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

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Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus)

Canadian Fertility and Andrology Society

64th Annual Meeting – Montreal September 13 – 15, 2018

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List of abbreviations

CS Cycle start RET Oocyte retrieval ET Embryo transfer IVF In vitro fertilization FET Frozen embryo transfer PGT-A/PGT-M Preimplantation Genetic Testing for Aneuploidy/Monogenic (Single Gene) Diseases IVM In vitro maturation OHSS Ovarian hyperstimulation syndrome eSET Elective single embryo transfer neSET Non-elective single embryo transfer eDET Elective double embryo transfer neDET Non-elective double embryo transfer

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Disclaimer

• This report is based on data submitted by assisted

reproductive technology clinics from across Canada to the CARTR Plus database. Although significant effort has been made to ensure the accuracy of the information presented in this report, neither the authors nor BORN Ontario nor any

• ther parties make any representation or warranties as to the

accuracy, reliability or completeness of the information contained herein.

• Permission is granted for the reproduction of these materials

solely for non‐commercial and educational purposes.

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Suggested citations

Canadian Assisted Reproductive Technologies Registry (CARTR)

• Plus. Final treatment cycle and pregnancy outcome data for
• 2016. Better Outcomes Registry & Network Ontario. Ottawa

ON, September 2018. Canadian Assisted Reproductive Technologies Registry (CARTR)

• Plus. Preliminary treatment cycle data for 2017. Better

Outcomes Registry & Network Ontario. Ottawa ON, September 2018.

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Notes

• All data current as of July 2018
• Treatment cycle outcomes for 2017 cycle starts

– Based on 36 clinics

• Birth outcomes for 2016 cycle starts

– Based on 35 clinics

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Notes

• These slides present descriptive estimates on which no formal

statistical tests have been carried out; therefore, differences across treatment cycles, patient characteristics or embryo transfer characteristics may not be statistically significant and should be interpreted cautiously

• Unless otherwise specified, denominators for birth outcomes

are based on the pregnancy level

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INTRODUCTION

All ART treatment cycles (fresh and frozen)

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CARTR Plus records extracted July 2018

Total treatment records entered into CARTR Plus with a cycle start date between Jan 1, 2013 and Dec 31, 2017: n = 147,419

* Unacknowledged records were included if they were “submitted” or if they linked to an outcome

2013 Treatment cycles: n = 25,349 31 clinics

Birth outcomes 95.0% complete (8,406/8,850) per ongoing clinical pregnancy

35 clinics 2014 Treatment cycles: n = 28,166 34 clinics 2015 Treatment cycles: n = 29,538 33 clinics 2016 Treatment cycles: n = 31,274 35 clinics 2017 Treatment cycles: n = 33,092 36 clinics

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Number of Unique Women

All ART treatment cycles

17,051 18,424 18,914 20,644 21,271 25,349 28,166 29,538 31,274 33,092

10000 20000 30000 40000 2013 2014 2015 2016 2017

Unique Women Cycle Starts

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Volume of treatment cycles by clinic

All ART treatment cycles

5 7 11 7 30 6 7 11 7 31 6 7 10 11 34 6 6 13 8 33 2 9 12 11 34 2 9 12 13 36

5 10 15 20 25 30 35 40 <200 200–499 500–999 ≥1,000 TOTAL

Number of treatment cycles CARTR, 2012 CARTR Plus, 2013 CARTR Plus, 2014 CARTR Plus, 2015 CARTR Plus, 2016 CARTR Plus, 2017

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Number of cycles and clinical pregnancies

All ART treatment cycles

33,092 23,044 8,511 7,738

5,000 10,000 15,000 20,000 25,000 30,000 35,000 Cycle starts Embryo transfer cycles Clinical pregnancies* Ongoing clinical pregnancies†

CARTR, 2011 CARTR, 2012 CARTR Plus, 2013 CARTR Plus, 2014 CARTR Plus, 2015 CARTR Plus, 2016 CARTR Plus, 2017

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound

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Number of cycles and clinical pregnancies

All ART treatment cycles

23,997 19,811 7,030 6,368 25,782 21,054 7,714 6,982 25,349 19,785 7,727 7,716 28,166 20,886 8,250 8,245 29,538 21,500 8,583 7,756 31,274 22,637 8,779 7,940 33,092 23,044 8,511 7,738

5,000 10,000 15,000 20,000 25,000 30,000 35,000 Cycle starts Embryo transfer cycles Clinical pregnancies* Ongoing clinical pregnancies†

CARTR, 2011 CARTR, 2012 CARTR Plus, 2013 CARTR Plus, 2014 CARTR Plus, 2015 CARTR Plus, 2016

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound

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Number of multiple pregnancies

All ART treatment cycles

6,368 1,350 6,982 1,217 7,716 1,167 8,245 1,038 7,756 953 7,940 760 7,738 607

1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 Ongoing clinical pregnancies* Multiple pregnancies†

CARTR, 2011 CARTR, 2012 CARTR Plus, 2013 CARTR Plus, 2014 CARTR Plus, 2015 CARTR Plus, 2016 CARTR Plus, 2017

* Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

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Percentage of multiple pregnancies

All ART treatment cycles

21.2 17.4 15.1 12.6 12.3 9.6 7.9

5 10 15 20 25 30

CARTR, 2011 CARTR, 2012 CARTR Plus, 2013 CARTR Plus, 2014 CARTR Plus, 2015 CARTR Plus, 2016 CARTR Plus, 2017

Percent per ongoing clinical pregnancy (%)

Twin Triplet+

* Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

1,278 1,152 1,122 72 65 45 34 1,004 733 27 44 909 Twin Triplet + 595 12

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Percentage of multiple pregnancies in Ontario

All ART treatment cycles

18.8 14.0 13.2 7.6 6.1

5 10 15 20 25 30

CARTR Plus, 2013 CARTR Plus, 2014 CARTR Plus, 2015 CARTR Plus, 2016 CARTR Plus, 2017

Percent per ongoing clinical pregnancy (%)

Twin Triplet+

* Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

585 448 25 13 22 396 16 307 Twin Triplet + 246 4

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Specialized services

All ART treatment cycles (fresh and frozen), 2017

Description Number of cycles

Gestational carrier 895 PGT-A/PGT-M 5,422 Oocyte or embryo banking due to cancer treatment 264 Oocyte or embryo banking due to non-cancer/non-medical reasons 381 Any use of donor oocytes or embryos 3,297 Frozen oocyte IVF 674

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Oocyte or embryo freezing for non-medical reasons

2013, 2014, 2015, 2016, 2017

Year Number of cycles

2013 132 2014 174 2015 280 2016 332 2017 381 Overall 1,299

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PGT-A and PGT-M

2013, 2014, 2015, 2016, 2017

Year Number of cycles

2013 463 2014 864 2015 2,499 2016 4,444 2017 5,422 Overall 19,692

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TREATMENT CYCLES FOR 2017

All ART treatment cycles (fresh and frozen)

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Number of treatment cycles

2016

15,344 754 178 12,071 1,587 125 460 8,084 343 58 11,902 1,580 57 426

2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000

Fresh IVF – own

• ocytes*

Fresh IVF – donor

• ocytes

Natural/modified natural IVF* FET – own

• ocytes*

FET – donor

• ocytes

Frozen oocyte IVF – own oocytes* Frozen oocyte IVF – donor oocytes

Cycle starts / Embryo thaw cycles ET cycles

* Own oocytes exclusively

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Number of treatment cycles

2017

15,391 823 142 13,417 1,912 136 538 7,000 262 42 13,261 1,906 78 492

2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000

Fresh IVF – own

• ocytes*

Fresh IVF – donor

• ocytes

Natural/modified natural IVF* FET – own

• ocytes*

FET – donor

• ocytes

Frozen oocyte IVF – own oocytes* Frozen oocyte IVF – donor oocytes

Cycle starts / Embryo thaw cycles ET cycles

* Own oocytes exclusively

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Type of treatment cycle, per cycle start

All ART treatment cycles (fresh and frozen), 2017

0.0 2.2 2.0 46.3 49.0

20 40 60 80 IVM Oocyte banking Frozen oocyte IVF FET IVF Percent (%)

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Type of treatment cycle, per cycle start

All ART treatment cycles (fresh and frozen), 2017

0.04 2.2 1.6 0.4 5.8 40.5 0.4 2.5 46.5

0.00 20.00 40.00 60.00 80.00 IVM Oocyte banking Frozen oocyte IVF – donor oocytes Frozen oocyte IVF – own oocytes* FET – donor oocytes FET – own oocytes* Natural/modified natural IVF* Fresh IVF – donor oocytes Fresh IVF – own oocytes* Percent (%)

* Own oocytes exclusively

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Type of treatment cycle, per cycle start

All ART treatment cycles (fresh and frozen), 2017

Type of treatment cycle Number Percent

IVF – own oocytes* 15,391 46.51 IVF – donor oocytes 823 2.49 Natural/modified natural IVF* 142 0.43 FET – own oocytes* 13,417 40.54 FET – donor oocytes 1,912 5.78 Frozen oocyte IVF – own oocytes* 136 0.41 Frozen oocyte IVF – donor oocytes 538 1.63 Oocyte banking 721 2.18 IVM 12 0.04 TOTAL TREATMENT CYCLES 33,092

* Own oocytes exclusively

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Reasons for treatment

All ART treatment cycles (fresh and frozen), 2017

1.2 1.2 1.5 2.4 2.95 4.1 4.6 4.7 7.0 9.0 9.1 10.3 15.3 18.2 19.2 30.5

5 10 15 20 25 30 35 Oocyte/embryo banking for non-cancer/non-medical reasons Oocyte/embryo banking for cancer treatment PGT-M Other reasons† Other uterine factor No male partner Other female factor Other ovulatory disorder Endometriosis Tubal factor PCOS PGT-A Diminished ovarian reserve Advanced female age Unexplained infertility Male factor Percent per cycle start (%)

* Categories are not mutually exclusive † Other reasons include: gonadotoxic therapy, no female partner and peritoneal factor or severe adhesions

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Clinical pregnancy by type of treatment cycle

2017

15 17 8 37 41 21 42 33 52 26 38 41 36 46 10 20 30 40 50 60

Fresh IVF – own

• ocytes*

Fresh IVF – donor

• ocytes

Natural/modified natural IVF* FET – own oocytes* FET – donor

• ocytes

Frozen oocyte IVF –

• wn oocytes*

Frozen oocyte IVF – donor oocytes

Percent (%)

Per cycle start / embryo thaw cycle Per ET cycle

* Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Clinical pregnancies 2,320 136 11 782 28 225 5,009

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Singleton ongoing clinical pregnancy by type of treatment cycle

2017

12 13 8 32 35 16 36 27 42 26 32 35 28 39 10 20 30 40 50 60

Fresh IVF – own

• ocytes*

Fresh IVF – donor

• ocytes

Natural/modified natural IVF* FET – own

• ocytes*

FET – donor

• ocytes

Frozen oocyte IVF – own oocytes* Frozen oocyte IVF – donor oocytes

Percent (%)

Per cycle start / embryo thaw cycle Per ET cycle

* Own oocytes exclusively † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

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Patient age

All ART treatment cycles (fresh and frozen), 2017

39.1 23.5 20.1 9.9 7.3

10 20 30 40 50 60 <35 35–37 38–40 41–42 ≥43 Percent per cycle start (%)

Patient age (years)

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TREATMENT CYCLES FOR 2017

ART cycles using IVF – own oocytes

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Stage of treatment and treatment outcomes

ART cycles using IVF – own oocytes, 2017

15,391 14,542 7,000 2,320 2,112 1,902

2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 Cycle starts (CS) Oocyte retrieval cycles (RET) Embryo transfer cycles (ET) Clinical pregnancies* Ongoing clinical pregnancies† Singleton pregnancies‡

849 cancelled: 5.5% per CS 13.7% per CS 14.5% per RET 30.2% per ET 12.4% per CS 13.1% per RET 27.2% per ET 15.1% per CS 16.0% per RET 33.1% per ET

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † 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

7542 no ET: 48.1% per RET

90.1% of ongoing clinical pregnancies

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Stage of treatment and treatment outcomes

ART cycles using IVF – own oocytes, 2017

15,391 14,542 7,000 2,320 2,112 1,902

2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 Cycle starts (CS) Oocyte retrieval cycles (RET) Embryo transfer cycles (ET) Clinical pregnancies* Ongoing clinical pregnancies† Singleton pregnancies‡

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † 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

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Percentage of cancelled cycles

ART cycles using IVF – own oocytes, 2017

3.9 5.1 6.3 9.4 8.5 5.5

5 10 15 20 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per cycle start (%)

Patient age (years)

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Reasons for cycle cancellation

ART cycles using IVF – own oocytes, 2017

1.1 2.1 3.2 4.7 13.6 78.1

10 20 30 40 50 60 70 80 90 Patient personal reason Premature luteinization Patient error Premature ovulation Other reasons† Low ovarian response Percent per cancelled cycle (%)

* Categories are not mutually exclusive † Other reasons include: patient illness, donor illness, donor personal reason, donor error, no access to ovaries, other (unspecified)

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Percentage of cycles with no embryo transfer

ART cycles using IVF – own oocytes, 2017

51.3 50.7 51.9 52.9 61.8 51.9

10 20 30 40 50 60 70 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per oocyte retrieval cycle (%)

Patient age (years)

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Reasons for no embryo transfer

ART cycles using IVF – own oocytes, 2016

0.8 1.0 1.6 2.0 3.7 5.6 9.2 11.2 17.0 22.4 25.6

5 10 15 20 25 30 No sperm Inadequate uterine lining No utilizable oocytes No oocytes Freeze all, other reason than OHSS risk (unknown PGT) No normal fertilization Freeze all, PGT-M No utilizable embryos Freeze all, OHSS risk Freeze all, PGT-A Freeze all, other reason than OHSS risk or PGT Percent per oocyte retrieval cycle with no embryo transfer (%)

* Categories are mutually exclusive

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Reasons for no embryo transfer

ART cycles using IVF – own oocytes, 2017

0.4 0.9 1.5 1.7 4.8 4.9 5.2 11.7 18.3 24.8 26.0

5 10 15 20 25 30 No sperm Inadequate uterine lining No utilizable oocytes No oocytes Freeze all, other reason than OHSS risk (unknown PGT) No normal fertilization Freeze all, PGT-M No utilizable embryos Freeze all, OHSS risk Freeze all, PGT-A Freeze all, other reason than OHSS risk or PGT Percent per oocyte retrieval cycle with no embryo transfer (%)

* Categories are mutually exclusive

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Method of insemination

ART cycles using IVF – own oocytes, 2017

13.6 77.8 5.3 1.2 2.2

10 20 30 40 50 60 70 80 90 Conventional IVF only ICSI only Conventional IVF and ICSI Rescue ICSI Not done Percent per oocyte retrieval cycle (%)

Conventional IVF and ICSI: a single ET cycle used both conventional IVF and ICSI

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Number of embryos transferred

ART cycles using IVF – own oocytes, 2017

62.1 34.3 3.7

10 20 30 40 50 60 1 embryo 2 embryos ≥3 embryos Percent per ET cycle (%) eSET: 61.4% per ET=1

eSET eDET

eDET: 47.2% per ET=2

* 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

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Number of embryos transferred

ART cycles using IVF – own oocytes, 2017

80.3 19.4 0.3 57.7 39.9 2.3 34.9 52.3 12.8

10 20 30 40 50 60 70 80 1 embryo 2 embryos ≥3 embryos 1 embryo 2 embryos ≥3 embryos 1 embryo 2 embryos ≥3 embryos Percent per ET cycle (%)

eSET eDET eSET eSET eDET eDET <35 years 35–39 years ≥40 years Patient age (years)

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Embryo transfer day

ART cycles using IVF – own oocytes, 2017

4.2 31.6 0.4 62.9 1.0

10 20 30 40 50 60 70 Day 2 Day 3 Day 4 Day 5 Day 6 or 7 Percent per ET cycle (%)

* Excludes records with missing embryo transfer day

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Clinical pregnancy and implantation rate

ART cycles using IVF – own oocytes, 2017

39.0 36.9 28.1 19.5 10.7 33.1 34.8 30.5 20.0 13.0 6.2 25.9

10 20 30 40 50 60 <35 35–37 38–40 41–42 ≥43 OVERALL Percent (%)

Patient age (years)

Clinical pregnancy, per ET cycle Implantation rate

* 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

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Clinical pregnancy and implantation rate

ART cycles using IVF – own oocytes, 2017

33.8 33.2 21.4 33.1 34.2 21.2 8.7 25.9

10 20 30 40 50 60 1 2 ≥3 OVERALL Percent (%)

Number of embryos transferred

Clinical pregnancy, per ET cycle Implantation rate

* 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

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Clinical pregnancy and implantation rate by eSET/eDET

ART cycles using IVF – own oocytes, 2017

40.9 22.7 35.7 30.9 33.1 41.3 22.8 23.3 19.4 25.9

10 20 30 40 50 60 Elective single embryo transfer (eSET) Non-elective single embryo transfer Elective double embryo transfer (eDET) Non-elective double embryo transfer OVERALL Percent (%) 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 * 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

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Clinical pregnancy and implantation rate

ART cycles using IVF – own oocytes, 2017

26.3 37.8 33.1 18.3 31.7 25.9

10 20 30 40 50 60 Day 3 Day 5 OVERALL Percent (%)

Embryo transfer day

Clinical pregnancy, per ET cycle Implantation rate

* 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

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Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using IVF – own oocytes, 2017

36.5 33.3 25.2 16.6 6.5 30.2

10 20 30 40 50 60 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per ET cycle (%)

Patient age (years)

Singleton pregnancy Multiple pregnancy

* 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

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Percentage of multiple pregnancies

ART cycles using IVF – own oocytes, 2017

7.2 11.0 13.1 16.0 28.6 9.9

10 20 30 40 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per ongoing clinical pregnancy (%)

Patient age (years)

* Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Multiple pregnancies 74 62 50 20 4 210

S

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Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using IVF – own oocytes, 2017

31.8 23.9 15.2 30.2

10 20 30 40 50 60 1 2 ≥3 OVERALL Percent per ET cycle (%)

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 * 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

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Percentage of multiple pregnancies

ART cycles using IVF – own oocytes, 2017

1.7 25.2 20.4 9.9

10 20 30 40 1 2 ≥3 OVERALL Percent per ongoing clinical pregnancy (%)

Number of embryos transferred

Multiple pregnancies 23 177 10 210

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 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

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Proportion of cycles resulting in an ongoing clinical pregnancy by plurality and eSET/eDET

ART cycles using IVF – own oocytes, 2017

37.9 20.9 31.7 27.2 30.2

10 20 30 40 50 60 Elective single embryo transfer (eSET) Non-elective single embryo transfer Elective double embryo transfer (eDET) Non-elective double embryo transfer OVERALL Percent per ET cycle (%) 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 * 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

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Percentage of multiple pregnancies by eSET/eDET

ART cycles using IVF – own oocytes, 2017

2.0 0.9 27.1 23.2 9.9

10 20 30 40 Elective single embryo transfer (eSET) Non-elective single embryo transfer Elective double embryo transfer (eDET) Non-elective double embryo transfer OVERALL Percent per ongoing clinical 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 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Multiple pregnancies 20 3 97 80 210

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Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using IVF – own oocytes, 2017

23.9 34.5 30.2

10 20 30 40 50 60 Day 3 Day 5 OVERALL Percent per ET cycle (%)

Embryo transfer day

Singleton pregnancy Multiple pregnancy

* 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

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Percentage of multiple pregnancies

ART cycles using IVF – own oocytes, 2017

11.2 9.6 9.9

10 20 30 40 Day 3 Day 5 OVERALL Percent per ongoing clinical pregnancy (%)

Embryo transfer day

* Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Multiple pregnancies 59 145 210

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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)† Singleton‡ Multiple‡ 2,112 1,902 210 13.7 12.4 1.36 30.2 27.2 3.00 91.0 82.0 9.1 90.1 9.9 Multiple pregnancy‡ Twins Triplet or higher 210 207 3 1.36 3.00 9.1 9.9

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † 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

98.6% of multiple pregnancies were twin gestations

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Oocyte retrieval, embryo transfer, clinical pregnancy and singleton pregnancy

ART cycles using IVF – own oocytes, 2017

96 95 94 91 92 94 47 47 45 43 35 45 18 17 13 8 4 15 16 14 10 6 2 12 20 40 60 80 100 120 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per CS (%)

Patient age (years) Retrieval Embryo transfer Clinical pregnancy* Singleton pregnancy†

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

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TREATMENT CYCLES FOR 2017

ART cycles using FET – own oocytes

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Stage of treatment and treatment outcomes

ART cycles using FET – own oocytes, 2017

13,417 13,261 5,009 4,527 4,223

2,000 4,000 6,000 8,000 10,000 12,000 14,000 Embryo thaw cycles Embryo transfer cycles (ET) Clinical pregnancies* Ongoing clinical pregnancies† Singleton pregnancies‡

37.3% per thaw 37.8% per ET

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † 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

33.7% per thaw 34.1% per ET 31.5% per thaw 31.8% per ET 156 no ET: 1.2% per thaw

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Method of embryo cryopreservation

ART cycles using FET – own oocytes, 2017

96.8 3.1 0.1

20 40 60 80 100 Vitrification Slow freezing Mixed Percent per embryo thaw cycle (%)

58

Percentage of no embryo transfer

ART cycles using FET – own oocytes, 2017

1.1 1.0 1.1 2.1 4.6 1.2

2 4 6 8 10 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per embryo thaw cycle (%)

Age at time of oocyte retrieval (years)

59

Number of embryos transferred

ART cycles using FET – own oocytes, 2017

82.7 16.9 0.4

10 20 30 40 50 60 70 80 90 1 embryo 2 embryos ≥3 embryos Percent per ET cycle (%) eSET: 52.4% per ET=1

eSET eDET

eDET: 46.5% per ET=2

* 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

60

Number of embryos transferred

ART cycles using FET – own oocytes, 2017

87.0 12.8 0.1 80.9 18.8 0.3 66.7 31.6 1.6

10 20 30 40 50 60 70 80 90 1 embryo 2 embryos ≥3 embryos 1 embryo 2 embryos ≥3 embryos 1 embryo 2 embryos ≥3 embryos Percent per ET cycle (%) eSET eDET eSET eSET eDET eDET

<35 years 35–39 years ≥40 years Age at time of oocyte retrieval (years)

61

Clinical pregnancy and implantation rate

ART cycles using FET – own oocytes, 2017

40.9 38.3 31.2 26.1 19.9 37.8 38.7 35.0 26.7 20.4 14.8 34.4

10 20 30 40 50 <35 35–37 38–40 41–42 ≥43 OVERALL Percent (%)

Age at time of oocyte retrieval (years)

Clinical pregnancy, per ET cycle Implantation rate

* 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

62

Clinical pregnancy and implantation rate

ART cycles using FET – own oocytes, 2017

37.1 41.7 16.3 37.8 37.6 27.3 7.8 34.4

10 20 30 40 50 1 2 ≥3 OVERALL Percent (%)

Number of embryos transferred

Clinical pregnancy, per ET cycle Implantation rate

* 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

63

Clinical pregnancy and implantation rate by eSET/eDET

ART cycles using FET – own oocytes, 2017

41.7 32.0 44.0 39.6 37.8 42.4 32.4 29.0 25.9 34.4

10 20 30 40 50 Elective single embryo transfer (eSET) Non-elective single embryo transfer Elective double embryo transfer (eDET) Non-elective double embryo transfer OVERALL Percent (%) 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 * 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

64

Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using FET – own oocytes, 2017

37.1 34.8 27.7 22.7 17.2 34.1

10 20 30 40 50 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per ET cycle (%)

Age at time of oocyte retrieval (years)

Singleton pregnancy Multiple pregnancy

* 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

65

Percentage of multiple pregnancies

ART cycles using FET – own oocytes, 2017

6.8 6.0 8.3 5.4 6.3 6.7

10 20 30 40 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per ongoing clinical pregnancy (%)

Age at time of oocyte retrieval (years)

* Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Multiple pregnancies 181 66 47 8 2 304

66

Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using FET – own oocytes, 2017

33.6 37.0 16.3 34.1

10 20 30 40 50 1 2 ≥3 OVERALL Percent per ET cycle (%)

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 * 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

67

Percentage of multiple pregnancies

ART cycles using FET – own oocytes, 2017

1.7 28.5 50.0 6.7

10 20 30 40 50 60 1 2 ≥3 OVERALL Percent per ongoing clinical pregnancy (%)

Number of embryos transferred

Multiple pregnancies 64 236 4 304

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 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

68

Proportion of cycles resulting in an ongoing clinical pregnancy by plurality and eSET/eDET

ART cycles using FET – own oocytes, 2017

38.0 28.8 39.6 34.7 34.1

10 20 30 40 50 60 Elective single embryo transfer (eSET) Non-elective single embryo transfer Elective double embryo transfer (eDET) Non-elective double embryo transfer OVERALL Percent per ET cycle (%) 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 * 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

69

Percentage of multiple pregnancies by eSET/eDET

ART cycles using FET – own oocytes, 2017

1.6 2.0 28.6 28.4 6.7

10 20 30 40 Elective single embryo transfer (eSET) Non-elective single embryo transfer Elective double embryo transfer (eDET) Non-elective double embryo transfer OVERALL Percent per ongoing clinical 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 * Ongoing clinical pregnancy: clinical pregnancy with ≥1 fetal heart beat on ultrasound † Multiple pregnancy: ongoing clinical pregnancy with >1 fetal heart beat on ultrasound

Multiple pregnancies 34 30 118 118 304

70

Treatment outcomes

ART cycles using FET – own oocytes, 2017 Treatment outcome Number % per embryo thaw % per ET % per CP % per OCP Clinical pregnancy (CP)* 5,009 37.3 37.8 Ongoing clinical pregnancy (OCP)† Singleton‡ Multiple‡ 4,527 4,223 304 33.7 31.5 2.3 34.1 31.8 2.3 90.4 84.3 6.1 93.3 6.7 Multiple pregnancy‡ Twins Triplet or higher 304 297 7 2.5 2.5 7.1 7.9

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † 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

97.7% of multiple pregnancies were twin gestations

71

Embryo transfer, clinical pregnancy and singleton clinical pregnancy

ART cycles using FET – own oocytes, 2017

99 99 99 98 95 99 40 38 31 26 19 37 34 32 25 21 15 31 20 40 60 80 100 <35 35–37 38–40 41–42 ≥43 OVERALL Percent per embryo thaw cycle (%)

Age at time of oocyte retrieval (years) Embryo transfer Clinical pregnancy* Singleton pregnancy†

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

72

OVERALL SUMMARY

73

Clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle

2017

18 15 5 40 42 16 24 14 36 42 9 42 26 31 15 17 8 37 41 10 20 30 40 50 60

Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural IVF* FET – own oocytes* FET – donor oocytes

Percent per CS/embryo thaw cycle (%)

<35 35–39 ≥40 OVERALL

* Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

74

Clinical pregnancy by age at time of oocyte retrieval and type of treatment cycle

2017

39 52 25 41 43 34 51 38 36 42 21 56 27 31 33 52 26 38 41 10 20 30 40 50 60 70

Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural IVF* FET – own oocytes* FET – donor oocytes

Percent per ET cycle (%)

<35 35–39 ≥40 OVERALL

* Own oocytes exclusively † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

75

Implantation rate

2017

26 49 26 34 38 28 39 10 20 30 40 50 60

Fresh IVF – own

• ocytes*

Fresh IVF – donor

• ocytes

Natural/modified natural IVF* FET – own

• ocytes*

FET – donor

• ocytes

Frozen oocyte IVF – own oocytes* Frozen oocyte IVF – donor oocytes

Percent (%)

* Own oocytes exclusively † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

Type of treatment cycle

76

Implantation rate by age at time of oocyte retrieval and type

• f treatment cycle

2017

35 51 25 39 39 27 42 38 32 36 14 43 21 29 26 49 26 34 38 10 20 30 40 50 60

Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural IVF* FET – own oocytes* FET – donor oocytes

Percent (%)

<35 35–39 ≥40 OVERALL

* Own oocytes exclusively † Implantation rate: number of gestational sacs observed on ultrasound, divided by the total number of embryos transferred

77

Singleton ongoing clinical pregnancy by age at time of

• ocyte retrieval and type of treatment cycle

2017

16 12 5 34 37 13 20 14 30 35 6 33 21 25 12 13 8 32 35 10 20 30 40 50 60

Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural IVF* FET – own oocytes* FET – donor oocytes

Percent per CS/embryo thaw cycle (%)

<35 35–39 ≥40 OVERALL

* Own oocytes exclusively † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

78

Singleton ongoing clinical pregnancy by age at time of

• ocyte retrieval and type of treatment cycle

2017

34 42 25 35 37 27 41 38 31 36 15 44 22 25 27 42 26 32 35 10 20 30 40 50 60

Fresh IVF – own oocytes* Fresh IVF – donor oocytes Natural/modified natural IVF* FET – own oocytes* FET – donor oocytes

Percent per ET cycle (%)

<35 35–39 ≥40 OVERALL

* Own oocytes exclusively † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound

79

PRIMARY TRANSFER PREGNANCY RATE

80

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

81

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

82

Primary transfer clinical pregnancy rate per patient

IVF and FET, 2013, 2014, 2015, 2016 and 2017

45.5 35.0 40.4 20 40 60 80 100 <35 ≥35 OVERALL Percent per primary transfer (%) Patient age (years)

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Clinical pregnancy 13,623 9,947 23,570

83

Primary transfer clinical pregnancy rate per patient by

• ocyte type per patient

IVF and FET, 2013, 2014, 2015, 2016 and 2017

39.9 46.5 40.4 20 40 60 80 100 Own Donor OVERALL Percent per primary transfer (%)

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Clinical pregnancy 21,707 1,863 23,570

84

Primary transfer clinical pregnancy rate per patient with and without PGT-A

IVF and FET, 2013, 2014, 2015, 2016 and 2017

39.9 50.6 40.4 20 40 60 80 100 Excluding cycles with PGT-A Cycles with PGT-A OVERALL Percent per primary transfer (%)

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Clinical pregnancy 22,316 1,254 23,570

85

Primary transfer clinical pregnancy rate per batch of

• ocytes

IVF and FET, 2013, 2014, 2015, 2016 and 2017

46.8 34.4 39.7 20 40 60 80 100 <35 ≥35 OVERALL Percent per primary transfer (%) Patient age (years)

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Clinical pregnancy 12,021 11,899 23,920

86

Primary transfer clinical pregnancy rate per batch of

• ocytes with and without PGT-A

IVF and FET, 2013, 2014, 2015, 2016 and 2017

39.2 49.3 39.7 20 40 60 80 100 Excluding cycles with PGT-A Cycles with PGT-A OVERALL Percent per primary transfer (%)

* Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

Clinical pregnancy 22,506 1,414 23,920

87

CUMULATIVE PREGNANCY RATE

88

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

89

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

90

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

91

Cumulative pregnancy rate, per patient

All ART treatment cycles (fresh and frozen), 2013, 2014, 2015, 2016 and 2017

25.2 49.2 63.6 73.0 25.2 41.4 47.7 50.2 10 20 30 40 50 60 70 80 90 100 1 2 3 4 Probability of clinical pregnancy (%) Cycle number Optimistic Conservative

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.

92

Cumulative pregnancy rate, per batch of oocytes retrieved

IVF and FET – using own oocytes, 2013, 2014, 2015, 2016 and 2017

24.0 55.1 70.6 79.5 24.0 36.4 39.1 39.6 10 20 30 40 50 60 70 80 90 100 1 2 3 4 Probability of clinical pregnancy (%) Cycle number Optimistic Conservative

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.

93

Optimistic cumulative pregnancy rate, per batch of oocytes retrieved

IVF and FET – using own oocytes, 2013 ,2014, 2015, 2016 and 2017

29.4 61.1 75.9 83.6 20.4 49.7 65.0 74.7 10 20 30 40 50 60 70 80 90 100 1 2 3 4 Probability of clinical pregnancy (%) Cycle number <35 years ≥35 years

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.

94

Conservative cumulative pregnancy rate, per batch of oocytes retrieved

IVF and FET – using own oocytes, 2013, 2014, 2015, 2016 and 2017

29.4 45.9 49.9 50.8 20.4 29.8 31.6 32.0 10 20 30 40 50 60 70 80 90 100 1 2 3 4 Probability of clinical pregnancy (%) Cycle number <35 years ≥35 years

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. .

95

Cumulative pregnancy rate, per batch of oocytes retrieved

IVF and FET – using own oocytes, 2013, 2014, 2015, 2016 and 2017

29.4 61.1 75.9 83.6 20.4 49.7 65.0 74.7

20 40 60 80 100 Probability of clinical pregnancy (%)

Optimistic cumulative pregnancy rate

29.4 45.9 49.9 50.8 20.4 29.8 31.6 32.0

20 40 60 80 100 1 2 3 4 Probability of clinical pregnancy (%)

Cycle number

Conservative cumulative pregnancy rate

<35 years ≥35 years

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.

96

Cumulative pregnancy rate, per batch of oocytes retrieved

PGT-A/PGT-M – IVF and FET – using own oocytes 2013, 2014, 2015, 2016 and 2017

2.7 52.8 72.0 82.3 2.7 27.4 31.0 31.7 10 20 30 40 50 60 70 80 90 100 1 2 3 4 Probability of clinical pregnancy (%) Cycle number Optimistic Conservative

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.

97

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

5.0 54.6 73.5 83.6 5.0 51.3 58.2 59.5 10 20 30 40 50 60 70 80 90 100 1 2 3 4 Probability of clinical pregnancy (%) Cycle number Optimistic Conservative

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.

98

BIRTH OUTCOMES FOR 2016

All ART treatment cycles (fresh and frozen)

99

Birth outcomes

All ART treatment cycles (fresh and frozen), 2016

6,514 5,957 5,070

1,000 2,000 3,000 4,000 5,000 6,000 7,000 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 † Cycle starts, oocyte retrievals/thaws and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

100

Birth outcome rates

All ART treatment cycles (fresh and frozen), 2016

* Good perinatal outcome: singleton live birth at ≥37 weeks’ gestation and a birth weight ≥2,500 grams 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)

21.5 22.1 29.4 77.5 19.6 20.2 26.8 70.9 16.7 17.2 22.8 60.3

20 40 60 80 100 Per CS Per RET/THAW Per ET Per OCP Percent (%)

Live birth Singleton live birth Live birth Good perinatal outcome*

101

Distribution of birth outcomes among ongoing clinical pregnancies

ART cycles using IVF and FET – own oocytes, 2013

Singleton live birth 64.1% Multiple live birth 12.2% Stillbirth 0.9% Miscarriage 18.2% Unknown 4.6% Singleton live birth 64.2% Multiple live birth 9.6% Stillbirth 0.7% Miscarriage 20.4% Unknown 5.1%

IVF – own oocytes n= 4,176 FET – own oocytes n= 2,593

102

Distribution of birth outcomes among ongoing clinical pregnancies

ART cycles using IVF and FET – own oocytes, 2015

Singleton live birth 66.6% Multiple live birth 8.9% Stillbirth 0.7% Miscarriage 19.0% Unknown 4.7% Singleton live birth 65.5% Multiple live birth 7.2% Stillbirth 0.8% Miscarriage 21.4% Unknown 5.2%

IVF – own oocytes n= 3,771 FET – own oocytes n= 3,726

103

Distribution of birth outcomes among ongoing clinical pregnancies

ART cycles using IVF and FET – own oocytes, 2016

Singleton live birth 68.6% Multiple live birth 7.7% Stillbirth 1.0% Miscarriage 20.0% Unknown 2.8% Singleton live birth 67.4% Multiple live birth 5.2% Stillbirth 0.7% Miscarriage 21.2% Unknown 5.5%

IVF – own oocytes n= 2,942 FET – own oocytes n= 4,818

104

Birth outcome rates

ART cycles using IVF – own oocytes, 2016

44 38 31 19 10 36 30 21 11 3 33 26 18 10 3 27 23 15 8 3 10 20 30 40 50 60

<35 35–37 38–40 41–42 ≥43

Percent per ET cycle (%) Patient age (years)

Ongoing clinical pregnancy 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

105

Birth outcome rates

ART cycles using FET – own oocytes, 2016

43 41 38 24 26 32 29 25 15 13 30 27 23 14 13 26 24 20 12 11 10 20 30 40 50 60

<35 35–37 38–40 41–42 ≥43

Percent per ET cycle (%) Age at time of oocyte retrieval (years)

Ongoing clinical pregnancy 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

106

Proportion of miscarriages and stillbirths

ART cycles using IVF – own oocytes, 2016

35.7 6.5 0.42 27.1 7.3 0.31 11.9 8.5 0.25 27.6 7.2 0.34 10 20 30 40 50

Live birth MiscarriageƗ Stillbirth*

Percent per ET cycle (%)

<35 35–39 ≥40 OVERALL

* 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

Patient age (years)

107

Proportion of miscarriages and stillbirths

ART cycles using FET – own oocytes, 2016

32.4 7.8 0.37 28.5 9.2 0.19 16.4 9.7 0.07 29.2 8.5 0.28 10 20 30 40 50

Live birth MiscarriageƗ Stillbirth*

Percent per ET cycle (%)

<35 35–39 ≥40 OVERALL

* 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

Age at time of oocyte retrieval (years)

108

Percentage of birth outcomes by method of insemination

ART cycles using IVF – own oocytes, 2016

40.6 35.7 36.0 31.0 27.1 29.3 26.7 24.5 28.0 20.9 20.7 24.3 10 20 30 40 50 Conventional IVF only ICSI only Conventional IVF and ICSI Percent per ET cycle (%) Ongoing clinical pregnancy 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 † Conventional IVF and ICSI: a single ET cycle used both conventional IVF and ICSI

109

Proportion of singleton and multiple live births

Baby level - All ART treatment cycles (fresh and frozen), 2016

97.0 58.5 66.2 3.0 40.8 33.8 0.73 0.0 20 40 60 80 100 1 embryo 2 embryos ≥3 embryos Percent (%) Singleton live birth Twin live birth Triplet+ live birth

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

Live births 4,627 1,279 51

110

Proportion of preterm births by plurality

Baby level - All ART treatment cycles (fresh and frozen), 2016

10 58 10 64 9 63 15 59 20 40 60 80 100

Singleton Multiple

Percent per live birth (%)

Fresh IVF – own oocytes* Fresh IVF – donor oocytes FET – own oocytes* FET – donor oocytes

* Own oocytes exclusively Preterm birth <37 weeks’ gestation Total number of live births were used as the denominator for these calculations.

111

Birth outcomes by province

All ART treatment cycles (fresh and frozen), 2016

20 20 26 18 20 22 16 17 18 10 20 30 40 50 Ontario Quebec Rest of Canada Percent per cycle start (%)

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 Cycle starts, and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

112

Birth outcomes by province

All ART treatment cycles (fresh and frozen), 2016

29 25 34 27 24 29 23 21 24 10 20 30 40 50 Ontario Quebec Rest of Canada Percent per ET cycle (%)

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 Cycle starts, and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

113

Percentage of multiple live births by province

Baby level - All ART treatment cycles (fresh and frozen), 2016

12.6 4.4 23.7 15.3

10 20 30 40 Ontario Quebec Rest of Canada OVERALL Percent per live birth (%)

Ongoing clinical pregnancy: documentation of at least one fetal heart beat on ultrasound Multiple birth: At least one live birth from a multiple pregnancy

Multiple births 48 600 1,076 428

114

BIRTH OUTCOME TRENDS

All ART treatment cycles (fresh and frozen) 2013-2016

115

Proportion of live births

ART cycles using IVF – own oocytes, 2013-2016

41.1 30.0 13.8 40.9 30.9 12.3 39.5 29.5 13.4 35.7 27.1 11.9 10 20 30 40 50

<35 35–39 ≥40

Percent per ET cycle (%)

2013 2014 2015 2016

* 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

Age at time of oocyte retrieval (years)

116

Proportion of live births

ART cycles using FET – own oocytes, 2013-2016

30.9 26.1 15.8 33.6 27.1 15.9 32.3 27.7 17.5 33.0 29.2 18.6 10 20 30 40

<35 35–39 ≥40

Percent per ET cycle (%)

2013 2014 2015 2016

* 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

Age at time of oocyte retrieval (years)

117

Proportion of stillbirth rates

ART cycles using IVF – own oocytes, 2013-2016

0.48 0.38 0.13 0.37 0.26 0.14 0.33 0.31 0.22 0.42 0.31 0.25 0.0 0.2 0.4 0.6 0.8 1.0

<35 35–39 ≥40

Percent per ET cycle (%)

2013 2014 2015 2016

* 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

Age at time of oocyte retrieval (years)

118

Proportion of stillbirth rates

ART cycles using FET – own oocytes, 2013-2016

0.18 0.28 0.37 0.36 0.24 0.07 0.40 0.23 0.27 0.38 0.23 0.11 0.0 0.2 0.4 0.6 0.8 1.0

<35 35–39 ≥40

Percent per ET cycle (%)

2013 2014 2015 2016

* 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

Age at time of oocyte retrieval (years)

119

Proportion of singleton and multiple live births

All ART treatment cycles, 2013-2016

23.4 22.5 22.2 21.5

10 20 30 40

2013 2014 2015 2016

Percent per CS (%)

Multiple Live Births Singleton Live Births

† Cycle starts, oocyte retrievals/thaws and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

5,800 6,215 6,379 Live Births Singletons Multiples 6,514 4,932 5,413 5,658 5,957 868 802 721 557

120

Proportion of singleton and multiple live births

All ART treatment cycles, 2013-2016

29.8 30.2 30.3 29.4

10 20 30 40

2013 2014 2015 2016

Percent per ET cycle (%)

Multiple Live Births Singleton Live Births

† Cycle starts, oocyte retrievals/thaws and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

5,800 6,215 6,379 6,514 4,932 5,413 5,658 5,957 Live Births Singletons Multiples 868 802 721 557

121

Proportion of singleton and multiple live births by province

All ART treatment cycles, 2013-2016

23.7 22.9 21.4 19.5 16.8 17.9 18.9 19.7 30.8 27.0 26.1 25.1 10 20 30 40

2013 2014 2015 2016 2013 2014 2015 2016 2013 2014 2015 2016

Percent per CS (%)

Multiple Live Births Singleton Live Births

Ontario Quebec Rest of Canada

† Cycle starts, oocyte retrievals/thaws and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

122

Proportion of singleton and multiple live births by province

All ART treatment cycles, 2013-2016

29.7 30.0 30.0 28.6 24.6 27.3 27.1 24.9 35.7 33.8 34.0 33.6 10 20 30 40

2013 2014 2015 2016 2013 2014 2015 2016 2013 2014 2015 2016

Percent per ET cycle (%)

Multiple Live Births Singleton Live Births

Ontario Quebec Rest of Canada

† Cycle starts, oocyte retrievals/thaws and embryo transfers with an unknown birth outcome were removed from the denominator (n=444)

123

CUMULATIVE LIVE BIRTH RATE

124

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+

Cumulative live birth rate

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

125

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+ Ontario Rest of Canada All of Canada

Cumulative live birth rate

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

126

10 20 30 40 50 60 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Cumulative live birth rate

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

127

10 20 30 40 50 60 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Cumulative live birth rate

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

Ontario Rest of Canada All of Canada

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

128

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+

Cumulative live birth rate within one year of retrieval

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

129

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+ Ontario Rest of Canada All of Canada

Cumulative live birth rate within one year of retrieval

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

130

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Cumulative live birth rate within one year of retrieval

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

131

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Cumulative live birth rate within one year of retrieval

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

Ontario Rest of Canada All of Canada

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

132

PRIMARY TRANSFER LIVE BIRTH RATE

133

5 10 15 20 25 30 35 40 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+

Live birth rate for primary embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

134

5 10 15 20 25 30 35 40 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+ Ontario Rest of Canada All of Canada

Live birth rate for primary embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

135

5 10 15 20 25 30 35 40 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Live birth rate for primary embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

136

5 10 15 20 25 30 35 40 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Live birth rate for primary embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

Ontario Rest of Canada All of Canada

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

137

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+

Live birth rate for subsequent embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

138

5 10 15 20 25 30 35 40 45 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Singletons Twins Triplets+ Ontario Rest of Canada All of Canada

Live birth rate for subsequent embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes

139

2 4 6 8 10 12 14 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Live birth rate for subsequent embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

140

2 4 6 8 10 12 14 16 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43 <35 35-37 38-40 41-42 ≥43

% per CS

Term Preterm Very Preterm

Live birth rate for subsequent embryo transfer cycle

All ART treatment cycles (fresh and frozen) own oocytes, 2013-2016

Ontario Rest of Canada All of Canada

*Per batch of oocytes *Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Very preterm birth is defined as live birth or stillbirth at ≤32 weeks gestation.

141

PREGNANCY AND BIRTH OUTCOMES

ART vs. Non-ART − Ontario

142

Birth outcomes

ART vs. Non-ART Ontario – 2013, 2014, 2015, 2016

Total births ART Non-ART RR (95% CI)

• Adj. RR

(95%CI) n % n % Live birth

654,712 10,651 99.0 644,061 99.4 0.99 (0.99-1.00) 0.99 (0.99-1.00)

Stillbirth

4,264 109 1.01 4,155 0.64 1.44 (1.19-1.75) 1.58 (1.30-1.91)

* Adjusted for maternal age at delivery. Live birth defined as all births are live births. Stillbirth defined as any stillbirth.

143

Preterm birth

ART vs. Non-ART Ontario – 2013, 2014, 2015, 2016

• Preterm birth:

– <37 weeks’ gestation – RR = 2.25 95% CI: 2.16−2.36 – adjusted RR = 2.14 95% CI: 2.05−2.24

• Singleton preterm births:

– <37 weeks’ gestation – RR = 1.70 95% CI: 1.60−1.80 – adjusted RR = 1.63 95% CI: 1.54−1.73

* Adjusted for maternal age at delivery.

144

Preterm birth in Ontario

ART vs. Non-ART Ontario – 2013, 2014, 2015, 2016

*Preterm birth is defined as live birth or stillbirth at ≤37 weeks gestation. *Error bars represent 95% Confidence Intervals

1 1.5 2 2.5

Relative Risk Adjusted for Maternal Age at Delivery Unadjusted Adjusted for Maternal Age at Delivery Unadjusted All Preterm Births Singleton Preterm Births

145

Gestational age at time of delivery

ART vs. Non-ART Ontario – 2013, 2014, 2015, 2016

Gestational age at delivery Total births ART Non-ART RR (95% CI)

• Adj. RR

(95%CI) n % n % <32 weeks

9,769 382 3.55 9,387 1.45 2.45 (2.22-2.71) 2.25 (2.03-2.50)

32 weeks

2,087 91 0.85 1,996 0.31 2.75 (2.23-3.39) 2.63 (2.13-3.28)

33 weeks

3,192 152 1.41 3,040 0.47 3.01 (2.56-3.54) 2.87 (2.43-3.39)

34 weeks

5,697 233 2.17 5,464 0.84 2.57 (2.26-2.92) 2.43 (2.13-2.77)

35 weeks

9,578 331 3.08 9,247 1.43 2.16 (1.93-2.40) 2.10 (1.88-2.35)

36 weeks

19,408 607 5.64 18,801 2.90 1.94 (1.80-2.10) 1.87 (1.72-2.02)

≥37 weeks

609,219 8,964 83.31 600,255 92.60 0.90 (0.89-0.91) 0.90 (0.90-0.91)

* Adjusted for maternal age at delivery.

146

Gestational age at time of delivery for singleton pregnancies

ART vs. Non-ART Ontario – 2013, 2014, 2015, 2016

Gestational age at delivery Total births ART Non-ART RR (95% CI)

• Adj. RR

(95%CI) n % n % <32 weeks

8,717 256 2.69 8,461 1.33 2.03 (1.80-2.30) 1.87 (1.65-2.12)

32 weeks

1,737 57 0.60 1,680 0.26 2.28 (1.75-2.97) 2.17 (1.66-2.84)

33 weeks

2,662 75 0.79 2,587 0.41 1.95 (1.55-2.45) 1.84 (1.46-2.32)

34 weeks

4,859 118 1.24 4,741 0.74 1.67 (1.39-2.00) 1.60 (1.33-1.92)

35 weeks

8,348 191 2.01 8,157 1.28 1.57 (1.36-1.81) 1.56 (1.35-1.80)

36 weeks

17,186 376 3.96 16,810 2.63 1.50 (1.36-1.66) 1.47 (1.33-1.63)

≥37 weeks

604,076 8,427 88.71 595,649 93.35 0.94 (0.94-0.96) 0.95 (0.95-0.96)

* Adjusted for maternal age at delivery.

147

CLOSING REMARKS

148

Key messages

• Continuing to decrease the multiple pregnancy rate

– Increase in the proportion of single embryo transfers

• Increased proportion:

– freeze all cycles – PGT

149

THANK YOU!

• Dr. Andrea Lanes, Clinical Content Specialist

alanes@bornontario.ca Moya Johnson, Coordinator – CARTR Plus mojohnson@bornontario.ca Cathy Yang, Senior Data Analyst cyang@bornontario.ca Lynn Meng, Data Analyst lmeng@bornontario.ca Shelley Dougan, Manager sdougan@bornontario.ca