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

Proportion of miscarriage and stillbirth rates ART cycles using FET – own oocytes, 2015 50 40 Percent per ET cycle (%) 31.3 28.2 30 27.3 20 15.0 8.5 8.3 8.2 8.3 10 0.34 0.27 0.30 0.31 0 Live birth MiscarriageƗ Stillbirth* <35 35 – 39 ≥40 OVERALL Age at time of oocyte retrieval (years) 24 * Stillbirths: birth outcome where no fetus(es) was born alive and at least one stillbirth at ≥ 20 weeks’ gestation Ɨ Miscarriage: birth outcome where all fetuses were a ‘pregnancy loss’ at <20 weeks’ gestation

Percentage of birth outcomes by method of insemination ART cycles using IVF – own oocytes, 2015 50 47.8 44.0 38.6 40 37.2 36.6 35.7 32.7 Percent per ET cycle (%) 31.2 29.2 30 25.6 25.5 21.9 20 10 0 Conventional IVF only ICSI only Conventional IVF and ICSI Ongoing clinical pregnancy Live birth Singleton live birth Live birth - Good perinatal outcome* 25 * Good perinatal outcome: singleton live birth at ≥37 weeks’ gestation and a birth weight ≥2,500 grams † Conventional IVF and ICSI: a single ET cycle used both conventional IVF and ICSI

Proportion of singleton and multiple live births Baby level - All ART treatment cycles (fresh and frozen), 2015 1.25 3.2 100 6.06 80 35.4 41.4 60 Percent (%) 40 20 96.8 57.4 58.6 0 1 embryo 2 embryos ≥3 embryos Singleton live birth Twin live birth Triplet+ live birth Live births 4,067 2,798 198 26 Singleton live birth: one live birth Twin live birth: two births and at least one live birth Triplet+ live birth: three or more births and at least one live birth

Proportion of preterm births by plurality Baby level - All ART treatment cycles (fresh and frozen), 2015 100 80 Percent per live birth (%) 62 60 59 60 48 40 20 16 10 10 10 0 Singleton Multiple Fresh IVF – own oocytes* Fresh IVF – donor oocytes FET – own oocytes* FET – donor oocytes * Own oocytes exclusively 27 Preterm birth <37 weeks’ gestation Total number of live births were used as the denominator for these calculations .

Birth outcomes by province All ART treatment cycles (fresh and frozen), 2015 50 40 Percent per cycle start (%) 30 27 22 22 19 19 19 18 20 16 16 10 0 Ontario Quebec Rest of Canada Live birth Singleton live birth Live birth Good perinatal outcome* 28 * Good perinatal outcome: singleton live birth at ≥37 weeks’ gestation and a birth weight ≥2,500 grams Cycle starts, and embryo transfers with an unknown birth outcome were removed from the denominator (n=353)

Birth outcomes by province All ART treatment cycles (fresh and frozen), 2015 50 40 34 Percent per ET cycle (%) 30 29 30 27 26 26 24 22 22 20 10 0 Ontario Quebec Rest of Canada Live birth Singleton live birth Live birth Good perinatal outcome* 29 * Good perinatal outcome: singleton live birth at ≥37 weeks’ gestation and a birth weight ≥2,500 grams Cycle starts, and embryo transfers with an unknown birth outcome were removed from the denominator (n=353)

Percentage of multiple live births by province Baby level - All ART treatment cycles (fresh and frozen), 2015 40 30 28.0 Percent per live birth (%) 22.5 19.9 20 10 5.2 0 Ontario Quebec Rest of Canada OVERALL Multiple 600 97 708 1,405 births 30 Ongoing clinical pregnancy: documentation of at least one fetal heart beat on ultrasound Multiple birth: At least one live birth from a multiple pregnancy

TREATMENT CYCLES FOR 2016 All ART treatment cycles (fresh and frozen) 31

Number of treatment cycles 2016 16,000 15,344 14,000 12,071 11,902 12,000 10,000 8,084 8,000 6,000 4,000 1,587 1,580 2,000 754 460 343 426 178 125 57 58 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 Cycle starts / Embryo thaw cycles ET cycles 32 * Own oocytes exclusively

Number of treatment cycles 2015 16,000 15,273 14,000 12,000 10,000 9,526 9,251 9,075 8,000 6,000 4,000 2,000 1,229 1,233 956 722 479 417 383 331 83 51 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 Cycle starts / Embryo thaw cycles ET cycles 33 * Own oocytes exclusively

Type of treatment cycle, per cycle start All ART treatment cycles (fresh and frozen), 2016 IVF 51.6 FET 43.8 Frozen oocyte IVF 1.9 Oocyte banking 2.0 IVM 0.1 0 20 40 60 80 Percent (%) 34

Type of treatment cycle, per cycle start All ART treatment cycles (fresh and frozen), 2016 Fresh IVF – own oocytes* 49.2 Fresh IVF – donor oocytes 2.4 Natural/modified natural IVF* 0.6 FET – own oocytes* 38.7 FET – donor oocytes 5.1 Frozen oocyte IVF – own oocytes* 0.4 Frozen oocyte IVF – donor oocytes 1.5 Oocyte banking 2.0 IVM 0.1 0 20 40 60 80 Percent (%) 35 * Own oocytes exclusively

Type of treatment cycle, per cycle start All ART treatment cycles (fresh and frozen), 2016 Type of treatment cycle Number Percent IVF – own oocytes* 15,344 49.22 IVF – donor oocytes 754 2.42 Natural/modified natural IVF* 178 0.57 FET – own oocytes* 12071 38.72 FET – donor oocytes 1587 5.09 Frozen oocyte IVF – own oocytes* 125 0.40 Frozen oocyte IVF – donor oocytes 460 1.48 Oocyte banking 626 2.01 IVM 27 0.09 TOTAL TREATMENT CYCLES 31,174 36 * Own oocytes exclusively

Reasons for treatment All ART treatment cycles (fresh and frozen), 2016 Male factor 30.4 Unexplained infertility 19.7 Advanced female age 18.0 14.3 Diminished ovarian reserve Tubal factor 9.0 PGS/PGD 8.9 PCOS 8.4 Endometriosis 7.0 Other ovulatory disorder 4.8 4.5 Other female factor No male partner 3.4 Other uterine factor 2.9 Other reasons† 1.7 Oocyte/embryo banking for cancer treatment 1.2 Oocyte/embryo banking for non-cancer/non-medical reasons 1.0 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 37

Clinical pregnancy by type of treatment cycle 2016 60 50 50 47 43 40 36 35 36 35 Percent (%) 33 32 31 30 23 20 17 14 10 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 172 18 4,276 18 199 2,681 561 pregnancies 38 * Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Singleton ongoing clinical pregnancy by type of treatment cycle 2016 60 50 41 40 34 Percent (%) 31 30 30 30 29 30 28 27 25 19 20 14 11 9 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 Per cycle start / embryo thaw cycle Per ET cycle * Own oocytes exclusively 39 † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

Specialized services All ART treatment cycles (fresh and frozen), 2016 Description Number of cycles Gestational carrier 639 Pre-implantation genetic screening and/or diagnosis (PGS/PGD) 4,475 Oocyte or embryo banking due to cancer treatment 378 Oocyte or embryo banking due to non-cancer/non-medical reasons 325 Any use of donor oocytes or embryos 2,826 Frozen oocyte IVF 585 40

Oocyte or embryo freezing for non-medical reasons 2013, 2014, 2015, 2016 Year Number of cycles 2013 132 2014 174 2015 280 2016 325 Overall 911 41

Patient age All ART treatment cycles (fresh and frozen), 2016 60 50 Percent per cycle start (%) 38.8 40 30 23.5 20.3 20 10.2 10 7.2 0 <35 35 – 37 38 – 40 41 – 42 ≥43 Patient age (years) 42

TREATMENT CYCLES FOR 2016 ART cycles using IVF – own oocytes 43

Stage of treatment and treatment outcomes ART cycles using IVF – own oocytes, 2016 16,000 15,344 14,606 14,000 12,000 10,000 8,084 8,000 88.3% of ongoing 6,000 clinical pregnancies 4,000 2,681 2,438 2,152 2,000 0 Cycle starts (CS) Oocyte retrieval Embryo transfer Clinical Ongoing clinical Singleton cycles (RET) cycles (ET) pregnancies* pregnancies† pregnancies‡ 738 cancelled: 6522 no ET: 17.5% per CS 21.6% per CS 15.9% per CS 4.8% per CS 44.7% per RET 18.4% per RET 23.1% per RET 16.7% per RET 33.2% per ET 36.4% per ET 30.2% per ET * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy 44 † 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, 2016 16,000 15,344 14,606 14,000 12,000 10,000 8,084 8,000 6,000 4,000 2,681 2,438 2,152 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 45 † 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, 2016 20 15 Percent per cycle start (%) 10 7.8 6.4 5.8 4.8 4.7 5 3.6 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) 46

Reasons for cycle cancellation ART cycles using IVF – own oocytes, 2016 Low ovarian response 77.5 Other reasons† 16.1 Premature ovulation 3.1 Patient personal reason 1.8 High ovarian response 0.7 Patient error 2.3 Premature luteinization 1.4 0 10 20 30 40 50 60 70 80 90 Percent per cancelled cycle (%) 47 * 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, 2016 60 56.3 49.2 50 46.5 Percent per oocyte retrieval cycle (%) 44.7 42.7 42.3 40 30 20 10 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) 48

Reasons for no embryo transfer ART cycles using IVF – own oocytes, 2016 Freeze all, other reason than OHSS risk or PGS/PGD 25.6 Freeze all, PGS 22.4 Freeze all, OHSS risk 17.0 No utilizable embryos 11.2 Freeze all, PGD 9.2 No normal fertilization 5.6 Freeze all, other reason than OHSS risk (unknown PGS/PGD) 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 (%) 49 * Categories are mutually exclusive

Reasons for no embryo transfer ART cycles using IVF – own oocytes, 2015 Freeze all, other reason than OHSS risk (unknown PGS/PGD) 32.4 Freeze all, OHSS risk 18.0 No utilizable embryos 15.7 No normal fertilization 9.4 Freeze all, PGD 6.8 Freeze all, other reason than OHSS risk or PGS/PGD 6.0 Freeze all, PGS 5.9 No oocytes 2.9 No utilizable oocytes 1.6 No sperm 0.7 Inadequate uterine lining 0.7 0 5 10 15 20 25 30 35 Percent per oocyte retrieval cycle with no embryo transfer (%) 50 * Categories are mutually exclusive

Method of insemination ART cycles using IVF – own oocytes, 2016 76.8 80 70 Percent per oocyte retrieval cycle (%) 60 50 40 30 20 13.2 10 4.5 3.1 2.5 0 Conventional IVF only ICSI only Conventional IVF and Rescue ICSI Not done ICSI 51 Conventional IVF and ICSI: a single ET cycle used both conventional IVF and ICSI

Number of embryos transferred ART cycles using IVF – own oocytes, 2016 59.2 60 50 Percent per ET cycle (%) 40 36.7 30 20 eSET 10 4.1 eDET 0 1 embryo 2 embryos ≥3 embryos eSET: eDET: 59.5% per ET=1 43.7% per ET=2 52 * 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, 2016 77.1 80 70 60 Percent per ET cycle (%) 54.8 54.5 50 42.5 40 32.2 30 eSET 22.3 20 13.0 eSET eDET 10 eDET 3.0 eDET 0.7 eSET 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 53 Patient age (years)

Embryo transfer day ART cycles using IVF – own oocytes, 2016 65 58.66 55 45 Percent per ET cycle (%) 35.21 35 25 15 4.5 5 1.15 0.46 Day 2 Day 3 Day 4 Day 5 Day 6 or 7 -5 54 * Excludes records with missing embryo transfer day

Clinical pregnancy and implantation rate ART cycles using IVF – own oocytes, 2016 60 50 40.4 40 35.3 34.7 33.2 Percent (%) 29.5 29.1 30 25.7 20.5 20 17.1 11.2 9.9 10 4.9 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) Clinical pregnancy, per ET cycle Implantation rate 55 * 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, 2016 60 50 40 34.4 33.2 33.2 Percent (%) 33.7 30 25.7 24.7 21.4 20 10.3 10 0 1 2 ≥3 OVERALL Number of embryos transferred Clinical pregnancy, per ET cycle Implantation rate 56 * 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, 2016 60 50 41.0 40.2 40 34.4 33.2 Percent (%) 32.3 30 25.7 24.7 24.3 22.1 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 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 57 * 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, 2016 60 50 39.2 40 33.2 Percent (%) 30 25.7 25.9 17.4 20 12.8 10 0 Day 3 Day 5 OVERALL Embryo transfer day Clinical pregnancy, per ET cycle Implantation rate 58 * 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, 2016 60 50 Percent per ET cycle (%) 37.6 40 31.9 30.1 30 25.6 20 13.5 10 7.0 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 59 † 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, 2016 40 Percent per ongoing clinical pregnancy (%) 30 20 16.4 14.7 13.7 11.7 8.5 10 5.9 S 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) Multiple 105 91 73 16 S 286 pregnancies * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 60 † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound S Numbers less than 6 were suppressed

Proportion of cycles resulting in an ongoing clinical pregnancy ART cycles using IVF – own oocytes, 2016 60 50 Percent per ET cycle (%) 40 31.1 30.2 29.9 30 19.2 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 61 * 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, 2016 40 Percent per ongoing clinical pregnancy (%) 30 27.0 26.6 20 11.7 10 2.2 0 1 2 ≥3 OVERALL Number of embryos transferred Multiple 33 236 17 286 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 62 * 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, 2016 60 50 Percent per ET cycle (%) 40 37.1 31.0 30.2 29.0 30 22.2 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 63 * 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, 2016 40 Percent per ongoing clinical pregnancy (%) 30 27.1 26.2 20 11.7 10 2.3 2.2 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Multiple 23 10 109 127 286 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 64 * 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, 2016 60 50 Percent per ET cycle (%) 40 35.5 30.2 30 24.0 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 65 † 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, 2016 40 Percent per ongoing clinical pregnancy (%) 30 20 17.5 11.7 9.6 10 0 Day 3 Day 5 OVERALL Embryo transfer day Multiple 119 161 286 pregnancies 66 * 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, 2016 Treatment outcome Number % per CS % per ET % per CP % per OCP Clinical pregnancy (CP) * 2,681 17.5 33.2 Ongoing clinical pregnancy (OCP) † 2,438 15.9 30.2 90.9 Singleton‡ 2,152 14.0 26.7 10.6 88.3 Multiple‡ 286 1.86 3.53 80.3 11.7 Multiple pregnancy‡ 286 1.86 3.54 10.7 11.7 Twins 274 95.8% of multiple pregnancies were twin gestations Triplet or higher 12 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 67 ‡ 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, 2016 120 96 95 100 95 94 94 92 80 Percent per CS (%) 56 60 55 53 50 48 40 40 22 19 19 17 20 15 15 14 11 8 6 4 3 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Patient age (years) Retrieval Embryo transfer Clinical pregnancy* Singleton pregnancy† 68 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

TREATMENT CYCLES FOR 2016 ART cycles using FET – own oocytes 69

Stage of treatment and treatment outcomes ART cycles using FET – own oocytes, 2016 14,000 11,902 12,071 12,000 10,000 8,000 6,000 4,276 3,836 3,534 4,000 2,000 0 Embryo thaw cycles Embryo transfer cycles Clinical pregnancies* Ongoing clinical Singleton pregnancies‡ (ET) pregnancies† 169 no ET: 35.4% per thaw 31.8% per thaw 29.3% per thaw 1.4% per thaw 35.9% per ET 32.2% per ET 29.7% per ET * 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

Percentage of no embryo transfer ART cycles using FET – own oocytes, 2016 10 8 Percent per embryo thaw cycle (%) 6 4 3.2 2 1.5 1.4 1.3 1.2 1.1 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) 71

Number of embryos transferred ART cycles using FET – own oocytes, 2016 79.1 80 70 60 Percent per ET cycle (%) 50 40 30 20.2 20 eSET 10 eDET 0.7 0 1 embryo 2 embryos ≥3 embryos eSET: eDET: 50.1% per ET=1 45.1% per ET=2 72 * 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, 2016 90 84.1 77.1 80 70 62.1 Percent per ET cycle (%) 60 50 40 35.0 30 22.3 eSET 20 15.6 eSET eSET 10 eDET 2.9 0.6 0.3 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) 73

Method of embryo cryopreservation ART cycles using FET – own oocytes, 2016 100 94.3 80 Percent per embryo thaw cycle (%) 60 40 20 5.6 0.1 0 Vitrification Slow freezing Mixed 74

Clinical pregnancy and implantation rate ART cycles using FET – own oocytes, 2016 50 40 38.3 36.3 35.8 35.9 33.6 32.9 32.1 Percent (%) 30 27.5 22.4 21.8 20 16.7 16.1 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 75 * 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, 2016 50 39.0 40 35.8 35.9 35.2 32.1 29.4 30 Percent (%) 26.0 20 12.1 10 0 1 2 ≥3 OVERALL Number of embryos transferred Clinical pregnancy, per ET cycle Implantation rate 76 * 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, 2016 50 38.7 39.3 40 37.5 36.8 35.9 34.1 33.6 32.1 30 Percent (%) 26.1 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 77 * 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, 2016 50 40 34.8 Percent per ET cycle (%) 32.5 32.2 29.3 30 18.5 20 17.6 10 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) Singleton pregnancy Multiple pregnancy 78 * 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, 2016 40 Percent per ongoing clinical pregnancy (%) 30 20 10 8.2 8.0 7.9 7.6 6.8 5.4 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) Multiple 178 70 44 8 S 302 pregnancies * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound 79 † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound S Numbers less than 6 were suppressed

Proportion of cycles resulting in an ongoing clinical pregnancy ART cycles using FET – own oocytes, 2016 50 40 34.4 Percent per ET cycle (%) 32.2 31.7 28.2 30 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 80 * 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, 2016 40 Percent per ongoing clinical pregnancy (%) 29.0 30 25.0 20 10 7.9 1.9 0 1 2 ≥3 OVERALL Number of embryos transferred Multiple 57 239 6 302 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 81 * 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, 2016 60 50 Percent per ET cycle (%) 40 34.6 34.2 33.6 32.2 29.9 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 82 * 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, 2016 40 Percent per ongoing clinical pregnancy (%) 30.1 30 28.0 20 10 7.9 2.1 1.8 0 Elective single embryo Non-elective single Elective double embryo Non-elective double OVERALL transfer (eSET) embryo transfer transfer (eDET) embryo transfer Multiple 28 29 113 126 302 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 83 * 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, 2016 Treatment outcome Number % per % per ET % per CP % per OCP embryo thaw Clinical pregnancy (CP) * 4,276 35.4 35.9 Ongoing clinical pregnancy (OCP) † 3,836 31.8 32.2 89.7 Singleton‡ 3,534 29.3 29.7 82.6 92.1 Multiple‡ 302 2.5 2.5 7.1 7.9 Multiple pregnancy‡ 302 96.7% of multiple pregnancies were twin gestations 2.5 2.5 7.1 7.9 Twins 292 Triplet or higher 10 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy 84 † 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, 2016 98 99 99 99 99 97 100 80 Percent per embryo thaw cycle (%) 60 38 40 36 35 33 32 30 29 27 22 22 17 20 16 0 <35 35 – 37 38 – 40 41 – 42 ≥43 OVERALL Age at time of oocyte retrieval (years) Embryo transfer Clinical pregnancy* Singleton pregnancy† 85 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

OVERALL SUMMARY 86

Clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle 2016 60 50 Percent per CS/embryo thaw cycle (%) 40 38 38 36 35 35 35 28 30 26 25 23 23 22 21 18 20 18 17 10 9 9 10 4 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL 87 * 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 2016 70 60 53 52 50 50 Percent per ET cycle (%) 43 41 38 38 40 37 36 36 36 33 33 31 31 28 30 25 24 20 19 20 10 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL 88 * Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Implantation rate 2016 60 50 44 40 40 Percent (%) 32 32 30 30 26 25 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 89 * 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 2016 60 53 50 47 44 40 36 35 33 Percent (%) 33 32 32 32 32 30 30 30 26 26 26 24 19 20 17 13 10 0 Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural FET – own oocytes* FET – donor oocytes IVF* <35 35 – 39 ≥40 OVERALL 90 * 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 2016 60 50 Percent per CS/embryo thaw cycle (%) 40 32 31 30 29 29 28 30 22 19 19 19 19 18 20 14 14 13 11 9 9 10 6 S 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 91 † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound S Numbers less than 6 were suppressed

Singleton ongoing clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle 2016 60 50 44 41 40 Percent per ET cycle (%) 40 35 32 31 30 30 30 29 29 30 28 27 26 24 22 20 20 15 12 10 S 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 92 S Numbers less than 6 were suppressed

CYCLES USING PGS 93

Proportion of utilizable embryos and clinical pregnancy for cycles with and without PGS IVF and FET, 2013, 2014, 2015, 2016 Cycles without PGS Cycles with PGS Number of embryos thawed 69,388 3,042 Number of utilizable embryos after thaw 59,999 2,827 Proportion of utilizable embryos after 86.5% 92.9% thaw Number of clinical pregnancies 31,567 1,194 Proportion of clinical pregnancies per 28.6% 20.2% cycle start Proportion of clinical pregnancies per ET 37.5% 44.3% cycle 94

PRIMARY TRANSFER RATE 95

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 96

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 97

Primary transfer clinical pregnancy rate, per patient IVF and FET, 2013, 2014, 2015 and 2016 100 80 Percent per primary transfer (%) 60 45.2 40.1 40 34.7 20 0 <35 ≥35 OVERALL Patient age (years) Clinical 11,163 8,192 19,355 pregnancy 98 * 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 and 2016 100 80 Percent per primary transfer (%) 60 45.8 40.1 39.7 40 20 0 Own Donor OVERALL Clinical 17,889 1,466 19,355 pregnancy 99 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Primary transfer clinical pregnancy rate, per patient with and without PGS IVF and FET, 2013, 2014, 2015 and 2016 100 80 Percent per primary transfer (%) 60 46.3 39.9 40.1 40 20 0 Excluding cycles with PGS Cycles with PGS OVERALL Clinical 18,697 658 19,355 pregnancy 100 * Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy