Bourdon, M. 1 , Santulli, P. 1 , Maignein, C. 1 , Gayet, V. 1 , Marcellin, L. 1 , Blanchet, V. 1 , Gonnot, J. 1 , Chapron, C. 1 1 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique – Hôpitaux de Paris (AP HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and ReproducMve Medicine, 75679 Paris, France ART outcomes for fresh versus deferred frozenthawed day2 embryo transfer: a matched cohort study Mathilde Bourdon
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Bourdon, M.1, Santulli, P. 1, Maignein, C.1 , Gayet, V.1, Marcellin, L.1, Blanchet, V.1, Gonnot, J.1, Chapron, C. 1
1 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique – Hôpitaux de Paris (AP-‐ HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics
II and ReproducMve Medicine, 75679 Paris, France
ART outcomes for fresh versus deferred frozen-‐thawed day-‐2 embryo transfer:
a matched cohort study
Mathilde Bourdon
Weinerman. R and Mainigi. M, FS., 2014
Gene expression profiles of simulated and nonsLmulated human endometrium during the window of embryo implantaLon
Adverse impact of COS on endometrial recepLvity ?
Bourgain C.and Devroey P., HR, 2003
“freeze-‐all” strategy
-‐> The hypothesis is that introducMon of a frozen-‐thawed-‐embryo into a potenMally more favorable intrauterine environment could avoid possible adverse
impact of COS on endometrial recepMvity.
cryopreservaMon of all viable embryos aXer COS, with transfer of a frozen-‐thawed embryo in a subsequent cycle
Vitrified-warmed blastocyst transfer cycles yieldhigher pregnancy and implantation rates comparedwith fresh blastocyst transfer cycles—time for a newembryo transfer strategy?
a IVF Program, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Jiangsu, People’s Republic of China;b Nanyang Technological University, Singapore; and c IVF Program, Shanghai 1st Maternity and Infant Hospital, TongjiUniversity, Shanghai, People’s Republic of China
Objective: To compare the clinical outcome of fresh versus vitrified-warmed blastocyst transfer (BT) cycles.Design: Retrospective study.Setting: Medical university affiliated hospital.Patient(s): Women aged less than 40 years undergoing BT cycles.Intervention(s): Vitrification and warming of blastocyst with the Cryotop system.Main Outcome Measure(s): Clinical pregnancy rate (CPR), implantation rate (IR), and multiple pregnancy rate(MPR).Result(s): In 110 fresh BT cycles versus 136 vitrified-warmed BT cycles performed from January 2007 to March2010, the IR and CPR of vitrified-warmed BT cycles were 37.0% and 55.1%, respectively, which were statisticallysignificantly higher than the corresponding values of 25.2% and 36.4% obtained for fresh BT cycles. Additionally,the MPR was not statistically significantly different between vitrified-warmed and fresh BT cycles when a similarnumber of blastocysts was transferred to patients.Conclusion(s): Vitrified-warmed BT cycles resulted in statistically significantly higher CPR and IR compared withfresh BT cycles. A new embryo transfer strategy is therefore proposed whereby fresh BTwould be avoided in theinitial ovarian stimulation cycle. Instead, all the patient’s available blastocysts would be vitrified-warmed andtransferred in subsequent cycles. (Fertil Steril! 2011;95:1691–5. "2011 by American Society for ReproductiveMedicine.)
Blastocyst transfer (BT) is effective for enhancing implantation andclinical pregnancy rates, resulting in better clinical outcomes (1, 2).However, it is not always possible to perform fresh BT cycles forevery patient with in vitro fertilization/intracytoplasmic sperminjection (IVF-ICSI) embryos that have successfully been culturedup to the blastocyst stage. Occasionally, fresh BT cycles must becanceled for patients who have exhibited poor endometrialreceptivity or ovarian hyperstimulation syndrome. Under suchcircumstances, all available fresh blastocysts would be cryopreservedfor transfer in a subsequent cycle. Additionally, if there is failure inachieving pregnancy after initial transfer of fresh blastocysts, surpluscryopreserved blastocysts would be transferred in a subsequent cycle.
Vitrification is the preferred method of cryopreservation as op-posed to slow-freezing protocols, due to lack of ice crystallizationand convenience of the procedure itself (3, 4). Generally, it is
widely believed that fresh embryo transfer cycles yield betterclinical results than either frozen-thawed or vitrified-warmed em-bryo transfer cycles. The pertinent question that remains unan-swered is whether blastocyst vitrification compromises embryonicdevelopmental potential. We compared the implantation and clinicalpregnancy rates of fresh versus vitrified-warmed BT cycles.
MATERIALS AND METHODSPatientsFrom January 2007 to March 2010, we performed 136 vitrified-warmed BTcycles, in 48 patients undergoing ICSI treatment. During the same period, weperformed 110 fresh BT cycles, in 32 patients undergoing ICSI treatment.The two data sets were comparable as there were no statistically significantdifferences between the two groups in patient parameters such as age, dura-tion of infertility, etiology of infertility, or proportion of ICSI cycles (P>.05,Table 1). All patients in the control group had surplus vitrified blastocysts forfuture transfer. Hence, the data were not in any way skewed by the inherentlyhigher success rate of patients with excess embryos to cryopreserve ascompared with patients who had only fresh embryos for transfer.
Ovarian StimulationThe standard long protocol for ovarian stimulation was used for patients inthis study (5). Briefly, 0.1 mg SC of the gonadotropin-releasing hormone(GnRH) agonist triptorelin (Decapeptyl; Ipsen-Biotech Inc., Paris, France)was administered in the midluteal phase of the previous cycle, followed by
Received October 12, 2010; revised December 8, 2010; accepted January6, 2011; published online February 11, 2011.
D.Z. has nothing to disclose. J.Z. has nothing to disclose. S.C. has nothingto disclose. J.Z. has nothing to disclose. B.C.H. has nothing to disclose.M.H. has nothing to disclose. X.L. has nothing to disclose. T.D. hasnothing to disclose. G.Q.T. has nothing to disclose.
Reprint requests: Guo Qing Tong, M.D., Ph.D., Director, Department ofAssisted Reproductive Technology, Shanghai 1st Maternity and InfantHospital of Tongji University, Changle Road 536, Shanghai, People’sRepublic of China 200040 (E-mail: [email protected]).
0015-0282/$36.00 Fertility and Sterility# Vol. 95, No. 5, April 2011 1691doi:10.1016/j.fertnstert.2011.01.022 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
ARTICLE
Freeze-all can be a superior therapy toanother fresh cycle in patients with priorfresh blastocyst implantation failure
Bruce S. Shapiro a,b,*, Said T. Daneshmand a,b, Forest C. Garner a,b,Martha Aguirre a, Cynthia Hudson a
a Fertility Center of Las Vegas, Las Vegas, NV, USA; b Department of Obstetrics and Gynecology, School of Medicine,University of Nevada, Las Vegas, NV, USA* Corresponding author. E-mail address: [email protected] (BS Shapiro).
Dr Shapiro earned his MD from the University of Nevada, Reno, and his PhD from the University of Amsterdam.He completed his residency in obstetrics and gynaecology and his fellowship in reproduction endocrinology atYale-New Haven Hospital. He is chief of the Division of Reproductive Endocrinology and Infertility in the Uni-versity of Nevada School of Medicine’s Department of Obstetrics and Gynecology. He is also a high-complexitylaboratory director. He is the founder and medical director of the Fertility Center of Las Vegas. His recent re-search has included endometrial receptivity, embryo cryopreservation and alternative ovulatory triggeringtechniques.
Please cite this article in press as: Bruce S. Shapiro, Said T. Daneshmand, Forest C. Garner, Martha Aguirre, Cynthia Hudson, Freeze-all is a superior therapy toanother fresh cycle in patients with prior fresh blastocyst implantation failure, Reproductive BioMedicine Online (2014), doi: 10.1016/j.rbmo.2014.04.009
www.sciencedirect .comwww.rbmonl ine.com
Freeze all Cleavage stage embryo transfer
Roque,et al. FS, 2015
DAY-‐2 ET to freeze or not to freeze?
?
fresh day-‐2 embryo transfer (ET) deferred frozen-‐thawed day-‐2 embryo transfer (def-‐ET)
ART outcomes
10/2012 12/2014
A"er the first ET: ü Clinical PR ü Ongoing PR ü ImplantaMon rate
Number of oocytes retrieved 6.84 ± 3.42 7.90 ± 4.52 <0.001t
Number of mature oocytes retrieved
5.43 ± 2.60 6.20 ± 3.55 <0.001t
Number of 2PN embryos 3.41 ± 1.58 3.56 ± 1.72 NS
FerLlizaLon rate 68.08±25.40 66.00±27.24 NS
ART-‐characterisLcs
Fresh (n=325) Def-‐ET (n=325) P value Survival rate NA 92.9% NA Mean number of embryos transfer 1.77 ± 0.44 1.72 ± 0.47 NS Total number of embryos transferred
* embryos were morphologically assessed according to Consensus scoring system for cleavage-‐stage embryos (Alpha ScienMsts in ReproducMve Medicine and ESHRE Special Interest Group of Embryology, 2011)
PaLent’s Age at IVF (years) 0.92 0.88-‐0.97 0.001
BMI (kg/m2) 0.94 0.89-‐0.99 0.030
Number of 2PN embryos 1.19 1.04-‐1.40 0.010
≥ 1 embryo grade 1* transferred
1.97 1.26-‐3.05 0.003
Independent predictors for ongoing pregnancy mulLple logisLc regression analysis
Age Number of previous IVF cycles BMI AMH levels total dose of injected gonadotropin type of protocol number of 2PN transfer of at least one embryo grade 1
PotenMal confounding factors for ongoing pregnancy found to be staMsMcally significant at the threshold of p ≤ 0.10 in univariate analysis were tested in a mulMple logisMc regression model.
• ART outcomes were not improved by a deferred day-‐2 ET as compared to
a fresh day-‐2 ET • This provided us an overall view of the impact of day-‐2 deferred ET on
ART outcomes regardless of the indicaLons for the deferred transfers.
• Further invesMgaMons may be required to determine for which specific subgroups the “freeze -‐ all strategy” may be most efficient for ensuring increased-‐pregnancy rates
• Randomized controlled studies seems necessary to confirm theses results
Conclusion
Gynecology Surgical unit: C Chapron, B Borghese, P Santulli,
H Foulot, MC Lafay-Pillet, A Bourret, G Pierre, M Even, MC Lamau, L Marcellin, P Marzouk, Medical unit: A Gompel, G Plu-Bureau, L Maitrot
Reproductive Endocrinology unit: D de Ziegler, P Santulli, V Gayet, C Maignien, FX Aubriot
Intestinal surgery B Dousset, S Gaujoux, M Leconte
Radiology AE Millischer, L Maitrot
Laboratory: Genetic D Vaiman, F Mondon, S Barbaux
Laboratory: Imunulogy
F Batteux, S Chouzenoux C Nicco, C Chéreau, B Weill
Laboratory: Reproductive biology
JP Wolf, V Lange, K Pocate, JM Kuntzman, C Chalas
Statistical unit
F Goffinet, PY Ancel, C Prunet
D. de Ziegler, Professor and Head, Reproductive Endocrinology and Infertility unit, A. Gompel, Professor and Head, Medical Gynecological unit,
C. Chapron, Professor and Chair, Gynecology Obstetrics II and Reproductive Medicine