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

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

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

Pa0ent safety Lebenss0lmodifika0on Pregnancy poten0al

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

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 (0.10-0.37), p<0.001] Chen et al, NEJM 2016

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

Does a freeze-all policy increase pregnancy rates?

Embryonic loss Implanta0on

Oocyte yield & cumulative live birth Cumulative live birth rate (%) 50 40 30 20 10 0 Cumulative live birth rate and number of retrieved oocytes Antagonist Agonist 1 3 4 9 10 15 >15 50 40 30 20 10 0 5 10 15 5 10 15 Months from randomisation Months from randomisation Figure 5 CLBRs, strati ed for number of retrieved oocytes in four groups 1 3, 4 9, 10 15 and >15 oocytes. The results for the GnRH-antagonist Toftager et al, Hum Reprod 2017

Progesterone rise & endometrial receptivity

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

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

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) 0.004 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

Freeze-all: An approach suitable for everybody?

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

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 3.9 4.4 0.89 0.60 1.31 0.89 0.60 1.31 8.5 11.5 0.74 f 0.57 0.96 f 0.74 f 0.57 0.96 f 51.1 58.5 0.87 f 0.81 0.95 f 0.88 f 0.81 0.95 f 43.0 49.4 0.87 f 0.79 0.95 f 0.87 f 0.80 0.95 f 39.9 49.0 0.81 f 0.73 0.91 f 0.99 0.89 1.09 55.9 66.1 0.85 f 0.79 0.91 f 0.97 0.90 1.04 47.0 55.9 0.84 f 0.78 0.91 f 0.98 0.90 1.06 Crawford et al, Fertil Steril 2017

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 (0.80 0.83) Reference Fresh non-blastocyst 1.22 (1.20 1.24) 1.21 (1.19 1.24) 1.04 (0.98 1.11) 1.15 (1.12 1.18) 0.82 (0.80 0.83) Frozen blastocyst 0.73 (0.72 0.75) Frozen blastocyst 1.36 (1.34 1.39) 1.41 (1.38 1.45) 0.48 (0.43 0.53) 1.29 (1.25 1.32) 0.73 (0.72 0.75) Frozen non-blastocyst 1.57 (1.54 1.61) 1.63 (1.59 1.68) 0.67 (0.60 0.73) Frozen 1.34 non-blastocyst (1.30 1.38) 0.64 0.64 (0.62 0.65) (0.62 0.65) 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=509 938 Wang et al, Fertil Steril 2017

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