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

63rd Annual Meeting – Vancouver September 14 – 16, 2017

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CARTR Plus presentation outline

• Introduction of ART treatment cycles 2011─2016
• Birth outcomes ─ 2015
• All ART treatment cycles ─ 2016
• Primary transfer rate
• Cumulative pregnancy rate
• Ontario ART and Non-ART pregnancy and birth outcomes

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List of abbreviations

CS Cycle start RET Oocyte retrieval ET Embryo transfer IVF In vitro fertilization FET Frozen embryo transfer PGS/PGD Preimplantation genetic screening/diagnosis 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
• 2015. Better Outcomes Registry & Network Ontario. Ottawa

ON, September 2017. Canadian Assisted Reproductive Technologies Registry (CARTR)

• Plus. Preliminary treatment cycle data for 2016. Better

Outcomes Registry & Network Ontario. Ottawa ON, September 2017.

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Notes

• All data current as of June 2017.
• Treatment cycle outcomes for 2016 cycle starts

– Based on 34 clinics

• Birth outcomes for 2015 cycle starts

– Based on 33 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 June 2017

Total treatment records entered into CARTR Plus with a cycle start date between Jan 1, 2013 and Dec 31, 2016: n = 114,227

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

2014 Treatment cycles: n = 28,166 2015 Treatment cycles: n = 29,538 33 clinics

Birth outcomes 94.8% complete (8,193/8,641) per ongoing clinical pregnancy

34 clinics 2013 Treatment cycles: n = 25,349 31 clinics 33 clinics 2016 Treatment cycles: n = 31,174 34 clinics

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Number of Unique Women

All ART treatment cycles

17051 18424 18914 20549 25349 28116 29538 31174

10000 20000 30000 40000 2013 2014 2015 2016

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

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

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Number of cycles and clinical pregnancies

All ART treatment cycles

31174 22460 7927 7170

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 cycles and clinical pregnancies

All ART treatment cycles

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

23997 19811 7030 6368 25,782 21054 7714 6982 25349 19785 7727 7717 28166 20886 8250 8245 29538 21500 8583 7756 31174 22460 7927 7170

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

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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 7,435 953 7,170 697

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

* 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 9.7

5 10 15 20 25 30 CARTR, 2011 CARTR, 2012 CARTR Plus, 2013 CARTR Plus, 2014 CARTR Plus, 2015 CARTR Plus, 2016 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 1,004 671 26 44 909 Twin Triplet +

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BIRTH OUTCOMES FOR 2015

All ART treatment cycles (fresh and frozen)

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Birth outcomes

All ART treatment cycles (fresh and frozen), 2015

6,379 5,658 4,776

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=353)

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Birth outcome rates

All ART treatment cycles (fresh and frozen), 2015

* 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=353)

22.2 23.2 30.3 77.9 19.7 20.3 26.9 69.1 16.6 17.4 22.7 58.3

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*

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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

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Distribution of birth outcomes among ongoing clinical pregnancies

ART cycles using IVF and FET – own oocytes, 2014

Singleton live birth 66.1% Multiple live birth 10.6% Stillbirth 0.7% Miscarriage 18.7% Unknown 3.8% Singleton live birth 65.6% Multiple live birth 8.1% Stillbirth 0.7% Miscarriage 22.2% Unknown 3.5%

IVF – own oocytes n= 4,022 FET – own oocytes n= 3,281

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Birth outcome rates

ART cycles using IVF – own oocytes, 2015

48 43 34 23 15 40 33 22 12 8 35 29 19 10 6 30 24 16 9 6 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

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Birth outcome rates

ART cycles using FET – own oocytes, 2015

42 39 34 26 20 31 29 22 15 13 28 26 20 14 12 24 22 17 12 9 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

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Proportion of miscarriage and stillbirth rates

ART cycles using IVF – own oocytes, 2015

39.5 6.5 0.33 29.5 8.2 0.31 13.4 9.3 0.22 30.6 7.7 0.30 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)

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Proportion of miscarriage and stillbirth rates

ART cycles using FET – own oocytes, 2015

31.3 8.3 0.34 27.3 8.2 0.27 15.0 8.5 0.30 28.2 8.3 0.31 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)

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Percentage of birth outcomes by method of insemination

ART cycles using IVF – own oocytes, 2015

44.0 37.2 47.8 35.7 29.2 38.6 31.2 25.6 36.6 25.5 21.9 32.7 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

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Proportion of singleton and multiple live births

Baby level - All ART treatment cycles (fresh and frozen), 2015

96.8 57.4 58.6 3.2 41.4 35.4 1.25 6.06 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 4,067 2,798 198

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Proportion of preterm births by plurality

Baby level - All ART treatment cycles (fresh and frozen), 2015

10 60 10 59 10 62 16 48 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.

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Birth outcomes by province

All ART treatment cycles (fresh and frozen), 2015

22 19 27 19 18 22 16 16 19 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=353)

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Birth outcomes by province

All ART treatment cycles (fresh and frozen), 2015

30 27 34 26 26 29 22 22 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=353)

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Percentage of multiple live births by province

Baby level - All ART treatment cycles (fresh and frozen), 2015

22.5 5.2 28.0 19.9

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 97 708 1,405 600

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TREATMENT CYCLES FOR 2016

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

2015

15,273 722 956 9,526 1,229 83 417 9,075 479 331 9,251 1,233 51 383

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), 2016

0.1 2.0 1.9 43.8 51.6

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), 2016

0.1 2.0 1.5 0.4 5.1 38.7 0.6 2.4 49.2

20 40 60 80 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), 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

* Own oocytes exclusively

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Reasons for treatment

All ART treatment cycles (fresh and frozen), 2016

1.0 1.2 1.7 2.9 3.4 4.5 4.8 7.0 8.4 8.9 9.0 14.3 18.0 19.7 30.4

5 10 15 20 25 30 35 Oocyte/embryo banking for non-cancer/non-medical reasons Oocyte/embryo banking for cancer treatment Other reasons† Other uterine factor No male partner Other female factor Other ovulatory disorder Endometriosis PCOS PGS/PGD Tubal factor 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

2016

17 23 10 35 35 14 43 33 50 31 36 36 32 47 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 2,681 172 18 561 18 199 4,276

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Singleton ongoing clinical pregnancy by type of treatment cycle

2016

14 19 9 29 30 11 31 27 41 28 30 30 25 34 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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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

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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

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Patient age

All ART treatment cycles (fresh and frozen), 2016

38.8 23.5 20.3 10.2 7.2

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 2016

ART cycles using IVF – own oocytes

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Stage of treatment and treatment outcomes

ART cycles using IVF – own oocytes, 2016

15,344 14,606 8,084 2,681 2,438 2,152

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‡

738 cancelled: 4.8% per CS 21.6% per CS 23.1% per RET 36.4% per ET 15.9% per CS 16.7% per RET 30.2% per ET 17.5% per CS 18.4% per RET 33.2% 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

6522 no ET: 44.7% per RET

88.3% of ongoing clinical pregnancies

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Stage of treatment and treatment outcomes

ART cycles using IVF – own oocytes, 2016

15,344 14,606 8,084 2,681 2,438 2,152

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, 2016

3.6 4.7 5.8 6.4 7.8 4.8

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, 2016

1.4 2.3 0.7 1.8 3.1 16.1 77.5

10 20 30 40 50 60 70 80 90 Premature luteinization Patient error High ovarian response Patient personal reason 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, 2016

42.3 42.7 46.5 49.2 56.3 44.7

10 20 30 40 50 60 <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 PGS/PGD) No normal fertilization Freeze all, PGD No utilizable embryos Freeze all, OHSS risk Freeze all, PGS Freeze all, other reason than OHSS risk or PGS/PGD Percent per oocyte retrieval cycle with no embryo transfer (%)

* Categories are mutually exclusive

50

Reasons for no embryo transfer

ART cycles using IVF – own oocytes, 2015

0.7 0.7 1.6 2.9 5.9 6.0 6.8 9.4 15.7 18.0 32.4

5 10 15 20 25 30 35 Inadequate uterine lining No sperm No utilizable oocytes No oocytes Freeze all, PGS Freeze all, other reason than OHSS risk or PGS/PGD Freeze all, PGD No normal fertilization No utilizable embryos Freeze all, OHSS risk Freeze all, other reason than OHSS risk (unknown PGS/PGD) 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, 2016

13.2 76.8 4.5 3.1 2.5

10 20 30 40 50 60 70 80 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, 2016

59.2 36.7 4.1

10 20 30 40 50 60 1 embryo 2 embryos ≥3 embryos Percent per ET cycle (%) eSET: 59.5% per ET=1

eSET eDET

eDET: 43.7% 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, 2016

77.1 22.3 0.7 54.5 42.5 3.0 32.2 54.8 13.0

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, 2016

4.5 35.21 0.46 58.66 1.15

• 5

5 15 25 35 45 55 65 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, 2016

40.4 34.7 29.1 17.1 9.9 33.2 35.3 29.5 20.5 11.2 4.9 25.7

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, 2016

33.7 33.2 24.7 33.2 34.4 21.4 10.3 25.7

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, 2016

40.2 24.3 34.4 32.3 33.2 41.0 24.7 22.1 20.9 25.7

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

58

Clinical pregnancy and implantation rate

ART cycles using IVF – own oocytes, 2016

25.9 39.2 33.2 12.8 17.4 25.7

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

59

Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using IVF – own oocytes, 2016

37.6 31.9 25.6 13.5 7.0 30.1

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

60

Percentage of multiple pregnancies

ART cycles using IVF – own oocytes, 2016

8.5 14.7 16.4 13.7 5.9 11.7

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 S Numbers less than 6 were suppressed

Multiple pregnancies 105 91 73 16 S 286

S

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Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using IVF – own oocytes, 2016

31.1 29.9 19.2 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

62

Percentage of multiple pregnancies

ART cycles using IVF – own oocytes, 2016

2.2 26.6 27.0 11.7

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

Number of embryos transferred

Multiple pregnancies 33 236 17 286

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

63

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

ART cycles using IVF – own oocytes, 2016

37.1 22.2 31.0 29.0 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

64

Percentage of multiple pregnancies by eSET/eDET

ART cycles using IVF – own oocytes, 2016

2.2 2.3 27.1 26.2 11.7

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 23 10 109 127 286

65

Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using IVF – own oocytes, 2016

24.0 35.5 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

66

Percentage of multiple pregnancies

ART cycles using IVF – own oocytes, 2016

17.5 9.6 11.7

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 119 161 286

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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)† Singleton‡ Multiple‡ 2,438 2,152 286 15.9 14.0 1.86 30.2 26.7 3.53 90.9 10.6 80.3 88.3 11.7 Multiple pregnancy‡ Twins Triplet or higher 286 274 12 1.86 3.54 10.7 11.7

* 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

95.8% 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, 2016

96 95 94 94 92 95 56 55 50 48 40 53 22 19 15 8 4 17 19 15 11 6 3 14 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

69

TREATMENT CYCLES FOR 2016

ART cycles using FET – own oocytes

70

Stage of treatment and treatment outcomes

ART cycles using FET – own oocytes, 2016

12,071 11,902 4,276 3,836 3,534

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‡

35.4% per thaw 35.9% 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

31.8% per thaw 32.2% per ET 29.3% per thaw 29.7% per ET 169 no ET: 1.4% per thaw

71

Percentage of no embryo transfer

ART cycles using FET – own oocytes, 2016

1.5 1.2 1.1 1.3 3.2 1.4

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)

72

Number of embryos transferred

ART cycles using FET – own oocytes, 2016

79.1 20.2 0.7

10 20 30 40 50 60 70 80 1 embryo 2 embryos ≥3 embryos Percent per ET cycle (%) eSET: 50.1% per ET=1

eSET eDET

eDET: 45.1% 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

73

Number of embryos transferred

ART cycles using FET – own oocytes, 2016

84.1 15.6 0.3 77.1 22.3 0.6 62.1 35.0 2.9

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)

74

Method of embryo cryopreservation

ART cycles using FET – own oocytes, 2016

94.3 5.6 0.1

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

75

Clinical pregnancy and implantation rate

ART cycles using FET – own oocytes, 2016

38.3 36.3 33.6 21.8 22.4 35.9 35.8 32.9 27.5 16.7 16.1 32.1

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

76

Clinical pregnancy and implantation rate

ART cycles using FET – own oocytes, 2016

35.2 39.0 29.4 35.9 35.8 26.0 12.1 32.1

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

77

Clinical pregnancy and implantation rate by eSET/eDET

ART cycles using FET – own oocytes, 2016

36.8 33.6 39.3 38.7 35.9 37.5 34.1 26.1 25.9 32.1

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

78

Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using FET – own oocytes, 2016

34.8 32.5 29.3 18.5 17.6 32.2

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

79

Percentage of multiple pregnancies

ART cycles using FET – own oocytes, 2016

8.0 7.6 8.2 6.8 5.4 7.9

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 S Numbers less than 6 were suppressed

Multiple pregnancies 178 70 44 8 S 302

80

Proportion of cycles resulting in an ongoing clinical pregnancy

ART cycles using FET – own oocytes, 2016

31.7 34.4 28.2 32.2

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

81

Percentage of multiple pregnancies

ART cycles using FET – own oocytes, 2016

1.9 29.0 25.0 7.9

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

Number of embryos transferred

Multiple pregnancies 57 239 6 302

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

82

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

ART cycles using FET – own oocytes, 2016

33.6 29.9 34.6 34.2 32.2

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

83

Percentage of multiple pregnancies by eSET/eDET

ART cycles using FET – own oocytes, 2016

1.8 2.1 30.1 28.0 7.9

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 28 29 113 126 302

84

Treatment outcomes

ART cycles using FET – own oocytes, 2016 Treatment outcome Number % per embryo thaw % per ET % per CP % per OCP Clinical pregnancy (CP)* 4,276 35.4 35.9 Ongoing clinical pregnancy (OCP)† Singleton‡ Multiple‡ 3,836 3,534 302 31.8 29.3 2.5 32.2 29.7 2.5 89.7 82.6 7.1 92.1 7.9 Multiple pregnancy‡ Twins Triplet or higher 302 292 10 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

96.7% of multiple pregnancies were twin gestations

85

Embryo transfer, clinical pregnancy and singleton clinical pregnancy

ART cycles using FET – own oocytes, 2016

98 99 99 99 97 99 38 36 33 22 22 35 32 30 27 17 16 29 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

86

OVERALL SUMMARY

87

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

2016

23 22 18 38 36 18 26 9 35 38 9 21 4 25 28 17 23 10 35 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 † Clinical pregnancy: clinical intrauterine, heterotopic, or ectopic pregnancy

88

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

2016

41 52 53 38 37 33 43 24 36 38 19 31 20 25 28 33 50 31 36 36 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

89

Implantation rate

2016

26 44 30 32 32 25 40 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

90

Implantation rate by age at time of oocyte retrieval and type

• f treatment cycle

2016

35 47 53 36 33 26 32 24 32 33 13 30 17 19 26 26 44 30 32 32 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

91

Singleton ongoing clinical pregnancy by age at time of

• ocyte retrieval and type of treatment cycle

2016

19 19 13 32 31 14 18 9 29 28 6 11 19 22 14 19 9 29 30 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

S * Own oocytes exclusively † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound S Numbers less than 6 were suppressed

92

Singleton ongoing clinical pregnancy by age at time of

• ocyte retrieval and type of treatment cycle

2016

35 44 40 32 31 26 30 24 29 29 12 15 20 22 27 41 28 30 30 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

S * Own oocytes exclusively † Singleton pregnancy: ongoing clinical pregnancy with only one fetal heart beat on ultrasound S Numbers less than 6 were suppressed

93

CYCLES USING PGS

94

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 thaw

86.5% 92.9%

Number of clinical pregnancies

31,567 1,194

Proportion of clinical pregnancies per cycle start

28.6% 20.2%

Proportion of clinical pregnancies per ET cycle

37.5% 44.3%

95

PRIMARY TRANSFER RATE

96

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

97

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

98

Primary transfer clinical pregnancy rate, per patient

IVF and FET, 2013, 2014, 2015 and 2016

45.2 34.7 40.1 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 11,163 8,192 19,355

99

Primary transfer clinical pregnancy rate, per patient by

• ocyte type per patient

IVF and FET, 2013, 2014, 2015 and 2016

39.7 45.8 40.1 20 40 60 80 100 Own Donor OVERALL Percent per primary transfer (%)

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

Clinical pregnancy 17,889 1,466 19,355

100

Primary transfer clinical pregnancy rate, per patient with and without PGS

IVF and FET, 2013, 2014, 2015 and 2016

39.9 46.3 40.1 20 40 60 80 100 Excluding cycles with PGS Cycles with PGS OVERALL Percent per primary transfer (%)

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

Clinical pregnancy 18,697 658 19,355

101

Primary transfer clinical pregnancy rate, per batch of

• ocytes retrieved

IVF and FET, 2013, 2014, 2015 and 2016

46.9 34.0 39.5 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 9,773 9,608 19,381

102

Primary transfer clinical pregnancy rate, per batch of

• ocytes retrieved with and without PGS

IVF and FET, 2013, 2014, 2015 and 2016

39.2 46.7 39.5 20 40 60 80 100 Excluding cycles with PGS Cycles with PGS OVERALL Percent per primary transfer (%)

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

Clinical pregnancy 18,578 803 19,381

103

CUMULATIVE PREGNANCY RATE

104

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

105

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

106

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

107

Cumulative pregnancy rate, per patient

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

26.5 49.3 63.3 72.4 26.5 41.5 47.2 49.4 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.

108

Cumulative pregnancy rate, per batch of oocytes retrieved

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

25.6 54.8 70.4 78.9 25.6 36.4 38.7 39.1 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.

109

Optimistic cumulative pregnancy rate, per batch of oocytes retrieved

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

31.4 61.0 75.8 83.1 21.6 49.4 64.7 74.2 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.

110

Conservative cumulative pregnancy rate, per batch of oocytes retrieved

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

31.4 45.9 49.3 49.9 21.6 29.9 31.4 31.7 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 Conservative: Assumes that women who did not return for subsequent treatment cycles did not have a clinical pregnancy. .

111

Cumulative pregnancy rate, per batch of oocytes retrieved

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

31.4 61.0 75.8 83.1 21.6 49.4 64.7 74.2

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

Optimistic cumulative pregnancy rate

31.4 45.9 49.3 49.9 21.6 29.9 31.4 31.7

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.

112

Cumulative pregnancy rate, per batch of oocytes retrieved

PGS/PGD – IVF and FET – using own oocytes, 2013, 2014, 2015 and 2016

3.0 48.9 71.4 82.7 3.0 24.8 28.9 29.6 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.

113

Cumulative pregnancy rate, per batch of oocytes retrieved

PGS/PGD – IVF and FET – using own oocytes with an embryo transfer, 2013, 2014, 2015 and 2016

5.7 51.0 73.0 83.9 5.7 46.9 54.6 55.9 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.

114

PREGNANCY AND BIRTH OUTCOMES

ART vs. Non-ART − Ontario

115

Birth outcomes

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

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

• Adj. RR

(95%CI) n % n % Live birth

418,644 6,816 98.9 411,828 99.5 0.99 (0.99-1.00) 0.99 (0.99-1.00)

Stillbirth

2,055 54 0.78 2,001 0.48 1.62 (1.24-2.12) 1.56 (1.18-2.04)

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

116

Preterm birth

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

• Preterm birth:

– <37 weeks gestation – RR = 2.31 95% CI: 2.19−2.44 – adjusted RR = 2.20 95% CI: 2.09−2.33

• Singleton preterm births:

– <37 weeks gestation – RR = 1.65 95% CI: 1.53−1.77 – adjusted RR = 1.58 95% CI: 1.46−1.70

* Adjusted for maternal age at delivery.

117

Gestational age at time of delivery

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

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

• Adj. RR

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

5,399 203 2.95 5,196 1.25 2.35 (2.04-2.70) 2.20 (1.91-2.54)

32 weeks

1,315 64 0.93 1,251 0.30 3.07 (2.39-3.95) 2.89 (2.24-3.73)

33 weeks

2,038 102 1.48 1,936 0.47 3.17 (2.60-3.86) 2.95 (2.41-3.61)

34 weeks

3,683 154 2.24 3,529 0.85 2.62 (2.24-3.08) 2.42 (2.06-2.85)

35 weeks

6,022 217 3.15 5,805 1.40 2.25 (1.97-2.57) 2.21 (1.93-2.54)

36 weeks

12,414 405 5.88 12,009 2.90 2.03 (1.84-2.23) 1.94 (1.76-2.13)

≥37 weeks

390,066 5744 83.38 384,322 92.82 0.90 (0.89-0.91) 0.90 (0.89-0.91)

* Adjusted for maternal age at delivery.

118

Gestational age at time of delivery for singleton pregnancies

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

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

• Adj. RR

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

4831 122 2.05 4709 1.15 1.77 (1.48-2.12) 1.67 (1.39-1.99)

32 weeks

1099 39 0.65 1060 0.26 2.52 (1.83-3.46) 2.33 (1.68-3.22)

33 weeks

1708 47 0.79 1661 0.41 1.94 (1.45-2.58) 1.78 (1.33-2.38)

34 weeks

3166 78 1.31 3088 0.76 1.73 (1.38-2.16) 1.61 (1.28-2.02)

35 weeks

5269 113 1.90 5156 1.26 1.50 (1.25-1.80) 1.50 (1.24-1.80)

36 weeks

10994 237 3.97 10757 2.64 1.51 (1.33-1.71) 1.46 (1.29-1.66)

≥37 weeks

386984 5327 89.33 381657 93.52 0.96 (0.95-0.96) 0.96 (0.95-0.97)

* Adjusted for maternal age at delivery.

119

CLOSING REMARKS

120

Key messages

• Decreased multiple pregnancy rate
• Increased proportion:

– freeze all cycles – PGS/PGD – FET cycles

• 40% clinical pregnancy rate for primary transfers

121

THANK YOU!

• Dr. Andrea Lanes, Epidemiologist

alanes@bornontario.ca Moya Johnson, Coordinator – CARTR Plus mojohnson@bornontario.ca Shelley Dougan, Clinical Program Development Lead sdougan@bornontario.ca

• Dr. Hao Wang, Research Statistician

haowang@bornontario.ca Acknowledgment Noa Capelle