Technologies Register Plus (CARTR Plus) Canadian Fertility and - PowerPoint PPT Presentation

Reasons for treatment All ART treatment cycles (fresh and frozen), 2017 Male factor 30.5 Unexplained infertility 19.2 Advanced female age 18.2 Diminished ovarian reserve 15.3 PGT-A 10.3 PCOS 9.1 Tubal factor 9.0 Endometriosis 7.0 Other ovulatory disorder 4.7 4.6 Other female factor 4.1 No male partner Other uterine factor 2.95 Other reasons† 2.4 PGT-M 1.5 Oocyte/embryo banking for cancer treatment 1.2 Oocyte/embryo banking for non-cancer/non-medical reasons 1.2 0 5 10 15 20 25 30 35 Percent per cycle start (%) * Categories are not mutually exclusive † Other reasons include: gonadotoxic therapy, no female partner and peritoneal factor or severe adhesions 25

Clinical pregnancy by type of treatment cycle 2017 60 52 50 46 42 41 41 38 40 37 36 Percent (%) 33 30 26 21 20 17 15 8 10 0 Fresh IVF – own Fresh IVF – donor Natural/modified FET – own oocytes* FET – donor Frozen oocyte IVF – Frozen oocyte IVF – oocytes* oocytes natural IVF* oocytes own oocytes* donor oocytes Per cycle start / embryo thaw cycle Per ET cycle Clinical 136 11 5,009 28 225 2,320 782 pregnancies 26 * Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Singleton ongoing clinical pregnancy by type of treatment cycle 2017 60 50 42 39 40 36 35 35 Percent (%) 32 32 28 30 27 26 20 16 13 12 10 8 0 Fresh IVF – own Fresh IVF – donor Natural/modified FET – own FET – donor Frozen oocyte IVF Frozen oocyte IVF oocytes* oocytes natural IVF* oocytes* oocytes – own oocytes* – donor oocytes Per cycle start / embryo thaw cycle Per ET cycle * Own oocytes exclusively 27 † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

Patient age All ART treatment cycles (fresh and frozen), 2017 60 50 Percent per cycle start (%) 39.1 40 30 23.5 20.1 20 9.9 10 7.3 0 <35 35 – 37 38 – 40 41 – 42 ≥43 Patient age (years) 28

TREATMENT CYCLES FOR 2017 ART cycles using IVF – own oocytes 29

Stage of treatment and treatment outcomes ART cycles using IVF – own oocytes, 2017 16,000 15,391 14,542 14,000 12,000 10,000 8,000 7,000 90.1% of ongoing 6,000 clinical pregnancies 4,000 2,320 2,112 1,902 2,000 0 Cycle starts (CS) Oocyte retrieval Embryo transfer Clinical Ongoing clinical Singleton cycles (RET) cycles (ET) pregnancies* pregnancies† pregnancies‡ 849 cancelled: 7542 no ET: 15.1% per CS 13.7% per CS 12.4% per CS 5.5% per CS 48.1% per RET 16.0% per RET 14.5% per RET 13.1% per RET 33.1% per ET 30.2% per ET 27.2% per ET * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy 30 † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound ‡ Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

Stage of treatment and treatment outcomes ART cycles using IVF – own oocytes, 2017 16,000 15,391 14,542 14,000 12,000 10,000 8,000 7,000 6,000 4,000 2,320 2,112 1,902 2,000 0 Cycle starts (CS) Oocyte retrieval Embryo transfer Clinical Ongoing clinical Singleton cycles (RET) cycles (ET) pregnancies* pregnancies† pregnancies‡ * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy 31 † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound ‡ Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

Percentage of cancelled cycles ART cycles using IVF – own oocytes, 2017 20 15 Percent per cycle start (%) 9.4 10 8.5 6.3 5.5 5.1 5 3.9 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) 32

Reasons for cycle cancellation ART cycles using IVF – own oocytes, 2017 Low ovarian response 78.1 13.6 Other reasons† Premature ovulation 4.7 Patient error 3.2 Premature luteinization 2.1 Patient personal reason 1.1 0 10 20 30 40 50 60 70 80 90 Percent per cancelled cycle (%) 33 * Categories are not mutually exclusive † Other reasons include: patient illness, donor illness, donor personal reason, donor error, no access to ovaries, other (uns pecified)

Percentage of cycles with no embryo transfer ART cycles using IVF – own oocytes, 2017 70 61.8 60 Percent per oocyte retrieval cycle (%) 52.9 51.9 51.9 51.3 50.7 50 40 30 20 10 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) 34

Reasons for no embryo transfer ART cycles using IVF – own oocytes, 2016 Freeze all, other reason than OHSS risk or PGT 25.6 Freeze all, PGT-A 22.4 Freeze all, OHSS risk 17.0 No utilizable embryos 11.2 Freeze all, PGT-M 9.2 No normal fertilization 5.6 Freeze all, other reason than OHSS risk (unknown PGT) 3.7 No oocytes 2.0 No utilizable oocytes 1.6 Inadequate uterine lining 1.0 No sperm 0.8 0 5 10 15 20 25 30 Percent per oocyte retrieval cycle with no embryo transfer (%) 35 * Categories are mutually exclusive

Reasons for no embryo transfer ART cycles using IVF – own oocytes, 2017 Freeze all, other reason than OHSS risk or PGT 26.0 Freeze all, PGT-A 24.8 Freeze all, OHSS risk 18.3 No utilizable embryos 11.7 Freeze all, PGT-M 5.2 No normal fertilization 4.9 Freeze all, other reason than OHSS risk (unknown PGT) 4.8 No oocytes 1.7 No utilizable oocytes 1.5 Inadequate uterine lining 0.9 No sperm 0.4 0 5 10 15 20 25 30 Percent per oocyte retrieval cycle with no embryo transfer (%) 36 * Categories are mutually exclusive

Method of insemination ART cycles using IVF – own oocytes, 2017 90 77.8 80 Percent per oocyte retrieval cycle (%) 70 60 50 40 30 20 13.6 10 5.3 2.2 1.2 0 Conventional IVF only ICSI only Conventional IVF and Rescue ICSI Not done ICSI 37 Conventional IVF and ICSI: a single ET cycle used both conventional IVF and ICSI

Number of embryos transferred ART cycles using IVF – own oocytes, 2017 62.1 60 50 Percent per ET cycle (%) 40 34.3 30 20 eSET 10 eDET 3.7 0 1 embryo 2 embryos ≥3 embryos eSET: eDET: 61.4% per ET=1 47.2% per ET=2 38 * Excludes records with missing number of embryos transferred † Elective single ( eSET) and double (eDET) embryo transfer: transfer of one embryo (eSET) or two embryos (eDET), selected from a larger cohort of available embryos

Number of embryos transferred ART cycles using IVF – own oocytes, 2017 80.3 80 70 57.7 60 Percent per ET cycle (%) 52.3 50 39.9 40 34.9 30 eSET 19.4 20 12.8 eSET eDET 10 eDET 2.3 eDET eSET 0.3 0 1 embryo 2 embryos ≥3 1 embryo 2 embryos ≥3 1 embryo 2 embryos ≥3 embryos embryos embryos <35 years 35 – 39 years ≥40 years 39 Patient age (years)

Embryo transfer day ART cycles using IVF – own oocytes, 2017 70 62.9 60 50 Percent per ET cycle (%) 40 31.6 30 20 10 4.2 1.0 0.4 0 Day 2 Day 3 Day 4 Day 5 Day 6 or 7 40 * Excludes records with missing embryo transfer day

Clinical pregnancy and implantation rate ART cycles using IVF – own oocytes, 2017 60 50 39.0 40 36.9 34.8 33.1 Percent (%) 30.5 28.1 30 25.9 20.0 19.5 20 13.0 10.7 10 6.2 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) Clinical pregnancy, per ET cycle Implantation rate 41 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Clinical pregnancy and implantation rate ART cycles using IVF – own oocytes, 2017 60 50 40 34.2 33.2 33.1 Percent (%) 33.8 30 25.9 21.4 21.2 20 8.7 10 0 1 2 ≥3 OVERALL Number of embryos transferred Clinical pregnancy, per ET cycle Implantation rate 42 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Clinical pregnancy and implantation rate by eSET/eDET ART cycles using IVF – own oocytes, 2017 60 50 41.3 40.9 40 35.7 33.1 Percent (%) 30.9 30 25.9 23.3 22.8 22.7 19.4 20 10 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Clinical pregnancy, per ET cycle Implantation rate NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 43 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Clinical pregnancy and implantation rate ART cycles using IVF – own oocytes, 2017 60 50 37.8 40 33.1 Percent (%) 31.7 30 25.9 26.3 18.3 20 10 0 Day 3 Day 5 OVERALL Embryo transfer day Clinical pregnancy, per ET cycle Implantation rate 44 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Proportion of cycles resulting in an ongoing clinical pregnancy ART cycles using IVF – own oocytes, 2017 60 50 Percent per ET cycle (%) 40 36.5 33.3 30.2 30 25.2 20 16.6 10 6.5 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) Singleton pregnancy Multiple pregnancy * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 45 † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Percentage of multiple pregnancies ART cycles using IVF – own oocytes, 2017 40 Percent per ongoing clinical pregnancy (%) 28.6 30 20 16.0 13.1 11.0 9.9 10 7.2 S 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) Multiple 74 62 50 20 4 210 pregnancies * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 46 † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Proportion of cycles resulting in an ongoing clinical pregnancy ART cycles using IVF – own oocytes, 2017 60 50 Percent per ET cycle (%) 40 31.8 30.2 23.9 30 15.2 20 10 0 1 2 ≥3 OVERALL Number of embryos transferred Singleton pregnancy Multiple pregnancy NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 47 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Percentage of multiple pregnancies ART cycles using IVF – own oocytes, 2017 40 Percent per ongoing clinical pregnancy (%) 30 25.2 20.4 20 9.9 10 1.7 0 1 2 ≥3 OVERALL Number of embryos transferred Multiple 23 177 10 210 pregnancies NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 48 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Proportion of cycles resulting in an ongoing clinical pregnancy by plurality and eSET/eDET ART cycles using IVF – own oocytes, 2017 60 50 Percent per ET cycle (%) 37.9 40 31.7 30.2 30 27.2 20.9 20 10 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Singleton pregnancy Multiple pregnancy NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 49 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Percentage of multiple pregnancies by eSET/eDET ART cycles using IVF – own oocytes, 2017 40 Percent per ongoing clinical pregnancy (%) 30 27.1 23.2 20 9.9 10 2.0 0.9 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Multiple 20 3 97 80 210 pregnancies NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 50 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Proportion of cycles resulting in an ongoing clinical pregnancy ART cycles using IVF – own oocytes, 2017 60 50 Percent per ET cycle (%) 40 34.5 30.2 30 23.9 20 10 0 Day 3 Day 5 OVERALL Embryo transfer day Singleton pregnancy Multiple pregnancy * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 51 † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Percentage of multiple pregnancies ART cycles using IVF – own oocytes, 2017 40 Percent per ongoing clinical pregnancy (%) 30 20 11.2 9.9 9.6 10 0 Day 3 Day 5 OVERALL Embryo transfer day Multiple 59 145 210 pregnancies 52 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Treatment outcomes ART cycles using IVF – own oocytes, 2017 Treatment outcome Number % per CS % per ET % per CP % per OCP Clinical pregnancy (CP) * 2,320 15.1 33.1 Ongoing clinical pregnancy (OCP) † 2,112 13.7 30.2 91.0 Singleton‡ 1,902 12.4 27.2 82.0 90.1 Multiple‡ 210 1.36 3.00 9.1 9.9 Multiple pregnancy‡ 210 1.36 3.00 9.1 9.9 Twins 207 98.6% of multiple pregnancies were twin gestations Triplet or higher 3 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 53 ‡ Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Oocyte retrieval, embryo transfer, clinical pregnancy and singleton pregnancy ART cycles using IVF – own oocytes, 2017 120 96 100 95 94 94 92 91 80 Percent per CS (%) 60 47 47 45 45 43 40 35 18 17 16 20 15 14 13 12 10 8 6 4 2 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) Retrieval Embryo transfer Clinical pregnancy* Singleton pregnancy† 54 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

TREATMENT CYCLES FOR 2017 ART cycles using FET – own oocytes 55

Stage of treatment and treatment outcomes ART cycles using FET – own oocytes, 2017 14,000 13,261 13,417 12,000 10,000 8,000 6,000 5,009 4,527 4,223 4,000 2,000 0 Embryo thaw cycles Embryo transfer cycles Clinical pregnancies* Ongoing clinical Singleton pregnancies‡ (ET) pregnancies† 156 no ET: 37.3% per thaw 33.7% per thaw 31.5% per thaw 1.2% per thaw 37.8% per ET 34.1% per ET 31.8% per ET * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy 56 † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound ‡ Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

Method of embryo cryopreservation ART cycles using FET – own oocytes, 2017 96.8 100 80 Percent per embryo thaw cycle (%) 60 40 20 3.1 0.1 0 Vitrification Slow freezing Mixed 57

Percentage of no embryo transfer ART cycles using FET – own oocytes, 2017 10 8 Percent per embryo thaw cycle (%) 6 4.6 4 2.1 2 1.2 1.1 1.1 1.0 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) 58

Number of embryos transferred ART cycles using FET – own oocytes, 2017 90 82.7 80 70 Percent per ET cycle (%) 60 50 40 30 16.9 20 eSET 10 0.4 eDET 0 1 embryo 2 embryos ≥3 embryos eSET: eDET: 52.4% per ET=1 46.5% per ET=2 59 * Elective single (eSET) and double (eDET) embryo transfer: transfer of one embryo (eSET) or two embryos (eDET), selected from a larger cohort of available embryos

Number of embryos transferred ART cycles using FET – own oocytes, 2017 87.0 90 80.9 80 66.7 70 Percent per ET cycle (%) 60 50 40 31.6 30 18.8 eSET 20 eSET 12.8 eSET 10 eDET 1.6 0.3 0.1 eDET eDET 0 1 embryo 2 embryos ≥3 1 embryo 2 embryos ≥3 1 embryo 2 embryos ≥3 embryos embryos embryos <35 years 35 – 39 years ≥40 years Age at time of oocyte retrieval (years) 60

Clinical pregnancy and implantation rate ART cycles using FET – own oocytes, 2017 50 40.9 38.7 38.3 37.8 40 35.0 34.4 31.2 Percent (%) 30 26.7 26.1 20.4 19.9 20 14.8 10 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) Clinical pregnancy, per ET cycle Implantation rate 61 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Clinical pregnancy and implantation rate ART cycles using FET – own oocytes, 2017 50 41.7 37.8 40 37.6 37.1 34.4 30 Percent (%) 27.3 20 16.3 7.8 10 0 1 2 ≥3 OVERALL Number of embryos transferred Clinical pregnancy, per ET cycle Implantation rate 62 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Clinical pregnancy and implantation rate by eSET/eDET ART cycles using FET – own oocytes, 2017 50 44.0 42.4 41.7 39.6 37.8 40 34.4 32.4 32.0 29.0 30 Percent (%) 25.9 20 10 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Clinical pregnancy, per ET cycle Implantation rate NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 63 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Proportion of cycles resulting in an ongoing clinical pregnancy ART cycles using FET – own oocytes, 2017 50 40 37.1 34.8 34.1 Percent per ET cycle (%) 27.7 30 22.7 20 17.2 10 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) Singleton pregnancy Multiple pregnancy 64 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Percentage of multiple pregnancies ART cycles using FET – own oocytes, 2017 40 Percent per ongoing clinical pregnancy (%) 30 20 8.3 10 6.8 6.7 6.3 6.0 5.4 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) Multiple 181 66 47 8 2 304 pregnancies * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 65 † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Proportion of cycles resulting in an ongoing clinical pregnancy ART cycles using FET – own oocytes, 2017 50 40 37.0 34.1 33.6 Percent per ET cycle (%) 30 20 16.3 10 0 1 2 ≥3 OVERALL Number of embryos transferred Singleton pregnancy Multiple pregnancy NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 66 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Percentage of multiple pregnancies ART cycles using FET – own oocytes, 2017 60 50.0 Percent per ongoing clinical pregnancy (%) 50 40 28.5 30 20 10 6.7 1.7 0 1 2 ≥3 OVERALL Number of embryos transferred Multiple 64 236 4 304 pregnancies NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 67 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Proportion of cycles resulting in an ongoing clinical pregnancy by plurality and eSET/eDET ART cycles using FET – own oocytes, 2017 60 50 39.6 Percent per ET cycle (%) 38.0 40 34.7 34.1 28.8 30 20 10 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Singleton pregnancy Multiple pregnancy NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 68 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Percentage of multiple pregnancies by eSET/eDET ART cycles using FET – own oocytes, 2017 40 Percent per ongoing clinical pregnancy (%) 28.6 28.4 30 20 10 6.7 2.0 1.6 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Multiple 34 30 118 118 304 pregnancies NOTE: In rare cases, a single embryo may divide and produce twins or triplets. For this reason, a small percentage of multiple pregnancies can result from a single embryo transfer 69 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Treatment outcomes ART cycles using FET – own oocytes, 2017 Treatment outcome Number % per % per ET % per CP % per OCP embryo thaw Clinical pregnancy (CP) * 5,009 37.3 37.8 Ongoing clinical pregnancy (OCP) † 4,527 33.7 34.1 90.4 Singleton‡ 4,223 31.5 31.8 84.3 93.3 Multiple‡ 304 2.3 2.3 6.1 6.7 Multiple pregnancy‡ 304 97.7% of multiple pregnancies were twin gestations 2.5 2.5 7.1 7.9 Twins 297 Triplet or higher 7 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy 70 † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound ‡ Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound; multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat

Embryo transfer, clinical pregnancy and singleton clinical pregnancy ART cycles using FET – own oocytes, 2017 99 99 99 98 99 100 95 80 Percent per embryo thaw cycle (%) 60 40 38 37 40 34 32 31 31 26 25 21 19 20 15 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) Embryo transfer Clinical pregnancy* Singleton pregnancy† 71 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

OVERALL SUMMARY 72

Clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle 2017 60 50 Percent per CS/embryo thaw cycle (%) 42 42 42 41 40 40 37 36 31 30 26 24 18 20 17 16 15 15 14 9 10 8 5 0 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL 73 * Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle 2017 70 60 56 52 51 52 50 Percent per ET cycle (%) 43 42 41 41 39 38 38 40 36 34 33 31 30 27 26 25 21 20 10 0 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL 74 * Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Implantation rate 2017 60 49 50 39 40 38 34 Percent (%) 28 30 26 26 20 10 0 Fresh IVF – own Fresh IVF – donor Natural/modified FET – own FET – donor Frozen oocyte IVF Frozen oocyte IVF oocytes* oocytes natural IVF* oocytes* oocytes – own oocytes* – donor oocytes Type of treatment cycle 75 * Own oocytes exclusively † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Implantation rate by age at time of oocyte retrieval and type of treatment cycle 2017 60 51 49 50 43 42 39 39 38 40 38 36 35 34 Percent (%) 32 29 30 27 26 26 25 21 20 14 10 0 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL 76 * Own oocytes exclusively † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Singleton ongoing clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle 2017 60 50 Percent per CS/embryo thaw cycle (%) 40 37 35 35 34 33 32 30 30 25 21 20 20 16 14 13 13 12 12 10 8 6 5 0 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL * Own oocytes exclusively 77 † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

Singleton ongoing clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle 2017 60 50 44 42 42 41 Percent per ET cycle (%) 40 38 37 36 35 35 34 32 31 30 27 27 26 25 25 22 20 15 10 0 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL * Own oocytes exclusively † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound 78

PRIMARY TRANSFER PREGNANCY RATE 79

Primary transfer • Cohort: – Patients with first IVF cycle in CARTR Plus and no documented prior treatment cycle using own oocytes – The first treatment cycle with an embryo transfer • IVF with own oocytes • FET with own oocytes 80

Primary transfer rate • Several options for calculation: – Per patient: treatment cycle outcomes can be linked for a patient throughout the database – Per batch of oocytes collected: treatment cycles that used frozen oocytes or embryos can be linked to the IVF cycle where the oocytes were collected 81

Primary transfer clinical pregnancy rate per patient IVF and FET, 2013, 2014, 2015, 2016 and 2017 100 80 Percent per primary transfer (%) 60 45.5 40.4 40 35.0 20 0 <35 ≥35 OVERALL Patient age (years) Clinical 13,623 9,947 23,570 pregnancy 82 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Primary transfer clinical pregnancy rate per patient by oocyte type per patient IVF and FET, 2013, 2014, 2015, 2016 and 2017 100 80 Percent per primary transfer (%) 60 46.5 40.4 39.9 40 20 0 Own Donor OVERALL Clinical 21,707 1,863 23,570 pregnancy 83 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Primary transfer clinical pregnancy rate per patient with and without PGT-A IVF and FET, 2013, 2014, 2015, 2016 and 2017 100 80 Percent per primary transfer (%) 60 50.6 40.4 39.9 40 20 0 Excluding cycles with PGT-A Cycles with PGT-A OVERALL Clinical 22,316 1,254 23,570 pregnancy 84 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Primary transfer clinical pregnancy rate per batch of oocytes IVF and FET, 2013, 2014, 2015, 2016 and 2017 100 80 Percent per primary transfer (%) 60 46.8 39.7 40 34.4 20 0 <35 ≥35 OVERALL Patient age (years) Clinical 12,021 11,899 23,920 pregnancy 85 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Primary transfer clinical pregnancy rate per batch of oocytes with and without PGT-A IVF and FET, 2013, 2014, 2015, 2016 and 2017 100 80 Percent per primary transfer (%) 60 49.3 39.7 39.2 40 20 0 Excluding cycles with PGT-A Cycles with PGT-A OVERALL Clinical 22,506 1,414 23,920 pregnancy 86 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

CUMULATIVE PREGNANCY RATE 87

Cumulative pregnancy rate • Definition: – The number of clinical pregnancies resulting from one or more ART cycles, including the cycle when fresh embryos are transferred and all related subsequent frozen/thawed embryo transfer cycles if the fresh embryo transfer did not result in a pregnancy • Rationale: – Estimates cumulative success with ongoing treatment, rather than success per individual stage of the treatment process 88

Cumulative pregnancy rate • Several options for calculation: – Per patient: treatment cycle outcomes can be linked for a patient throughout the database – Per batch of oocytes collected: treatment cycles that used frozen oocytes or embryos can be linked to the IVF cycle where the oocytes were collected 89

Cumulative pregnancy rate • Optimistic: – Assumes that women who did not return for subsequent treatment cycles had the same chance of a clinical pregnancy as those who did return for treatment • Conservative: – Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy Malizia BA et al., NEJM 2009; 360: 236-243 90

Cumulative pregnancy rate, per patient All ART treatment cycles (fresh and frozen), 2013, 2014, 2015, 2016 and 2017 100 90 80 Probability of clinical pregnancy (%) 73.0 70 63.6 60 49.2 50 50.2 47.7 40 41.4 25.2 30 20 25.2 10 0 1 2 3 4 Cycle number Optimistic Conservative 91 Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy Optimistic: Assumes that women who did not return for subsequent treatment cycles had the same chance of a clinical pregnancy as those who did return for treatment. Conservative: Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy.

Cumulative pregnancy rate, per batch of oocytes retrieved IVF and FET – using own oocytes, 2013, 2014, 2015, 2016 and 2017 100 90 79.5 80 Probability of clinical pregnancy (%) 70.6 70 55.1 60 50 40 39.6 39.1 36.4 30 24.0 20 24.0 10 0 1 2 3 4 Cycle number Optimistic Conservative 92 Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy Optimistic: Assumes that women who did not return for subsequent treatment cycles had the same chance of a clinical pregnancy as those who did return for treatment. Conservative: Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy.

Optimistic cumulative pregnancy rate, per batch of oocytes retrieved IVF and FET – using own oocytes, 2013 ,2014, 2015, 2016 and 2017 100 90 83.6 75.9 80 Probability of clinical pregnancy (%) 70 74.7 61.1 60 65.0 50 49.7 40 29.4 30 20 20.4 10 0 1 2 3 4 Cycle number <35 years ≥35 years Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy 93 Optimistic: Assumes that women who did not return for subsequent treatment cycles had the same chance of a clinical pregnancy as those who did return for treatment.

Conservative cumulative pregnancy rate, per batch of oocytes retrieved IVF and FET – using own oocytes, 2013, 2014, 2015, 2016 and 2017 100 90 80 Probability of clinical pregnancy (%) 70 60 50.8 49.9 45.9 50 40 29.4 30 32.0 31.6 29.8 20 20.4 10 0 1 2 3 4 Cycle number <35 years ≥35 years 94 Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy Conservative: Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy. .

Cumulative pregnancy rate, per batch of oocytes retrieved IVF and FET – using own oocytes, 2013, 2014, 2015, 2016 and 2017 Optimistic cumulative pregnancy rate 100 83.6 Probability of clinical pregnancy (%) 75.9 80 61.1 74.7 60 65.0 29.4 40 49.7 20 20.4 0 Conservative cumulative pregnancy rate 100 Probability of clinical pregnancy (%) 80 50.8 49.9 60 45.9 29.4 40 20 32.0 31.6 29.8 20.4 0 1 2 3 4 Cycle number <35 years ≥35 years 95 Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy Optimistic: Assumes that women who did not return for subsequent treatment cycles had the same chance of a clinical pregnancy as those who did return for treatment. Conservative: Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy.

Cumulative pregnancy rate, per batch of oocytes retrieved PGT-A/PGT-M – IVF and FET – using own oocytes 2013, 2014, 2015, 2016 and 2017 100 90 82.3 80 Probability of clinical pregnancy (%) 72.0 70 60 52.8 50 40 30 31.7 31.0 27.4 20 10 2.7 2.7 0 1 2 3 4 Cycle number Optimistic Conservative 96 Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy Optimistic: Assumes that women who did not return for subsequent treatment cycles had the same chance of a clinical pregnancy as those who did return for treatment. Conservative: Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy.

Cumulative pregnancy rate, per batch of oocytes retrieved PGT-A/PGT-M – IVF and FET – own oocytes with an embryo transfer 2013, 2014, 2015, 2016 and 2017 100 90 83.6 80 73.5 Probability of clinical pregnancy (%) 70 60 54.6 59.5 58.2 50 51.3 40 30 20 5.0 10 5.0 0 1 2 3 4 Cycle number Optimistic Conservative 97 Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy Optimistic: Assumes that women who did not return for subsequent treatment cycles had the same chance of a clinical pregnancy as those who did return for treatment. Conservative: Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy.

BIRTH OUTCOMES FOR 2016 All ART treatment cycles (fresh and frozen) 98

Birth outcomes All ART treatment cycles (fresh and frozen), 2016 7,000 6,514 5,957 6,000 5,070 5,000 4,000 3,000 2,000 1,000 0 Live birth Singleton live birth Live birth Good perinatal outcome* 99 * Good perinatal outcome: singleton live birth at ≥37 weeks’ gestation and a birth weight ≥2,500 grams † Cycle starts, oocyte retrievals/thaws and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

Birth outcome rates All ART treatment cycles (fresh and frozen), 2016 100 77.5 80 70.9 60.3 60 Percent (%) 40 29.4 26.8 22.8 22.1 21.5 20.2 19.6 17.2 20 16.7 0 Per CS Per RET/THAW Per ET Per OCP Live birth Singleton live birth Live birth Good perinatal outcome* * Good perinatal outcome: singleton live birth at ≥37 weeks’ gestation and a birth weight ≥2,500 grams 100 OCP - Ongoing clinical pregnancy: a clinical pregnancy with documentation of at least one fetal heart beat on ultrasound Cycle starts, oocyte retrievals/thaws and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)