Are all-freeze cycles & frozen-thawed embryo transfers improving IVF outcomes?

Transcription

1 Are all-freeze cycles & frozen-thawed embryo transfers improving IVF outcomes? Andrea Weghofer Foundation for Reproductive Medicine 2017 New York, November 16-19

2 Conflict of interest No relevant financial rela/onship to declare.

3 Pa0ent safety Lebenss0lmodifika0on Pregnancy poten0al

4 Ovarian Hyperstimulation Syndrome Early onset OHSS: Exogeneous hcg Late onset OHSS: Endogeneous hcg Ovary ajer COH VEGF per follicle (gene0c predisposi0on) Vascular permeability adapted from Smith et al, Obstet Gyn Int 2015

5 Original Article Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome Z.-J. Chen, Y. Shi, Y. Sun, B. Zhang, X. Liang, Y. Cao, J. Yang, J. Liu, D. Wei, N. Weng, L. Tian, C. Hao, D. Yang, F. Zhou, J. Shi, Y. Xu, J. Li, J. Yan, Y. Qin, H. Zhao, H. Zhang, and R.S. Legro Lower moderate or severe OHSS rates a;er frozen embryo transfer. [OHSS: 1.3% vs. 7.1%, RR & 95% CI: 0.19 ( ), p<0.001] Chen et al, NEJM 2016

6 Cochrane Database of Systematic Reviews Fresh versus frozen embryo transfers in assisted reproduction (Review) Wong KM, van Wely M, Mol F, Repping S, Mastenbroek S OHSS. Wong et al, Cochrane Database Syst Rev 2017

7 Does a freeze-all policy increase pregnancy rates?

8 Embryonic loss Implanta0on

9 Oocyte yield & cumulative live birth Cumulative live birth rate (%) Cumulative live birth rate and number of retrieved oocytes Antagonist Agonist > Months from randomisation Months from randomisation Figure 5 CLBRs, strati ed for number of retrieved oocytes in four groups 1 3, 4 9, and >15 oocytes. The results for the GnRH-antagonist Toftager et al, Hum Reprod 2017

10 Progesterone rise & endometrial receptivity

11 Progesterone rise & oocyte yield 8.4% Low responders Normal responders High responders n=1866 Griesinger et al, Fertil Steril 2013

12 Progesterone & pregnancy per transfer n=1866 Griesinger et al, Fertil Steril 2013

13 Original Article Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome Z.-J. Chen, Y. Shi, Y. Sun, B. Zhang, X. Liang, Y. Cao, J. Yang, J. Liu, D. Wei, N. Weng, L. Tian, C. Hao, D. Yang, F. Zhou, J. Shi, Y. Xu, J. Li, J. Yan, Y. Qin, H. Zhao, H. Zhang, and R.S. Legro Table 3. Live Birth, Pregnancy, and Pregnancy Loss.* Outcome Frozen-Embryo Transfer (N = 746) Fresh-Embryo Transfer (N = 762) Absolute Difference between Groups (95% CI) Rate Ratio in Frozen-Embryo Group (95% CI) Primary outcome: live birth no. (%) 368 (49.3) 320 (42.0) 7.3 (2.3 to 12.4) 1.17 (1.05 to 1.31) Secondary outcomes no. (%) Biochemical pregnancy 492 (66.0) 492 (64.6) 1.4 ( 3.4 to 6.2) 1.02 (0.95 to 1.10) 0.57 Clinical pregnancy 438 (58.7) 428 (56.2) 2.5 ( 2.4 to 7.5) 1.05 (0.96 to 1.14) 0.32 Ongoing pregnancy** 393 (52.7) 372 (48.8) 3.9 ( 1.1 to 8.9) 1.08 (0.98 to 1.19) 0.13 Pregnancy loss no./total no. (%) P Value Among biochemical pregnancies 108/492 (22.0) 161/492 (32.7) 10.8 ( 16.3 to 5.2) 0.67 (0.54 to 0.83) <0.001 Among clinical pregnancies 64/438 (14.6) 107/428 (25.0) 10.4 ( 15.7 to 5.1) 0.58 (0.44 to 0.77) <0.001 First trimester 42/438 (9.6) 56/428 (13.1) 3.5 ( 7.7 to 0.7) 0.73 (0.50 to 1.07) 0.10 Second trimester 22/438 (5.0) 51/428 (11.9) 6.9 ( 10.6 to 3.2) 0.42 (0.26 to 0.68) <0.001 * Plus minus values are means ±SD. Chen et al, NEJM 2016

14 Freeze-all: An approach suitable for everybody?

15 Fresh versus frozen embryo transfers in assisted reproduction (Review) Wong et al, Cochrane Database Syst Rev 2017

16 Donor cycles: Fresh vs. frozen transfer Outcome All cycles c Cancellation before retrieval/thaw d Cancellation before transfer Pregnancy Live birth Transfers only e Implantation Pregnancy Live birth e Cryopreserved oocyte a cycles (%) Fresh oocyte cycles (%) RR b 95% CI arr b 95% CI f f 0.74 f f f f 0.88 f f f f 0.87 f f f f f f f f Crawford et al, Fertil Steril 2017

17 Elective frozen transfer for everybody? TABLE 2 Risk of abnormal implantation. Composite Biochemical Ectopic/heterotopic Transfer First-trimester type Live birth Transfer type outcome pregnancy a pregnancy b pregnancy loss c Live birth Fresh blastocyst Reference Fresh blastocyst Reference Reference Reference Fresh non-blastocyst Reference 0.82 ( ) Reference Fresh non-blastocyst 1.22 ( ) 1.21 ( ) 1.04 ( ) 1.15 ( ) 0.82 ( ) Frozen blastocyst 0.73 ( ) Frozen blastocyst 1.36 ( ) 1.41 ( ) 0.48 ( ) 1.29 ( ) 0.73 ( ) Frozen non-blastocyst 1.57 ( ) 1.63 ( ) 0.67 ( ) Frozen 1.34 non-blastocyst ( ) ( ) ( ) nd cale nd cale nd cale Note: Values are OR (95% CI). Models are adjusted for patient age (at the time of oocyte retrieval), parity, number of embryos transferred, infertility diagnosis, and calendar year of treatment. n= Wang et al, Fertil Steril 2017

18 We can t change the wind, but we can adjust the sails. Aristotle