülleriana y tuvieron más ovocitos y más embriones biopsiados. La tasa de euploidía por embrión biopsiado fue mayor tras inducción con GnRHa que con hCG (37.8% ± 2.1% vs. 30.3% ± 1.8%), pero el análisis de regresión multivariable controlando los potenciales factores de confusión no mostró diferencia alguna entre ambos grupos. Además, la tasa de euploidía por ovocito obtenido no fue globalmente diferente de manera significativa (GnRHa vs. hCG: 33.9% ± 2.2% vs. 28.0% ± 1.9%). El descenso esperado en la tasa de embriones euploides por ovocito obtenido fue de 15.8% ± 1.2% en mujeres menores de 35 años a 4.3% ± 0.9% en mujeres de 41 años o mayores. No hubo diferencias significativas entre ambos grupos tras estratificar por edad y controlar la modalidad de PGT-A utilizada.
Tanto la inducción de maduración ovocitaria con GnRHa como con hCG resultan en tasas de euploidía comparables. Por tanto, la inducción con GnRHa debería considerarse como una modalidad válida para criopreservación en ciclos de PGT-A, a la vista de su demostrada eficacia y conocida mayor seguridad.
Cryopreserved embryo transfer: adjacent or non-adjacent to failed fresh long GnRH-agonist protocol IVF cycle
2017, Reproductive BioMedicine Online
Citation Excerpt :
According to the long down-regulation protocol at our unit, patients were administered at mid-luteal phase either triptorelin acetate continuous release 3.75 mg i.m. (decapeptyl C.R.; Ferring Ltd, Herzliya, Israel) or triptorelin acetate 0.1 mg/day s.c. (Ferring Ltd). Following pituitary suppression, recombinant FSH (rFSH)(Gonal-F; Serono, Herzliya, Israel) and human menopausal gonadotrophin (HMG) (Menogon; Ferring Ltd) were administered daily as previously described (Eldar-Geva et al., 2007). Oocyte retrieval was performed by ultrasound-guided follicle aspiration, 36–38 h after HCG administration.
The optimal time to perform cryopreserved embryo transfer (CET) after a failed oocyte retrieval-embryo transfer (OR-ET) cycle is unknown. Similar clinical pregnancy rates were recently reported in immediate and delayed CET, performed after failed fresh OR-ET, in cycles with the gonadotrophin-releasing hormone (GnRH) antagonist protocol. This study compared outcomes of CET performed adjacently (<50 days, n = 67) and non-adjacently (≥50 to 120 days, n = 62) to the last OR-day of cycles with the GnRH agonist down-regulation protocol. Additional inclusion criteria were patients' age 20–38 years, the transfer of only 1–2 cryopreserved embryos, one treatment cycle per patient and artificial preparation for CET. Significantly higher implantation, clinical pregnancy and live birth rates were found in the non-adjacent group than in the adjacent group: 30.5% versus 11.3% (P = 0.001), 41.9% versus 17.9% (P = 0.003) and 32.3% versus 13.4% (P = 0.01), respectively. These results support the postponement of CET after a failed OR-ET for at least one menstrual cycle, when a preceding long GnRH-agonist protocol is used.
GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: A SWOT analysis
2016, Reproductive BioMedicine Online
Gonadotrophin releasing hormone agonist (GnRHa) trigger is effective in the induction of oocyte maturation and prevention of ovarian hyperstimulation syndrome during IVF treatment. This trigger concept, however, results in early corpora lutea demise and consequently luteal phase dysfunction and impaired endometrial receptivity. The aim of this strenghths, weaknesses, opportunities and threats analysis was to summarize the progress made over the past 15 years to optimize ongoing pregnancy rates after GnRHa trigger. The advantages and potential drawbacks of this type of triggering are reviewed. The current approach to the management of GnRHa trigger in autologous cycles is based on the peak serum oestradiol level or follicle number and aims at a fresh embryo transfer or a segmentation approach with elective cryopreservation policy. We recommend intensive luteal support with transdermal oestradiol and intramuscular progesterone alone if peak serum oestradiol is 4000 or more pg/ml after GnRHa trigger or dual trigger with GnRHa and HCG 1000 IU if peak serum oestradiol is less than 4000 pg/mL. On the contrary, we recommend HCG 1500 IU 35 h after GnRHa trigger if there are less than 25 follicles, or freeze all oocytes or embryos if there are over 25 follicles.
GnRH agonist versus GnRH antagonist in ovarian stimulation: Has the ongoing debate resolved?
2014, Reproductive BioMedicine Online
Ovarian reserve and PGD treatment outcome in women with myotonic dystrophy
2014, Reproductive BioMedicine Online
Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. There are conflicting reports about its effect on female fertility. This study investigated ovarian reserve and IVF–preimplantation genetic diagnosis (PGD) outcome in women with DM1. A total of 21 women undergoing PGD for DM1 were compared with 21 age- and body mass index-matched women undergoing PGD for other diseases. Ovarian reserve markers, response to stimulation, embryo quality and clinical pregnancy and live birth rates were compared. Day-3 FSH concentration was higher, while anti-Müllerian hormone concentration and antral follicle count were lower in the DM1 group (median, range: 6.9 (1.8–11.3) versus 5.7 (1.5–10.7) IU/l; 0.9 (0.17–5.96) versus 2.68 (0.5–9.1) ng/ml; and 13 (0–63) versus 23 (8–40) follicles, respectively, all P < 0.05). Total FSH dose was higher (5200 versus 2250 IU, P = 0.004), while the numbers of oocytes retrieved (10 versus 16, P < 0.04) and metaphase-II oocytes (9 versus 12, P < 0.03) were lower in the DM1 group. The number of cycles with top-quality embryos and the clinical pregnancy rate were lower in the DM1 group. In conclusion, there is evidence of diminished ovarian reserve and less favourable IVF–PGD outcome in women with DM1.
Myotonic Dystrophy (DM) is the most common form of muscular dystrophy in adults. There is evidence of subfertility in males affected with the disease but conflicting reports about the effect of the disease on female fertility. The aim of our study was to investigate ovarian reserve and IVF–PGD results in women with DM. Twenty-one women undergoing preimplantation genetic diagnosis (PGD) treatment for DM were compared to 21 age- and BMI matched women undergoing PGD treatment for other diseases. The two groups were compared for antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) levels (the best known markers of ovarian reserve and fertility potential), ovarian response, embryo quality and pregnancy and live birth rates. AFC and the AMH levels were statistically significant lower in the DM group. Total medication dose needed for ovarian stimulation was higher, the number of oocytes and mature oocytes retrieved, and the number of cycles with top quality embryos were lower in the DM group compared to the controls. In conclusion, there is evidence of diminished ovarian reserve, and less favorable IVF-PGD outcome in women with DM. Therefore, we recommend advising these women about the possibility of early decreasing ovarian function in order to prevent any delay in reproductive planning.

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ArticleSimilar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation

Abstract

Section snippets

Reproductive Biomedicine Online

Reproductive BioMedicine Online

Fertility and Sterility

Fertility and Sterility

Fertility and Sterility

European Journal of Obstetrics, Gynecology and Reproductive Biology

Molecular and Cellular Endocrinology

Fertility and Sterility

Fertility and Sterility

Reproductive Biomedicine Online

Reproductive BioMedicine Online

Fertility and Sterility

Controlled ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the LHRH-antagonist Cetrorelix (Cetrotide) and the LHRH-agonist Buserelin

Human Reproduction

GnRH antagonist in assisted reproduction: a Cochrane review

Human Reproduction

Serum inhibin A, VEGF and TNFαlevels after triggering oocyte maturation with GnRH-agonist compared to hCG in women with polycystic ovaries undergoing IVF treatment: a prospective randomized trial

Human Reproduction

Journal of Clinical Endocrinology and Metabolism

Comparison between a GnRH antagonist and a GnRH agonist flare-up protocol in oocyte donors: a randomized clinical trial

Human Reproduction

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

The Journal of Clinical Endocrinology and Metabolism

Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages

Journal of Assisted Reproduction and Genetics

Article
Similar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation