Assisted reproductive technologies (ART) in Canada: 2001 results from the Canadian ART Register

Article Outline

• Abstract
• Materials and methods
  • Definitions of Outcomes
• Results
  • Participating Centers
  • Success Rates by Type of ART Procedure
  • In Vitro Fertilization/Intracytoplasmic Sperm Injection
  • Gamete Intrafallopian Transfer
  • IVF/ICSI with Donor Oocytes
  • Frozen Embryo Transfer
  • FET with Donor Oocytes or Donor Embryos
  • Gestational Carrier Cycles
  • Other Cycle Types
  • Birth Outcomes
  • Effect of Female Age
  • Effect of Infertility Diagnosis
  • Effect of Number of Embryos Transferred
  • Effect of Day of ET
  • Effect of Surplus Embryos for Cryopreservation
  • Complications and Pregnancy Reduction
• Discussion
• Acknowledgments
• APPENDIX. 
  • Canadian ART Centers Reporting Data to CARTR for 2001
• References
• Copyright

Objective

To present the success rates of assisted reproductive technologies (ART) cycles performed in 2001 in Canada.

Design

Retrospective cohort study.

Setting

Nineteen of 22 ART centers in Canada.

Participants

Couples undergoing ART treatment in Canada during 2001.

Methods

Data on each ART cycle performed during 2001 were submitted electronically to the Canadian ART Register (CARTR) by participating centers.

Main Outcome Measure(s)

Clinical pregnancy and live birth rate per cycle started, multiple birth rate.

Result(s)

A total of 7,884 ART cycles was reported to CARTR. There were 5,393 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles using the woman’s own oocytes. Per cycle started, the pregnancy rate was 28.3%, and the live birth rate was 23.1%; the multiple birth rate per delivery was 32.8%. Of cycles with oocytes retrieved, IVF was performed in 44% and ICSI in 56%; the outcomes were similar with the two procedures. There were 301 IVF/ICSI cycles using donor oocytes. The pregnancy rate was 29.2%, and the live birth rate was 22.4%; the multiple birth rate was 43.5%. There were 1,936 frozen embryo transfer cycles using the woman’s own oocytes. The pregnancy rate was 18.9%, and the live birth rate was 15.4%; the multiple birth rate was 24.9%.

Conclusion(s)

For 2001, CARTR achieved 86% voluntary participation from Canadian ART centers. Pregnancy and live birth rates comparable to those of other countries were achieved.

Key Words:  ART , success rates , IVF , ICSI , frozen embryo transfer , oocyte donation , multiple births

The Canadian Assisted Reproductive Technologies Register (CARTR) was first established in 1999 for the collection of treatment cycle data from Canadian fertility centers using assisted reproductive technologies (ART), including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), gamete intrafallopian transfer (GIFT), and frozen embryo transfer (FET). The establishment of the register was initiated by the IVF Directors Group of the Canadian Fertility and Andrology Society (CFAS) and implemented by the Data Subcommittee of the CFAS Accreditation Committee. Participation of ART centers in CARTR is voluntary.

The reasons for the establishment of CARTR were [1] to collect and maintain a database of results of all ART cycles initiated in Canadian centers, [2] to calculate overall success rates in terms of clinical pregnancy and live birth per cycle started for the variety of different types of ART procedures being offered, [3] to provide estimates for the likelihood of undesired events from ART treatment, such as miscarriage, ectopic pregnancy, ovarian hyperstimulation syndrome, and multiple birth, [4] to identify predictors of outcome, so that treatment options can be provided more efficiently, [5] to obtain baseline event rates to assist in developing proposals for intervention studies, [6] to evaluate the provision of services from a quality assurance perspective, [7] to provide realistic expectations and options for infertile couples wishing to avail themselves of treatment with ART, and [8] to provide guidelines for resource allocation.

The purpose of this article is to report the results of ART cycles performed in Canadian centers in the 2001 calendar year and submitted to CARTR.

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Materials and methods 

The Society for Assisted Reproduction (SART) in the United States generously provided CFAS with permission to use their computerized Clinical Outcome Reporting System (CORS). Since the 1999 reporting year, CARTR has been using SART-CORS version 2. This computer program was provided to all Canadian ART centers at no charge. Staff at each center entered information about patient demographics, diagnosis, and obstetrical history, details of treatment, and pregnancy and birth outcomes for each ART treatment cycle initiated. The completed anonymous case records were sent electronically from each center to the CARTR coordinating center, where they were checked for accuracy and completeness, with corrections or clarifications requested from the centers as necessary. The records from each clinic were then aggregated for data analysis with the software program Statistical Package for the Social Sciences, version 10 (SPSS, Chicago, IL). For this report, ART cycles started between January 1, 2001 and December 31, 2001 were submitted.

It was not necessary to obtain institutional review board approval for this study because the data collection is one of the requirements for accreditation of clinics providing ART services, which is organized by the CFAS in conjunction with the Canadian Council on Health Services Accreditation. Although participation in accreditation is voluntary, most of the clinics in Canada have agreed to the process and are obliged to inform patients that such data will be collected in a manner that is anonymous.

When CARTR was established, one of the conditions under which the directors of the various Canadian centers agreed to provide data was complete confidentiality of the information. In keeping with this agreement, the results of the yearly analysis of aggregated data from CARTR have been provided, to this point, only to the medical and laboratory directors of the ART centers that submitted data for that year. This has been done through a slide presentation at the annual IVF Directors’ Meeting. Identified clinic-specific results have never been presented, at the directors’ request, and are not available to anyone at this time. A brief summary of the national pregnancy and live birth rates has been provided to the media, with the directors’ permission, immediately after each meeting. At the 2003 IVF Directors’ Meeting, the participants agreed to the publication, in a major medical journal, of a complete report of the CARTR results from 2001. Before submission for publication, this report was read and approved by all IVF directors.

Definitions of Outcomes 

A cycle is considered to have “started” when a woman undergoing ovarian stimulation receives the first dose of gonadotropins or, in a nonstimulated cycle (e.g., for FET), when a decision is made to attempt ART treatment in that cycle. A canceled cycle is one that is stopped before the oocyte retrieval procedure or thawing of embryos.

Clinical pregnancy includes intrauterine gestation (presence of a fetal sac on ultrasonography), ectopic pregnancy, and miscarriage occurring before an ultrasound examination has been done with histological evidence of pregnancy. Cycles with only a positive pregnancy test are not considered to be clinical pregnancies.

Pregnancy loss includes miscarriage and therapeutic abortion occurring at ≤20 weeks’ gestation. Any pregnancy termination, either spontaneous or therapeutic, occurring after 20 weeks’ gestation with no liveborn infant is considered a stillbirth. A delivery is the birth of one or more infants, either living or not, after 20 weeks’ gestation. A live birth is a delivery that results in at least one living infant (but, if a multiple birth, might include one or more stillborn infants). A neonatal death is the death of an infant in the first 28 days of life. A multiple birth is the delivery of more than one infant, either liveborn or stillborn, including deliveries with all infants stillborn. High-order multiple births (triplets and quadruplets) are reported separately.

Unless otherwise noted, the clinical pregnancy rate is reported per cycle started. Cycle cancellation, ectopic pregnancy, and other complications are reported per cycle started. The miscarriage rate is reported per intrauterine pregnancy. The live birth rate is reported per cycle started, excluding from the denominator cycles in which the outcome of the pregnancy has not been reported (outcomes were unknown for only 3% of ongoing pregnancies). Because of these missing data, the live birth rates reported might underestimate the true live birth rates. The multiple birth rate is reported per delivery, including stillbirths.

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Results 

Participating Centers 

Although ART centers are located in every Canadian province except Newfoundland and Prince Edward Island, approximately half the centers are located in Ontario, mainly in the Toronto area. Of the 22 ART centers operating in 2001, 19 contributed to CARTR for that year (listed in the Appendix). Three centers, all in the province of Quebec, declined to participate.

Of the 19 centers, 5 performed >500 ART cycles in 2001, 10 performed 200–500 cycles, and 4 performed <200 cycles.

Success Rates by Type of ART Procedure 

In total, 7,884 treatment cycles involving ART were reported to CARTR in 2001. Overall, 1,983 ART cycles (25.9% of cycles started) resulted in a clinical pregnancy, 1,668 resulted in a delivery (21.5%), and 1,645 resulted in a live birth (21.2%) (there were 51 cycles with ongoing pregnancies for which the birth outcome was not reported). Overall, there were 527 multiple births (31.6% of known births): 479 twin births (28.7%), 44 triplet births (2.6%), and 4 quadruplet births (0.2%).

The various procedures and their success rates are described below. The results of the most common procedures are summarized in Table 1.

TABLE 1. Cycle outcomes for the most common types of ART procedures.

Outcome	IVF/ICSI	IVF/ICSI-DO	FET	FET-DO
Cycles started	5,393	301	1,936	152
Canceled cycles (% of cycles started)	599(11.1)	24(8.0)	84(4.3)	3(2.0)
Oocyte retrievals (% of cycles started)	4,794(88.9)	277(92.0)	—	—
Embryo transfers (% of cycles started)	4,494(83.3)	263(87.4)	1,779(91.9)	147(96.7)
Clinical pregnancy (% per cycle started)	1,528(28.3)	88(29.2)	365(18.9)	26(17.1)
Ectopic pregnancy (% per cycle started)	38(0.7)	3(1.0)	7(0.4)	0
Pregnancy loss (% per IU pregnancy)	193(13.0)	14(16.5)	52(14.5)	7(26.9)
Deliverya (% per cycle started)	1,257(23.5)	69(23.1)	297(15.4)	19(12.5)
Live birtha (% per cycle started)	1,237(23.1)	67(22.4)	296(15.4)	19(12.5)
Singleton live birtha (% per cycle started)	830(15.5)	38(12.7)	222(11.5)	14(9.2)
Singleton deliverya (% of deliveries)	845(67.2)	39(56.5)	223(75.1)	14(73.7)
Twin deliverya (% of deliveries)	378(30.1)	25(36.2)	65(21.9)	5(26.3)
Triplet or quadruplet deliverya (% of deliveries)	34(2.7)	5(7.2)	9(3.0)	0

Note: DO = donor oocyte.

Gunby. Canadian ART Register 2001. Fertil Steril 2005.

In Vitro Fertilization/Intracytoplasmic Sperm Injection 

In vitro fertilization, including ICSI, was the most common procedure performed, with 5,393 cycles reported. This category includes only cycles in which the woman’s own oocytes are used and the same woman receives the resulting embryos, to distinguish them from donor oocyte and gestational carrier cycles (see below). However, cycles using donated sperm are included. Because the decision to use ICSI might not be made until the sperm and oocytes are assessed in the embryology laboratory, cycles canceled before oocyte retrieval cannot be classified by type of insemination procedure; thus, results per cycle started can only be calculated for IVF and ICSI cycles grouped together.

Per cycle started, the pregnancy rate was 28.3%, the live birth rate was 23.1%, and the singleton live birth rate was 15.5%. There were 38 ectopic pregnancies (0.7%), including 2 heterotopic pregnancies with nonviable intrauterine gestations. The pregnancy loss rate was 13.0%, including 5 therapeutic abortions. Of the 1,257 known births (97% of ongoing pregnancies), 32.8% were multiple births (30.1% twins, 2.5% triplets, and 0.2% quadruplets). Included in these figures are 6 pregnancies and 5 live births (3 singleton, 1 twin, and 1 triplet) that resulted from intrauterine insemination (IUI) performed after the IVF/ICSI cycle was canceled.

Rates for IVF and ICSI separately can only be provided per successful retrieval (i.e., one or more oocytes retrieved). Of 4,767 IVF/ICSI cycles with a successful retrieval, 44.2% had insemination by standard IVF, and 55.8% had ICSI. The pregnancy rate per successful retrieval was 30.9% for IVF and 32.8% for ICSI, and the live birth rates were 25.0% and 27.0%, respectively. The ectopic pregnancy rate was 0.7% with IVF and 0.8% with ICSI, and the pregnancy loss rates were 14.0% and 12.2%, respectively. Of 537 known births after IVF, 33.3% were multiple births (29.2% twins, 3.7% triplets, and 0.4% quadruplets). Of 715 known births after ICSI, 32.3% were multiple births (30.8% twins, 1.4% triplets, and 0.1% quadruplets).

Gamete Intrafallopian Transfer 

Gamete intrafallopian transfer, in which the oocytes and sperm are transferred separately to the fallopian tube, so that fertilization occurs in vivo, is a procedure rarely used in Canada in recent years; in fact, only eight cycles with GIFT were reported to CARTR for 2001.

In these cycles, the pregnancy rate was 37.5%, the live birth rate was also 37.5%, and the singleton live birth rate was 25.0%. One of the three births (33.3%) was multiple (twins).

IVF/ICSI with Donor Oocytes 

In vitro fertilization/intracytoplasmic sperm injection carried out with donor oocytes (IVF/ICSI-DO) was reported in 301 cycles in 2001. In IVF/ICSI-DO, one woman undergoes ovarian stimulation, then donates some or all of the retrieved oocytes to another woman, usually anonymously. These oocytes are inseminated with sperm from the recipient’s partner (or a sperm donor), and the resulting embryos are transferred to the uterus of the recipient.

In donor oocyte cycles, the pregnancy rate was 29.2%, the live birth rate was 22.4%, and the singleton live birth rate was 12.7%. There were three ectopic pregnancies (1.0%). The miscarriage rate was 16.5%. Of 69 known births (97% of ongoing pregnancies), 43.5% were multiple births (36.2% twins, 5.8% triplets, and 1.4% quadruplets).

Of 277 donor oocyte cycles with a successful retrieval, 37.9% had insemination by standard IVF, and 62.1% had ICSI. The pregnancy rate per successful retrieval was 31.4% for IVF and 32.0% for ICSI.

Frozen Embryo Transfer 

Frozen embryo transfer involves thawing embryos created and cryopreserved in a previous IVF/ICSI cycle and transferring them to the uterus of the woman who provided the oocytes in the original cycle. In 2001, 1,936 such cycles were reported.

The pregnancy rate was 18.9%, the live birth rate was 15.4%, and the singleton live birth rate was 11.5%. There were seven ectopic pregnancies (0.4%). The miscarriage rate was 14.5%. Of 297 known births (97% of ongoing pregnancies), 24.9% were multiple births (21.9% twins and 3.0% triplets).

FET with Donor Oocytes or Donor Embryos 

The category FET-DO includes transfer of cryopreserved embryos created from donor oocytes in a previous IVF/ICSI-DO cycle (123 cycles) and cryopreserved donated embryos (29 cycles). In the latter case, both the male and female gametes were provided by a couple other than the intended parenting couple. The thawed embryos are transferred to the woman who intends to raise the child.

In this category, the pregnancy rate was 17.1%, the live birth rate was 12.5%, and the singleton live birth rate was 9.2%. There was no ectopic pregnancy. The miscarriage rate was 26.9%. All 19 ongoing pregnancies had births reported, with a multiple birth rate of 26.3% (all twins).

Gestational Carrier Cycles 

There were 78 cycles in which embryos were transferred into the uterus of a woman other than the one who intended to raise the child. Gestational carriers were used in 30 IVF/ICSI and 21 FET cycles with the parenting woman’s own oocytes and 18 IVF/ICSI and 9 FET cycles with donor oocytes. Donor sperm was used in 2 cycles.

In fresh embryo cycles using a gestational carrier, the pregnancy rate was 37.5%, the live birth rate was 33.3%, and the singleton live birth rate was 27.1%; in frozen embryo cycles, the rates were 16.7%, 6.7%, and 6.7%, respectively. Of the 23 pregnancies in gestational carriers, 1 was ectopic (1.3%), and 4 ended in miscarriage (18.2%). All 18 ongoing pregnancies had births reported, with a multiple birth rate of 16.7% (all twins).

Other Cycle Types 

There were a few other ART procedures performed in 2001 that did not fit into the categories described above. These included IVF/ICSI cycles involving in vitro oocyte maturation (2 cycles), preimplantation genetic diagnosis (3 cycles), or embryo banking (all embryos cryopreserved, no embryo transfer (ET) intended, 1 cycle), and 10 cycles of controlled ovarian stimulation for the purpose of IUI that were converted to IVF/ICSI cycles when hyperstimulation occurred.

Birth Outcomes 

A total of 2,247 infants was born from all types of ART cycles started in 2001 in Canada: 1,141 singletons (50.8% of infants), 958 twins (42.6%), 132 triplets (5.9%), and 16 quadruplets (0.7%). An additional 51 pregnancies had no delivery information reported.

Of the 1,141 infants born as singletons, there were 17 stillbirths and 9 neonatal deaths, for a total perinatal mortality rate of 2.3%. The take-home baby rate was 98%. The median gestational age at birth was 39 weeks (range, 20–43 weeks). Preterm delivery (<37 weeks) occurred in 15.7% of births and very preterm delivery (<34 weeks) in 5.4% of births. The birth weight was >2,500 g for 89.6% of singletons, 2,000–2,500 g for 7.1%, 1,000–1,999 g for 2.3%, and <1,000 g for 1.0%. Some type of birth defect was reported for 26 infants (2.3%).

Of the 958 infants born as twins, there were 15 stillbirths and 20 neonatal deaths, for a total perinatal mortality rate of 3.7%. The take-home baby rate was 98%. The median gestational age at birth was 36 weeks (range, 20–43 weeks). Preterm delivery occurred in 65.5% of births and very preterm delivery in 28.6% of births. Birth weight was >2,500 g for 47.3% of twins, 2,000–2,500 g for 26.6%, 1,000–1,999 g for 22.6%, and <1,000 g for 3.5%. Some type of birth defect was reported for 17 infants (1.8%).

Of the 132 infants born as triplets, there was 1 stillbirth and 8 neonatal deaths, for a total perinatal mortality rate of 6.8%. The take-home baby rate was 98%. The median gestational age at birth was 33 weeks (range, 23–39 weeks). Preterm delivery occurred in 97.6% of births and very preterm delivery in 66.7% of births. Birth weight was >2,500 g for 5.7% of triplets, 2,000–2,500 g for 24.6%, 1,000–1,999 g for 53.3%, and <1,000 g for 16.4%. Two infants were reported to have some type of birth defect (1.5%).

Of the 16 infants born as quadruplets, there were no stillbirths and 3 neonatal deaths (all in the same set), for a total perinatal mortality rate of 18.8%. The take-home baby rate was 100%. The median gestational age at birth was 32 weeks (range 25–34 weeks). All 4 deliveries were very preterm. Birth weight was 2,000–2,500 g for 25% of quadruplets and 1,000–1,999 g for 75%. No birth defect was reported.

The information provided on birth defects was limited. Overall, some type of birth defect was reported for 45 infants (2.0%): 1 case of cleft palate, 6 cases of genetic defect (1 neonatal death), 10 cases of cardiac defect (1 neonatal death), 6 cases of limb defect, and 22 cases of other unspecified defects (3 stillbirths and 5 neonatal deaths).

Effect of Female Age 

The pregnancy and birth results for women categorized into three age groups are given in Table 2. The mean female age was 35 years in IVF/ICSI cycles and FET cycles and 40 years in donor oocyte cycles. The proportion of cycles in women aged ≥40 years was 16% in IVF/ICSI cycles, 13% in FET cycles, and 54% in donor oocyte cycles. In IVF/ICSI and FET cycles, the pregnancy and birth rates declined with female age, especially after age 40 years. In donor oocyte cycles, pregnancy and live birth rates were similar in all age groups.

TABLE 2. Pregnancy and birth results by female age for the most common ART procedures.

Outcome/female age group	IVF/ICSI	IVF/ICSI-DO	FET
Mean female age (range) (y)	35(21–49)	40(23–54)	35(19–48)
Cycles started (% of cycles within procedure)
<35 y	2,394(44.4)	59(19.7)	868(44.9)
35–39 y	2,148(39.8)	79(26.3)	819(42.3)
≥40 y	851(15.8)	162(54.0)	247(12.8)
Clinical pregnancy (% per cycle started)
<35 y	833(34.8)	14(23.7)	182(21.0)
35–39 y	585(27.2)	24(30.4)	159(19.4)
≥40 y	110(12.9)	50(30.9)	23(9.3)
Live birtha (% per cycle started)
<35 y	715(30.1)	9(15.5)	148(17.1)
35–39 y	455(21.4)	17(21.5)	132(16.2)
≥40 y	67(7.9)	41(25.3)	16(6.5)
Multiple birtha (% per delivery)
<35 y	264(36.5)	2(22.2)	37(25.0)
35–39 y	132(28.3)	7(36.8)	36(27.3)
≥40 y	16(23.5)	21(51.2)	1(5.9)

Gunby. Canadian ART Register 2001. Fertil Steril 2005.

There are several steps at which female age has an effect on the success of the treatment cycle. The proportions of cycles that were canceled or had a failed retrieval attempt increased with increasing female age, whereas, correspondingly, the proportion of cycles with successful retrieval (at least one oocyte retrieved) decreased (92% for women aged <35 years, 87% for those aged 35–39 years, and 82% for those aged ≥40 years). The mean number of oocytes retrieved decreased with age, especially after age 40 years (13.0, 11.4, and 8.5, respectively). Once oocytes were retrieved, the proportion of cycles progressing to ET was similar in the three age groups (91%–95%). In women who had one or more embryos replaced, the pregnancy rate progressively declined with increasing female age (39.8%, 33.1%, and 17.4%), even though older women had more embryos transferred (mean 2.4, 2.8, and 3.1). In women who became pregnant, the pregnancy loss rate became higher as women aged (8.9%, 15.1%, and 33.0%). The proportion of women who had surplus embryos available for cryopreservation gradually decreased from the younger to older women (52.3%, 39.3%, and 21.0%), and this trend was also apparent in the average number of embryos frozen per cycle (2.9, 2.0, and 1.0).

Effect of Infertility Diagnosis 

The distribution of primary diagnostic categories was quite different in IVF and ICSI cycles (Table 3). The most common diagnosis for couples having IVF was tubal factor (50%), followed by idiopathic or unexplained infertility (23%). The most common diagnosis for couples having ICSI was male factor (56%), followed by tubal factor (16%) and idiopathic infertility (13%). In IVF cycles, couples with a primary diagnosis of endometriosis or ovulatory disorder had the highest pregnancy rates (40% and 37% per successful retrieval, respectively), whereas those with a diagnosis of male or tubal factor had the lowest rates (27% and 28%, respectively). In ICSI cycles, couples with a primary diagnosis of male factor had the highest pregnancy rate (37%), whereas those with a diagnosis of endometriosis had the lowest rate (22%).

TABLE 3. Pregnancy rates per successful retrieval for IVF and ICSI cycles by diagnostic category.

Primary diagnosis	Canceleda (no. of cycles)	IVF		ICSI
		No. of cycles (% of all IVF cycles)	No. of pregnancies (% per retrieval)	No. of cycles (% of all ICSI cycles)	No. of pregnancies (% per retrieval)
Male factor	191	98(4.6)	26(26.5)	1,489(56.0)	543(36.5)
Tubal factor	167	1,057(50.1)	300(28.4)	359(13.5)	98(27.3)
Idiopathic	115	477(22.6)	153(32.1)	349(13.1)	114(32.7)
Endometriosis	64	204(9.7)	81(39.7)	177(6.7)	39(22.0)
Ovulatory disorder	32	124(5.9)	46(37.1)	145(5.5)	44(30.3)
Other	44	148(7.0)	45(30.4)	140(5.3)	33(23.6)

Gunby. Canadian ART Register 2001. Fertil Steril 2005.

Effect of Number of Embryos Transferred 

The number of embryos transferred in IVF/ICSI cycles ranged from 1 to 8, with a mean of 2.6. In the majority of cycles, either 2 (43%) or 3 (35%) embryos were transferred. The number of embryos transferred varied greatly by female age, with more embryos being transferred in the older women in an attempt to compensate for declining fertility: mean 2.4 embryos in the <35 years group, 2.8 in the 35–39 years group, and 3.1 in the ≥40 years group.

The pregnancy rates per ET procedure were low when only one embryo was transferred (14.5%) (Table 4). Transferring more than two embryos did not increase the pregnancy rate beyond the high level observed with two embryos (38.3%); indeed, the pregnancy rate declined with increasing numbers of embryos transferred, reflecting the influence of female age and embryo quality. Twenty-five percent of two-embryo transfers were performed on day 5 after oocyte retrieval, with 71% performed on day 3. However, the pregnancy rates were similar at 39.5% and 38.2%, respectively. In contrast, only 4% of three-embryo transfers and 2% of four-embryo transfers were performed on day 5.

TABLE 4. Pregnancy rate per ET procedure and multiple birth rate per known birth by number of embryos transferred in IVF/ICSI cycles.

No. of embryos transferred	Pregnancy		Multiple birth
	No. of cycles (% of all ET cycles)	No. of pregnancies (% per ET)	No. of births (% of all births)	No. of multiple births (% per birth)	No. of triplet or quad births (% per birth)
1	289(6.4)	42(14.5)	32(2.6)	1(3.1)	0
2	1,930(43.0)	740(38.3)	648(51.8)	213(32.9)	5(0.8)
3	1,549(34.5)	535(34.5)	432(34.5)	153(35.4)	24(5.6)
4	618(13.8)	172(27.8)	115(9.2)	37(32.2)	2(1.7)
5 or more	102(2.3)	32(31.4)	24(1.9)	5(20.8)	2(8.3)

Gunby. Canadian ART Register 2001. Fertil Steril 2005.

Except for cycles in which only one embryo was transferred (there was one twin pregnancy in this group), the multiple birth rate was fairly similar, regardless of the number of embryos transferred: 32.9%, 35.4%, and 32.2% for two, three, and four embryos, respectively. The multiple birth rate was somewhat lower, at 20.8%, in cycles with five or more embryos transferred, but this might reflect, again, higher female age, poor embryo quality, or the small number of cycles in this group. The triplet/quadruplet rate was 0.8% when two embryos were transferred, compared with 4.9% when three or more embryos were transferred. Interestingly, three of the four quadruplet births all resulted from cycles with three embryos transferred.

Effect of Day of ET 

In IVF/ICSI cycles, ET was performed on day 2 (after oocyte retrieval) in 3% of transfers, day 3 in 82%, and day 5 in 14%. The proportions varied greatly among clinics. All but one clinic performed the majority of their ETs on day 3, with only four clinics performing >5% of transfers on day 2 and five clinics performing >5% of transfers on day 5. Women having ET on day 2 or 3 were less likely than those having ET on day 5 to have had a previous ART attempt (27% and 31% vs. 47%). Women with ET on day 2 were slightly older than those with transfer on days 3 or 5 (mean age 35.5 years vs. 34.9 years and 34.2 years) and had fewer oocytes retrieved (mean 8.4 vs. 11.9 and 12.6). More embryos were transferred to each woman on day 2 and 3 than on day 5 (mean 2.7 and 2.7 vs. 2.1). The proportion of cycles with two embryos transferred was 28% on day 2, 37% on day 3, and 80% on day 5.

The pregnancy rates per ET procedure were 26.0% on day 2, 33.8% on day 3, and 36.3% on day 5. The multiple birth rates were 24.0%, 32.8%, and 32.6%, respectively.

Effect of Surplus Embryos for Cryopreservation 

The availability of surplus embryos for cryopreservation might be an indicator of embryo quality, as well as embryo number. Women who have many embryos available will have the best quality ones selected for fresh ET, whereas in women with only one or two embryos available, embryo quality might not be as high. Thus, it is interesting to compare pregnancy rates within a given number of embryos transferred, for cycles with and without embryos available for cryopreservation (Table 5).

TABLE 5. Pregnancy rate per ET procedure by number of embryos transferred and whether surplus embryos were available for cryopreservation.

Gunby. Canadian ART Register 2001. Fertil Steril 2005.

In Canada in 2001, a single embryo was transferred by choice in only 31 cycles (11% of single embryo cycles and 0.7% of all transfer cycles). The pregnancy rate per ET was 35.5% in elective single-embryo transfers but only 12.0% in non-elective single-embryo transfers.

About half of two- and three-embryo transfers had surplus embryos; in these cycles, the pregnancy rates were significantly higher than when no surplus embryo was available: 48.4% vs. 25.2% for two-embryo transfers and 44.1% vs. 27.7% for three-embryo transfers.

Complications and Pregnancy Reduction 

Complications were reported in 141 IVF/ICSI cycles (2.7%). There were 113 cases of ovarian hyperstimulation syndrome (2.1% per cycle started), 33 of which (29%) required hospitalization, 15 complications related to medications (1 hospitalization), and 13 complications related to procedures (9 hospitalizations).

Of 626 multiple pregnancies from all type of ART cycles, 13.3% had spontaneous pregnancy reduction (loss of one or more but not all fetuses), and 4.0% had therapeutic pregnancy reduction, following ultrasonographic confirmation of fetal viability at approximately 8 weeks’ gestation. Of 529 pregnancies that were originally twins, reduction to one fetus occurred spontaneously in 10.4% and therapeutically in 0.6%. Of 88 pregnancies that were originally triplets, reduction to two fetuses occurred spontaneously in 21.6% and therapeutically in 19.3% and reduction to one fetus in 8.0% and 2.3%, respectively. Thus, fewer than half of the viable triplet pregnancies resulted in a triplet birth. Of 9 pregnancies that were originally quadruplets, reduction to three fetuses occurred spontaneously in 22.2% and to two fetuses occurred therapeutically in 33.3%. Fewer than half of the viable quadruplet pregnancies resulted in a quadruplet birth, but two thirds resulted in a high-order multiple birth (four quadruplets and two triplets).

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Discussion 

In this first annual report from the Canadian ART Register, we have presented the results of ART cycles performed in Canada in 2001. The data are as complete and accurate as possible, but there are at least three areas in which the data collection could be improved.

First, because participation is voluntary, not all Canadian ART centers submitted data to CARTR. For 2001, three centers declined to submit data, although subsequently two of these have begun to participate in the Register. It is estimated that perhaps 1,500 Canadian ART cycles were omitted from the Register in 2001 because of the nonparticipation of these three centers. The established Canadian ART centers are committed to submitting data to CARTR on a yearly basis, and as new centers are set up, they too are keen to participate. It is hoped that, in the near future, we will have 100% voluntary participation in CARTR.

At present, CARTR is not regulated by the government of Canada and receives no government funding. It is responsible only to the IVF Directors Group of the CFAS and is operated solely on funds generated from a per-cycle fee charged to the participating centers. This situation is likely to change, however, because recently passed federal legislation has called for a mandatory ART register in Canada.

A second source of incomplete data is the 3% of ongoing pregnancy cycles that are missing follow-up to birth. Centers for ART generally refer a successful patient back to her own physician as soon as a viable pregnancy is confirmed (at approximately 8 weeks’ gestation). It takes some effort on the part of clinic personnel to track down the birth outcomes, especially for women from out of town. Although clinical pregnancy is the most immediate relevant outcome of an ART cycle, a live birth is obviously the most important result for the couple undergoing treatment. Because it would be incorrect to assume that all pregnancies with unknown birth outcome resulted in a live birth, yet overly pessimistic to categorize them all as pregnancy losses, we have chosen to leave these outcome-unknown cycles out of the denominator when calculating live birth rates. This method results in an underestimate of the true live birth rate.

A third aspect that might affect the accuracy and completeness of the data reported here is one that is presently not quantifiable. That aspect is the accuracy of the data provided to the Register by each center. Although the data are checked manually on receipt by the CARTR coordinator for obvious errors, omissions, and inconsistencies, there is no guarantee, beyond the best efforts of the person responsible for data entry at each center, that the data submitted are accurate, that all cycles are included, and that all pregnancies and their outcomes are properly recorded. In the SART program in the United States, random checks of the submitted information against source documents are carried out on a revolving basis to verify the accuracy of the data; however, such a practice is not feasible at this time in Canada. The reliability of the CARTR report rests on the trust that personnel from each center have submitted accurate and complete data to the best of their ability.

In this report, we have presented aggregate data for all ART centers combined. In some other national ART registers, notably SART in the United States and the Human Fertilisation and Embryology Authority (HFEA) in the United Kingdom, the success rates of each center are presented separately, so that the consumer might easily make comparisons among centers. However, the IVF Directors Group felt very strongly that the presentation of center-specific data should not be a mandate of CARTR. Even within the group, the success rates of individual centers are not shared, although many centers choose to provide information to the public on their web sites. One of the reasons for withholding center-specific data is that comparisons across centers might not be valid, even if results are presented stratified by female age.

There are many reasons, other than the skills of the physicians, nurses, and embryologists, why one center could have a higher or lower success rate than another center. First is the type of patient treated. Female age is one of the strongest prognostic factors predicting success in ART treatment. Although the results might be stratified by female age, within, say, the 35–39-year age group, one center might treat a higher proportion of women aged 38 and 39 years than the next center. Other important prognostic factors include cause of infertility, duration of infertility, previous number of ART cycles and other fertility treatments, and a history of previous pregnancy or birth. These factors might vary substantially among the patient populations of each center.

In addition, there are aspects of the ART cycle itself that have a profound effect on the success of treatment, in particular, the aggressiveness of the ovarian hyperstimulation regimen and the number of embryos transferred. Undoubtedly, women with many oocytes retrieved and several embryos transferred have a higher than average chance of achieving a pregnancy, but there are also costs involved (i.e., increased risks of ovarian hyperstimulation syndrome and multiple pregnancy). The use of ICSI, rather than standard IVF, also varies among clinics. Although the CARTR data show slightly higher pregnancy rates for cycles using ICSI, this finding might be due to the different types of patients for whom each technique is used. Except for cases of severe male factor infertility, it is not certain whether ICSI is the best choice for a given couple. Nor has it yet been definitely demonstrated that ICSI is without risks to the resulting child.

It is interesting to compare the results reported here for CARTR with those for the same year from SART in the United States (1) and the European IVF-monitoring (EIM) program, involving 23 countries in Europe (2) (Table 6). However, one must keep in mind the differences among patient populations discussed above, which apply even more strongly when making comparisons across countries and continents. The most striking difference between CARTR and the other two reports is the much smaller numbers of ART clinics participating and ART cycles performed, corresponding to Canada’s small population. Of interest is that, for virtually every outcome, Canada’s results fall midway between those of the United States and Europe.

TABLE 6. Comparison of 2001 results for IVF/ICSI, FET, and IVF/ICSI-DO from CARTR, SART in the United States, and the EIM program in 23 European countries.

Outcome	CARTR	SART	EIM
No. of clinics participating (%)	19 (86)	384 (91)	579 (<68)
Total no. of cycles reported	7,884	107,587	289,690
IVF/ICSI cycles
No. of cycles reported	5,393	80,664	235,324
% of cycles with ICSI	56	50	49
% of cycles in women aged ≥40 y	16	19	Range 7–23
% of cycles with ≤2 embryos transferred	49	34	64
Clinical pregnancy rate per cycle (%)	28	33	23
Live birth rate per cycle (%)	23	27	17
Singleton live birth rate per cycle (%)	15	20	13
Multiple delivery rate per delivery (%)	33	36	25
Triplet or quadruplet delivery rate per delivery (%)	2.7	3.8	1.5
FET cycles
No. of cycles reported	1,936	14,075	41,583a
Clinical pregnancy rate per cycle (%)	19	27	16
Live birth rate per cycle (%)	15	22	12
Singleton live birth rate per cycle (%)	12	16	10
Multiple delivery rate per delivery (%)	25	24	16
Triplet or quadruplet delivery rate per delivery (%)	3.0	2.6	0.8
IVF/ICSI-DO cycles
No. of cycles reporteda	263	7,991b	7,171
Clinical pregnancy rate per ET (%)	33	—	33
Live birth rate per ET (%)	26	47	—

Note: SART data from The Centers for Disease Control and Prevention et al. (1); EIM data from Nyboe Andersen et al. (2).

Gunby. Canadian ART Register 2001. Fertil Steril 2005.

In the United States, the success rate after transfer of fresh embryos from donor oocytes is considerably higher than that after transfer of fresh embryos from nondonor oocytes (47% vs. 33% live birth per ET) (1); this pattern is also observed, although to a lesser extent, in European countries (33% vs. 29% clinical pregnancy per ET) (2). However, in Canada, the success rates of the two types of procedures are very similar (33% vs. 34% pregnancy and 26% vs. 28% live birth per ET). Differences in patient populations or variable rates in the Canadian data due to small sample size (only 263 fresh ETs from donor oocytes were performed in 2001) might explain these discrepancies among countries.

One issue of great concern to all providers and consumers of ART is that of multiple pregnancy. Although it is not the role of CARTR to encourage its member centers to reduce their multiple pregnancy rates through limiting the number of embryos transferred, it is our responsibility to provide data to inform centers about the situation in Canada. Whereas many policy makers, in Europe especially, are pushing for single-embryo transfers to virtually eliminate multiple pregnancy, in Canada, more than half of fresh ETs in 2001 involved three or more embryos. There was only a handful of elective single-embryo transfers performed in 2001, but elective double-embryo transfers represented approximately one quarter of fresh ETs performed in that year.

Another issue of hot debate at the present time is that of the best outcome measure for evaluating the success of ART cycles. The traditional measures of clinical pregnancy and live birth per cycle started have been criticized because they do not provide information about multiple pregnancies or births, which are considered adverse and undesirable outcomes. Usually, a center with high pregnancy and live birth rates also has high multiple pregnancy rates, whereas another center that makes an effort to reduce multiple pregnancy rates, especially those of triplets and quadruplets, by limiting the number of embryos transferred to one or two, might pay the price by having a decrease in their pregnancy and birth rates. In a competitive environment, such a situation could result in loss of business for that center. To level the playing field, the outcome “singleton live birth” has been suggested as the measure of success of ART treatment. In this report, we have included singleton live birth as an outcome, as well as the more conventional outcomes measures.

In summary, the Canadian ART Register has been successful, within 2 years of its inception, in recruiting 86% of Canadian clinics to participate voluntarily in a compilation of ART cycles in Canada. Pregnancy rates per cycle started of 28% in IVF/ICSI cycles and 19% in FET cycles, and live birth rates of 23% and 15%, respectively, compare favorably with rates around the world.

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Acknowledgments 

The authors thank the personnel from each center responsible for data entry for CARTR for their hard work and devotion to detail.

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APPENDIX. 

Canadian ART Centers Reporting Data to CARTR for 2001 

University of British Columbia IVF Program, Vancouver, British Columbia

Genesis Fertility Center, Vancouver, British Columbia

Foothills Regional Fertility Program, Calgary, Alberta

Assisted Reproductive Technology at University of Saskatchewan (ARTUS), Saskatoon, Saskatchewan

Heartland Fertility Clinic, Winnipeg, Manitoba

London Health Sciences Center, London, Ontario

Hamilton Health Sciences Center for Reproductive Care, Hamilton, Ontario

ISIS Regional Fertility Center, Mississauga, Ontario

Sunnybrook Women’s College Hospital Fertility Center, Toronto, Ontario

Success Through Assisted Reproductive Technology (START), Toronto, Ontario

Toronto Fertility Sterility Institute (TFSI), Toronto, Ontario

Mt. Sinai Reproductive Biology Unit, Toronto, Ontario

Toronto Center for Advanced Reproductive Technology (TCART), Toronto, Ontario

LIFE Program, Toronto, Ontario

IVF Canada, Scarborough, Ontario

Markham Fertility Center, Markham, Ontario

The Fertility Center at the Ottawa Hospital, Ottawa, Ontario

Conceptia Clinic, Moncton, New Brunswick

Reproductive Endocrine Center, Halifax, Nova Scotia

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References 

1. Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology . 2001 assisted reproductive technology success rates . Atlanta, Georgia: U.S. Department of Health and Human Services; 2003; Available at: www.cdc.gov/reproductivehealth/ART01/index.htm. Accessed Aug. 11, 2004.
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2. Nyboe Andersen A , Gianaroli L , Felberbaum R , de Mouzon J , Nygren KG  European IVF-monitoring programme . European Society of Human Reproduction and Embryology. Assisted reproductive technology in Europe, 2001. Results generated from European registers by ESHRE . Hum Reprod . 2005;20:1158–1176
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