- Email: [email protected]
In vitro fertilization-embryo transfer in the United States: 1988 results from the IVF-ET Registry*
FERTILITY AND STERILITY
Vol. 53, No.1, January 1990
Printed on acid-free paper in U.S.A.
Copyright© 1990 The American Fertility Society
In vitro fertilization-embryo transfer in the United States: 1988 results from the IVF-ET Registry* Medical Research Internationalt and the Society for Assisted Reproductive Technology, The American Fertility Society Burlington, Massachusetts and Birmingham, Alabama
This is the third annual report of the U.S. Registry of in vitro fertilization-embryo transfer (IVF-ET) and related practices. The present report describes the 1988 experiences of 135 U.S. member clinics with respect to treatments and outcomes. During 1988 the clinics reported performing 22,649 ovarian stimulation cycles, with 3,508 (15%) resulting in a clinical pregnancy and 2,627 (12%) in a live delivery. Ninety-three percent of the clinics had at least one delivery, and overall a total of 3,427 babies were born. The overall live delivery rates were 12% for IVF (based on 13,64 Tretrievals), 21% for gamete intrafallopian transfer (GIFT) (based on 3,080 retrievals), and 20% for IVF and GIFT in combination (based on 671 retrievals). In addition to these treatments, detailed results are presented for zygote intrafallopian transfer, frozen embryo transfers, and IVF of donated oocytes. Fertil Steril53:13, 1990
The assisted reproductive technologies continue to be increasingly important treatments for infertility. The expanding use and results of these technologies must be documented to understand not only their clinical effects, but to also measure their public health impact. 1 The significance of these and other related issues was emphasized in a U.S. congressional subcommittee hearing. 2 Among the concerns raised were monitoring these advanced infertility treatments and reporting accurate statistics on both practices and outcomes. One mechanism for performing these activities involves patient registration in a multicenter effort. 3 The U.S. In Vitro Fertilization (IVF) Registry was established as a collaborative effort between The Society for Assisted Reproductive Technology (SART) of The American Fertility Society (AFS) and Medical Research International (MRI). A major goal of the Registry is to explore the epidemiology of the assisted reproductive technologies. The Registry's data collection efforts were impleReceived October 4, 1989.
* Supported by a contract from Serono Laboratories, Inc., Norwell, Massachusetts, 02061. t Reprint requests: Stuart C. Hartz, Sc.D., Medical Research International, Inc., Six New England Executive Park, Burling· ton, Massachusetts 01803. Vol. 53, No.1, January 1990
mented in January, 1987, and its first two reports summarized the 1985 and 1986 results from 41 U.S. clinics4 and the 1987 results from 96 U.S. clinics, 5 respectively. The Registry's membership currently includes 174 clinics in 40 states and the District of Columbia. This report describes the 1988 IVF and related practices and outcomes of 135 U.S. member clinics (listed below). The Registry's current reporting period includes stimulation cycles and transfer procedures initiated in 1988. Pregnancies conceived in 1988 were followed up through October, 1989 to determine their outcomes. MATERIALS AND METHODS
This report summarizes the following treatments: IVF, embryo transfer (ET), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), and frozen ET, and IVF with donated oocytes. Throughout the report when referring to the entire group of treatments, the term IVF-ET will be used. Details of the data collection procedures and software designed by MRI are described in the previous reports. 4 •5 Registry members collect and forMRI and AFS
IVF-ET in the U.S. during 1988
13
ward their data using either (1) RecordKeeper, a PC-based system designed for IVF-ET clinics that records patient specific information, or (2) a set of data forms that summarizes each clinic's treatment and outcome results. The current report includes data from 50 clinics using RecordKeeper, as well as 85 that submitted data via paper forms. There were 41% more clinics reporting 1988 results than had reported for 1987. In addition, more than twice as many clinics reported via RecordKeeper than in 1987. Of the 22,649 stimulation cycles, 16,636 (73%) were reported via the paper data forms and the remainder on disks created with RecordKeeper. The treatments and the results for IVF-ET cycles initiated in 1988 are presented either (1) as summary statistics using the pooled results from both data forms and floppy disks, (2) or as more detailed analyses using the individual patient records submitted via disks only. Unless stated otherwise, each analysis is based on the pooled resul~s combining both paper form and disk information.
RESULTS In 1988, the 135 clinics initiated 22,649 stimulation cycles in 16,195 women. Seventy-eight percent (17,753) of the cycles resulted in an oocyte retrieval. Of the 135 clinics, 126 (93%) reported at least one live delivery. The IVF-ET treatments described below resulted in 3,508 clinical pregnancies and 2,627 live deliveries. There were 3,427 babies born, including 580 sets of twins, 100 triplets, 11 quadruplets, and 3 quintuplets. For babies whose sex was known, the male:female ratio was 1,635:1,534 or 1.06. (There were 59 clinical pregnancies with unknown outcome as of October 31, 1989.) Hyperstimulation with negative beta-human chorionic gonadotropin ({3-hCG) was reported in 25 (0.1%) stimulation cycles and with positive {3-hCG in30 (0.1%). In Vitro Fertilization
In 1988 each of the 135 clinics reported performing IVF. The clinics reported 13,647 IVF retrievals, of which 1,801 (13%) were by laparoscopy, 11,678 (86%) by ultrasound, 164 (1%) by a combination of laparoscopy and ultrasound, and 4 by laparotomy. Table 1 provides the distributions of selected outcomes by number of IVF retrievals. The maximum number of retrievals reported by a clinic was 964. A total of 2,243 clinical pregnancies (de14
MRI and AFS IVF-ET in the U.S. during 1988
fined by rising {3-hCG and the presence of gestational sac(s) on ultrasound) were conceived through IVF. An ET resulted from 11,821 (87%) of retrievals. The maximum number ofETs performed by a single clinic was 888. The overall clinical pregnancy and delivery rates per· ET were 19% and 14%, respectively. The clinical pregnancy rates by number of transfer cycles were 20% (70/342) for <25 cycles, 18% (617 /3504) for 25 to 99 cycles, 19% (621/3229) for 100 to 199 cycles, and 20% (935/4746) for 200 or more cycles. The corresponding delivery rates were 14%, 13%, 14%, and 14%, respectively. Three clinics each had more than 100 clinical pregnancies and accounted for 507 (23%) of all clinical pregnancies. Seventy (52%) of the clinics reported <10 pregnancies, while overall124 (92%) clinics reported at least one clinical pregnancy usingiVF. Of the clinical pregnancies, 1,657 (74%) resulted in a live delivery, of which 13% were reported to be preterm. The Registry defines deliveries (preterm as live births occurring before 36 weeks gestation, and term as live births occurring thereafter) in the reporting year in which conception occurred. (As of October 31, 1989, the outcomes of 43 pregnancies were still unknown.) Among the 16 clinics not reporting a delivery, the maximum number of retrievals was 28. Three clinics accounted for 23% of the deliveries as aresult ofiVF. Also, 38 (28%), 62 (46%), and 19 (14%) of the clinics had delivery rates (per retrieval) between 1% and 9%, 10% to 19%, and 20% to 36%, respectively. The clinic reporting the maximum delivery rate (36%) performed 14 retrievals. There were 2,133 babies born including 919 resulting from 421 multiple births. Overall, 19% of the clinical pregnancies resulted in a multiple delivery: 356 twin, 55 triplet, 8 quadruplet, and 2 quintuplet deliveries. In addition to the 532 reported (spontaneous) abortions given in Table 1, there were 20 stillbirths and 15 therapeutic abortions recorded. The Registry defines a (spontaneous) abortion as a clinical pregnancy loss occurring before a gestational age of 20 weeks and a stillbirth as the birth of a nonviable fetus of 20 weeks gestation or more. The clinical pregnancy and delivery rates increased with the average number of embryos transferred per cycle. The clinical pregnancy and delivery rates ranged from 16% and 12% for an average of <3 embryos transferred to 22% and 16% for 4 or more embryos transferred, respectively. In addition, the rate of multiple deliveries increased from Fertility and Sterility
Table 1
IVF Treatment Outcome by Total Number of Retrieval Cycles
IVF cycles
No. of clinics
No. of retrievals
<25 25 to 99 100 to 199 >199
32 59 30 14
339 3,310 4,077 5,921
135
13,647
Total
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies'
(19) (15) (17) (17)
18 (29) 116 (23) 148 (22) 250 (25)
2 (3) 30 (6) 36 (5) 48 (5)
2,243 (16)
532 (24)
116 (5)
63 500 686 994
No. of all deliveries d 43 383 511 720
(13) (12) (13) (12)
1,657 (12)
" Clinical pregnancy rates are expressed in parentheses as a percent of retrievals. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies.
' Ectopic pregnancy rates are expressed in parentheses as a percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of retrievals.
2.8% to 4.3%, respectively. Only 3 clinics reported transferring on average more than 5 embryos per cycle, with a maximum of 5.3 An analysis of the 2,623 ET cycles recorded through RecordKeeper by 50 clinics also indicated that the clinical pregnancy rate increased with the number of embryos transferred. The clinical pregnancy rate ranged from 4% (12/332) for 1 embryo transferred to 22% (132/609) for 5 or more embryos transferred per cycle. In addition, the rates of multiple deliveries varied with the number of embryos transferred-from 0.3% (2/749) for 2 or fewer embryos transferred to 5.4% (33/609) for 5 or more embryos transferred. Fifty-six (41%) clinics reported administering a gonadotropin-releasing hormone (GnRH) analog as part of their most commonly used stimulation regimens. In addition, the outcomes of 2,623 ET cycles reported via RecordKeeper were also evaluated according to stimulation protocol (Table 2). The most frequently used stimulation regimen was human menopausal gonadotropin (hMG) with clo-
miphene citrate, followed by hMG alone, and hMG and a GnRH analog. The pregnancy and delivery rates, 21% and 15% respectively, were highest for the protocol including the combination hMG, follicle-stimulating hormone (FSH), and a GnRH analog. Table 3 shows the outcomes of the above 2,623 ET cycles by age of the woman receiving treatment. The clinical pregnancy and delivery rates declined steadily with age. In women 45 years or older there were 7 ET cycles resulting in 1 clinical pregnancy, which ended in a spontaneous abortion. Table 4 presents cancellation, clinical pregnancy, and delivery rates for IVF and GIFT by selected diagnoses for cycles submitted through RecordKeeper. The cancellation rate was highest for women with unexplained infertility and lowest for those with tubal disease. For IVF, the clinical pregnancy and delivery rates were highest for couples with male immune problems. Sixteen chromosomal abnormalities were reported. These included 1 trisomy 13, 2 trisomy 16,
Table2
Outcome by Stimulation Protocol and Procedure IVF
Stimulation protocol
No. of cycles
No. of canceled cycles"
No. of ETcycles
GIFT
No. of clinical pregnancies b
No. of multiple deliveries'
No. of transfer cycles
No. of clinical pregnancies d
No. of multiple deliveries e
(31) (18) (32) (33)
554 479 559 364
100 (18) 81 (17) 63 (11) 47 (13)
19 (3.4) 24. (5.0) 10 (1.8) 6 (1.6)
149 240 122 143
915 527
207 (23) 181 (34)
476 191
101 (21) 30 (16)
14 (2.9) 7 (3.7)
77 62
21 (27) 13 (21)
7 (9.1) 6 (9.7)
6,013
1,690 (28)
2,623
422 (16)
80 (3.1)
793
215 (27)
57 (7.2)
HMGalone HMG, GnRH analog HMG, clomiphene HMG,FSH HMG, FSH, GnRH analog Other combinations
1,217 1,061 1,275 1,018
Total
374 193 404 331
a A cycle is defined as canceled if no retrieval is performed. Values in parentheses are expressed as percent. b Clinical pregnancy rates are expressed in parentheses as a percent of ET cycles. 'Multiple delivery rates are expressed in parentheses as a
Vol. 53, No.1, January 1990
55 53 28 45
(37) (22) (23) (31)
13 14 7 10
(8.7) (5.8) (5.7) (7.0)
percent of ET cycles. d Clinical pregnancy rates are expressed in parentheses as a percent of G 1FT transfer cycles. e Multiple delivery rates are expressed in parentheses as a percent of G 1FT transfer cycles.
MRI and AFS
IVF-ET in the U.S. during 1988
15
TableS
In Vitro Fertilization Treatment Outcome by Woman's Age No. of ETcycles
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnanciesc
No. of all deliveries d
<25 25to 29 30to34 35to 39 40+ Unknown
25 397 1,091 904 198 8
10 (40) 75 (19) 181 (17) 135 (15) 20 (10) 1 (13)
0 (0) 24 (32) 39 (22) 32 (24) 12 (60) 0 (0)
1 (9) 5 (6) 7 (4) 5 (4) 1 (5) 0 (0)
10 (40) 53 (13) 147 (13) 99 (11) 8 (4) 1 (13)
45 (4.1) 17 (1.9) 4 (2.0) 0 (0)
Total
2,623
422 (16)
107 (25)
19 (4)
318 (12)
80 (3.0)
Age
No. of multiple deliveries e
y
3 (12.0) 11 (2.8)
a Clinical pregnancy rates are expressed in parentheses as a percent of ET cycles. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies. c Ectopic pregnancy rates are expressed in parentheses as a
percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of ET cycles. e Multiple delivery rates are expressed in parentheses as a percent of ET cycles.
1 trisomy 18, 4 trisomy 21, and 1 trisomy 22; there were also 1 triploid, 3 tetraploid, 1 Mosaic 45-46 and 1 XYY syndrome (twins), and 1 Tetralogy of Fallot in a twin delivery. Except for one trisomy 21, these resulted in either a spontaneous or therapeutic abortion. There were 23 different reported congenital malformations in 18 pregnancy outcomes. These included 7 reported outcomes with 9 central nervous system (CNS) malformations (spina bifida and hydrocephalus (2) terminated in therapeutic abortion, hydrocephalus, microcephalus, corpus callosum, Klippel-Feil syndrome, cranial synostosis terminated in spontaneous abortion), 2 outcomes with 3 cardiovascular malformations (aortic stenosis and ventricle septal defect, hydroplastic left
ventricle defect), 5 outcomes with 6 gastrointestinal malformations (tracheal-esophageal fistula and renal atresia, tracheal-esophageal fistula (2), tracheal fistula, imperforate anus), 1 genitourinary (unilateral hydronephrosis), 2 respiratory tract (cleft palate (2)), 1 musculoskeletal (clubfoot), 2 eye (coloboma in twins), and 1 skin (hemangiomaunspecified). The known maternal ages ranged from 24 to 39 years. Except for the 3 outcomes cited above, these pregnancies resulted in liveborn outcomes.
Table 4
Gamete Intrafallopian Transfer
There were 101 clinics that performed GIFT alone (i.e., not in conjunction with IVF) in 3,080
Outcome by Infertility Diagnosis and Treatment IVF
Infertility diagnosis a Tubal disease/ problem 6 Female unexplained Female immune Endometriosis Male unexplained Male immune Male sperm abnormalities h
No. of stimulation cycles
No. of canceled cyclesb
No. of embryo transfers
No. of clinical pregnanciesc
No. of all deliveriesd
No. of transfer cycles
No. of clinical pregnancies•
No. of all deliveries'
3,102 642 237 2,021 291 207
979 (32) 345 (54) 82 (35) 997 (49) 124 (43) 68 (33)
1,803 172 116 682 107 103
282 (16) 24 (14) 15 (13) 104 (15) 10 (9) 26 (25)
211 (12) 17 (10) 11 (9) 75 (11) 8 (7) 20 (19)
104 180 33 386 62 31
15 (14) 43 (24) 11 (33) 103 (27) 16 (26) 7 (23)
13 (12) 43 (24) 9 (27) 80 (21) 14 (23) 6 (19)
1,287.
525 (41)
496
78 (16)
55 (11)
188
46 (24)
38 (20)
a Represents cycle with specific diagnosis indicated. Patient may be represented in more than one category. b A cycle is defined as canceled if no retrieval is performed. Values in parentheses are expressed as percent. c Clinical pregnancy rates are expressed in parentheses as a percent of ET cycles. d Delivery rates (live) are expressed in parentheses as a percent of ET cycles.
16
MRI and AFS
GIFT
IVF-ET in the U.S. during 1988
e Clinical pregnancy rates are expressed in parentheses as a percent of G 1FT transfer cycles. f Delivery rates (live) are expressed in parentheses as percent of G 1FT transfer cycles. 6 Tubal disease or problem including previous tubal surgery, tubal ligation, absence oftube(s). h Includes oligospermia, asthenospermia, and teratospermia.
Fertility and Sterility
Table 5
Gamete Intrafallopian Transfer Outcome by Total Number of GIFT Retrievals Performed
GIFT cycles
No. of clinics
No. of GIFT retrievals
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies'
No. of all deliveries d
<25 25 to 99 >99
65 29 7
416 1,336 1,328
88 (21) 390 (29) 368 (28)
17 (19) 80 (21) 74 (20)
0 (0) 21 (5) 21 (5)
71 (17) 302 (23) 281 (21)
101
3,080
846 (27)
171 (20)
42 (5)
654 (21)
Total
a Clinical pregnancy rates are expressed in parentheses as a percent of retrievals. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies.
' Ectopic pregnancy rates are expressed in parentheses as a percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of retrievals.
retrieval cycles. Table 5 gives the treatment results by number of GIFT retrieval cycles. Of the clinics performing GIFT, 30 (30%) did not report a delivery. However, in this group the maximum number of retrievals performed was 13, and 29 of the clinics performed <10 retrievals. Excluding clinics with <10 retrievals, the maximum reported delivery rate was 43%. Two clinics reported >200 GIFT treatments. There were 846 (27%) GIFT cycles that resulted in a clinical pregnancy. Seventy-six (75%) clinics had at least one clinical pregnancy, and of these, 54 (71%) had <10 pregnancies. There were 5 clinics that had 40 or more pregnancies, accounting for 316 (37%) of the total reported. The spontaneous abortion rate associated with GIFT was 20%. Fifteen stillbirths were also recorded. Four clinics accounted for 218 (33%) of the 654 deliveries. There were 892 babies delivered, including 159 sets of twins, 34 triplets, 3 quadruplets, and 1 quintuplet. In addition, there were 98 (15%) preterm deliveries. (There were 9 clinical pregnancies whose outcomes were unknown as of October 31, 1989). Table 6 presents outcomes of the GIFT procedure by age of the patient using RecordKeeper data. Clinical pregnancy and delivery rates decreased with the age of the woman. Of the 148 cycles in women <30 years of age, 13 were in women <25, and resulted in 4 deliveries. Also, there were 10 cycles in women 45 years or older, none of which resulted in a clinical pregnancy. Table 2 presents the outcomes of 793 GIFT transfer cycles according to stimulation protocol. The pregnancy and delivery rates, 37% and 31%, respectively, were highest for the protocol including hMG alone. Table 4 presents the outcome of GIFT by infertility diagnosis. The highest rates of clinical pregnancy and delivery were in women with immune
problems. The lowest rates were in women with tubal problems. Nine chromosomal abnormalities were reported. These included 1 trisomy 13, 2 trisomy 15, 2 trisomy 18, 3 trisomy 21, 1 XYY syndrome, and 1 Turner syndrome. The Turner syndrome resulted in a spontaneous abortion, and all others in therapeutic abortions. There were six reported congenital malformations in four pregnancy outcomes. These included one stillborn with anencephaly, one kidney (unspecified) in a liveborn, one congenital heartblock in a liveborn, and one stillborn with multiple malformations (spina bifida, clubfoot, and hypospadias).
Vol. 53, No.1, January 1990
GIFT In Combination With IVF
Fifty-nine (44%) of the 135 clinics reported using GIFT in combination with IVF. There were 671 oocyte retrievals of which 171 (25%) resulted in a clinical pregnancy and 136 (20%) in a delivery. Five of the clinics performed 326 (49%) of the combined procedures. Of the 671 retrievals, 577 (86%) were performed using laparoscopy. The 136 deliveries resulted in 172live babies, including 27 sets of twins, and 5 triplets. In addition, there was a 13% preterm delivery rate. (As of October 31, 1989, there were 3 pregnancies whose outcomes were unknown to the Registry.) There was one outcome with a reported congenital malformation: anencephaly resulting in a therapeutic abortion. Zygote Intrafallopian Transfer (ZIFT) and Related Procedures
Twenty clinics performed 385 stimulation cycles using ZIFT or a similar procedure (i.e., pronuclear stage tubal transfer (PROST), tubal embryo transfer (TET), tubal pre-embryo transfer (TPET), collectively referred to as ZIFT). Of these cycles, 355 MRI and AFS
IVF-ET in the U.S. during 1988
17
TableS
Gamete lntrafallopian Transfer Treatment Outcome by Woman's Age No. of GIFT cycles
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies •
No. of all deliveries d
No. of multiple deliveries e
<30 30to 34 35to 39 40+ Unknown
148 327 222 92 4
52 (35) 96 (29) 51 (23) 13 (14) 3 (75)
7 (13) 13 (14) 15 (29) 5 (38) 2 (67)
2 (4) 6 (6) 2 (4) 0 (O) 0 (0)
46 (31) 83 (25) 37 (17) 8 (9) 1 (25)
14 (9.5) 31 (9.5) 10 (4.5) 2 (2.2) 0 (0)
Total
793
215 (27)
42 (20)
10 (4)
175 (22)
57 (7.2)
Age y
• Clinical pregnancy rates are expressed in parentheses as a percent of G 1FT cycles. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies. • Ectopic pregnancy rates are expressed in parentheses as a
percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of G1FT cycles. • Multiple delivery rates are expressed in parentheses as a percent of G 1FT cycles.
(92%) resulted in an oocyte retrieval, and 275 (71%) in a transfer cycle. Six of the clinics performed 20 or more retrievals for ZIFT. Of the 355 retrievals, 97 (27%) resulted in a clinical pregnancy and 71 (20%) in a delivery. Of the 71 deliveries, 3 (4%) were preterm. Ninety-eight live babies, including 19 sets of twins and 4 triplets, were delivered. (As of October 31, 1989, there was 1 pregnancy whose outcome was unknown to the Registry.) There were no reported chromosomal abnormalities or congenital anomalies for ZIFT.
were unknown to the Registry.) In addition, there were 2,4 74 patients whose IVF cycles resulted in freezing 9,605 embryos, or 3.9 per patient. There was one liveborn with aortic atresia and other reported anomalies.
Frozen Embryo Transfers
There were 1,025 frozen ET cycles performed in 67 clinics. Four of the clinics performed 50 or more such cycles, with a reported maximum of 103 transfer cycles. These four clinics accounted for 48% of the clinical pregnancies, and 49% of the deliveries. Twenty-eight (42%) of the clinics had at least 1 clinical pregnancy. Table 7 details the distribution of selected outcomes by number of frozen embryo transfer cycles. Included in the 73 deliveries were 7 sets of twins and 1 set of triplets. (As of October 31, 1989, there were 2 pregnancies whose outcomes Table 7
In 1988, 26 clinics reported performing IVF-ET with donated oocytes. There were 130 patients who underwent 158 donor transfers. Fifty-one (32%) of the donor transfers produced a clinical pregnancy. Thirty-six (23%) live deliveries resulted, including 12 sets of twins and 1 set oftriplets. (As of October 31, 1989 there was 1 pregnancy whose outcome was unknown.) There were no reported chromosomal abnormalities or congenital anomalies with this procedure. DISCUSSION
This report summarizes the IVF-ET results of 135 IVF Registry clinics in the U.S. There was a 41% increase over 1987 in clinics reporting their data to the Registry. In addition more than twice
Treatment Outcome by Number of Frozen Embryo Transfer Cycles
Frozen embryo transfer cycles
No. of clinics
<25 25to49 50+
54 9 4
Total
67
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies•
No. of all deliveries d
396 307 322
25 (6) 26 (8) 50 (15)
4 (16) 7 (27) 12 (24)
1 (4) 2 (7) 2 (4)
18 (5) 19 (6) 36 (11)
1,025
101 (10)
23 (23)
5 (5)
73 (7)
No. of transfer cycles
a Clinical pregnancy rates are expressed in parentheses as a percent of transfer cycles. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies.
18
IVF of Donated Oocytes
MRI and AFS
IVF-ET in the U.S. during 1988
• Ectopic pregnancy rates are expressed in parentheses as a percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of transfer cycles.
Fertility and Sterility
as many clinics reported their results via RecordKeeper. Although there were changes in the practice of IVF-ET, there is a reassuring consistency between the 1987 and 1988 data received by the Registry. In 1988 the number of stimulation cycles reported increased by 55% over 1987. In addition, the percent of retrieval cycles for the combination IVF and GIFT procedure doubled over that reported in the last year. Also, the ZIFT procedure was reported to the Registry for the first time this year by a number of clinics. There was a marked increase in the percent of retrievals for IVF that were performed by ultrasound. In 1987, 57% of retrievals were by ultrasound, whereas in 1988, 86% were by ultrasound. The clinical pregnancy rate per retrieval for IVF remained at 16%, as it was in 1987. For GIFT the pregnancy rate increased slightly from 25% to 27%. The rates of multiple birth were similar to the previous year's: 3.1% for IVF and 6.4% for G 1FT, compared with 2.7% and 5.2% for 1987. There were more than twice as many frozen ET cycles as reported in 1987. The clinical pregnancy rate was 10% for both years. In this report outcomes of IVF and G 1FT treatment by infertility diagnosis were presented. The numbers in some categories were somewhat small, because these data were not recorded by all clinics using RecordKeeper. Therefore, the numbers do not necessarily reflect all subjects with a particular diagnosis. However, these results do provide important information. It is expected that as the Registry's database grows, additional characteristics of IVF and G 1FT practices will be described in future reports. With three years' worth of data, the Registry can now provide a resource for examining trends in numerous areas, including stimulation protocols, retrieval methods, hyperstimulation rates, and occurrence of birth outcomes including congenital malformations and chromosomal abnormalities. Acknowledgments. Medical Research International would like to express its appreciation to the staffs at the IVF /ET clinics for their critical support of The IVF Registry. The clinics located at the following facilities contributed data as of October 1, 1989: Alabama-ART Program at Birmingham, Birmingham; University of Alabama, Birmingham; Arizona-Arizona Fertility Institute, Phoenix; Southwest Fertility Center, Phoenix; California-Alta Bates Hospital, Berkeley; Beverly HillsEncino Fertility Institutes, Encino; UCI-AMI Center for Reproductive Health, Garden Grove; Scripps Clinic Fertility Center, La Jolla; Lorna Linda University, Lorna Linda; Long Beach Memorial Hospital/University of California at Irvine, Long Beach; The Center for Reproductive Medicine at Cedars-Sinai Medical Center, Los Angeles; University of California at Los Vol. 53, No.1, January 1990
Angeles; Institute for Reproductive Research/The Hospital of the Good Samaritan, Los Angeles; Century City Hospital, Los Angeles; USC School of Medicine, Los Angeles; Hoag Fertility Service Center, Newport Beach; Northridge Hospital, Northridge; AMI South Bay Hospital, Redondo Beach; IGO Medical Group of San Diego; Children's Hospital, San Diego; University of California at San Francisco; Pacific Fertility Center, San Francisco; Fertility and Reproductive Health Institute of Northern California, San Jose; Forest Fertility Center, San Jose; Nova Fertility Center, San Mateo; John Muir Hospital, Walnut Creek; Whittier Hospital Medical Center, Whittier; Colorado-Reproductive Genetics In Vitro, P.C., Denver; Infertility, Gynecology and Obstetric Associates, Englewood; Connecticut-Mount Sinai Hospital, Hartford; Yale University School of Medicine, New Haven; Delaware-Medical Center of Delaware at Christiana Hospital, Newark; FloridaShands Hospital, Gainesville; Fertility Institute of Northwest Florida, Gulf Breeze; Memorial Medical Center, Jacksonville; Northwest Center for Infertility and Reproductive Endocrinology, Margate; Sand Lake Hospital IVF Center/Dr. G. W. DeVane, Orlando; Humana Women's Hospital, Tampa; Georgia-Reproductive Biology Associates, Atlanta; Augusta Reproductive Biology Associates, Augusta; Medical College of Georgia, Augusta; Iowa-McFarland Clinic, Ames; University of Iowa Hospitals and Clinics, Iowa City; Illinois-Fertility Center, Chicago; IVF Illinois, Chicago; Mount Sinai Hospital Medical Center, Chicago; Glenbrook Hospital, Glenview; Indiana-Indiana University Hospital, Indianapolis; Pregnancy Initiation Center, Indianapolis; Methodist Hospital, Indianapolis; Kansas-Reproductive Resource Center of Greater Kansas City, Overland Park; Center for Reproductive Medicine, Wichita; Kentucky-The Fertility Institute (Ohio and Kentucky), Fort Thomas; University of Kentucky, Lexington; Norton Hospital, Louisville; Louisiana-Fertility Center of Louisiana, Kenner; Fertility Institute of New Orleans; MarylandThe Johns Hopkins University School of Medicine, Baltimore; University of Maryland, Baltimore; Women's Hospital Fertility Center at Greater Baltimore Medical Center, Baltimore; Montgomery Infertility Institute, Bethesda; Massachusetts-Beth Israel Hospital, Boston; Brigham and Women's Hospital, Boston; Boston IVF, Brookline; Michigan-Center for Reproductive Medicine at Oakwood Hospital, Dearborn; Hutzel Hospital/Wayne State University, Detroit; Blodgett Memorial Medical Center, Grand Rapids; William Beaumont Hospital, Royal Oak; Saginaw General Hospital, Saginaw; Ann Arbor Reproductive Medicine Associates, Ypsilanti; Minnesota-University of Minnesota, Minneapolis; Missouri-International Center for Reproductive Research, Kansas City; Jewish Hospital of St. Louis, St. Louis; Mississippi-University of Mississippi, Jackson; Nebraska-Nebraska Methodist Hospital, Omaha; Nevada-Northern Nevada Fertility Center, Reno; New Hampshire-Dartmouth Hitchcock Medical Center, Hanover; New Jersey-UMDNJ at Newark, Newark; New Mexico-Presbyterian Hospital, Albuquerque; New YorkFertility and Hormone Center/ Albert Einstein College of Medicine, Dobbs Ferry; Columbia Presbyterian Medical Center, New York City; Cornell University Medical Center, New York City; Mount Sinai Medical Center, New York City; IVF Australia Prggram/United Hospital, Port Chester; Long Island IVF, Port·Jefferson; Institute for Reproductive Health and Infertility, Rochester; University of Rochester, Rochester; SUNY Health Science Center/Crouse Irving Memorial Hospital, Syracuse; North Carolina-University of North Carolina School of Medicine, Chapel Hill; Center for Reproductive Medicine, MRI and AFS
IVF-ET in the U.S. during 1988
19
Charlotte; Duke University Medical Center, Durham; North Dakota-Centennial Medi.:al Center, Minot; Ohio-Akron City Hospital, Akron; Bethesda Fertility Center, Cincinnati; Cleveland Clinic Foundation, Cleveland; Midwest Reproductive Institute, Columbus; Ohio State University, Columbus; Miami Valley Hospital Fertility Center, Dayton; OklahomaBennett Fertility Institute, Oklahoma City; Hillcrest Fertility Center, Tulsa; Oregon-Oregon Health Science Center, Portland; Pennsylvania-St. Luke's Hospital, Bethlehem; Christian Fertility Institute, Easton; Endocrine Histology Associates, Melrose Park; Albert Einstein, North Division, Philadelphia; Hospital of the University of Pennsylvania, Philadelphia; Pennsylvania Reproductive Associates at Pennsylvania Hospital, Philadelphia; Magee-Women's Hospital, Pittsburgh; Shadyside Hospital, Pittsburgh; Women's Clinic Limited, W. Reading; Rhode Island-Women and Infants' Hospital, Providence; South Carolina-Medical University of South Carolina, Charleston; Southeastern Fertility Center, Mt. Pleasant; Tennessee-Humana East Ridge Hospital, Chattanooga; University of Tennessee, Knoxville; Vanderbilt University Medical Center, Nashville; Texas-St. David's Community Hospital, Austin; Trinity IVF/ET, Carrollton; University of Texas Southwestern Medical Center, Dallas; Fort Worth Infertility Center, Fort Worth; Baylor IVF Program, Houston; University of Texas Medical School, Houston; Fertility Program at Methodist Hospital, San Antonio; Utah-University of Utah, Salt Lake City; Virginia-Genetics & IVF Institute, Fairfax; The Howard and Georgeanna Jones Institute for Reproductive Medicine, Norfolk; Henrico Doctors' Hospital IVF/GIFT Program, Richmond; Medical College of Virginia, Richmond; Washington-Swedish Hospital Medical Center, Seattle; University of Washington, Seattle; Washington, D.C.-Columbia Hospital for Women Medical Center; George Washington University Medical Center; Wisconsin-Appleton Medical Center, Appleton; University of Wisconsin Clinics, Madison; Advanced Institute of Fertility, Milwaukee; Medical College of Wisconsin, Milwaukee. REFERENCES 1. U.S. Congress, Office of Technology Assessment: Infertil-
2.
3. 4.
5.
ity: Medical and Social Choices. OTA-BA-358, Washington, D.C., U.S. Government Printing Office, May, 1988 Subcommittee on Regulation, Business Opportunities, and Energy, Committee on Small Business, House of Representatives: Consumer Protection Issues Involving In Vitro Fertilization Clinics. Serial No. 101-05, Washington, D.C., U.S. Government Printing Office, March, 1989 DeCherney AH, Hartz SC: Assisted reproduction: registration vis-a-vis regulation. Fertil Steril 51:68, 1989 Medical ReRearch International, The American Fertility Society Special Interest Group: In vitro fertilization/embryo transfer in the United States: 1985 and 1986 results from the National IVF-ET Registry. Fertil Steril 49:212, 1988 Medical Research International, The American Fertility Society Special Interest Group: In vitro fertilization/embryo transfer in the United States: 1987 results from the National IVF-ET Registry. Fertil Steril51:13, 1989
Laboratories, the American Fertility Society and SART. Once again, this report from MRI has demonstrated the dramatic increase in the number and types of Assisted Reproductive Technology (ART) treatments performed in the United States. The initial report from the Registry, covering the years 1985 and 1986, detailed 5,253 IVF cycles for the 2 years that resulted in a total of 568 babies born: In 1987 there were 14,647 IVF cycles that resulted in 1,858 babies. The present report covering 1988 includes 22,649 IVF stimulation cycles with 3,427 babies born. Both prior reports included IVF, GIFT, frozen ETs and pregnancies using donated oocytes. The 1988 report now includes also ZIFT and related procedures. Even more impressive is the increase in the number of IVF Clinics in the United States that are voluntarily contributing their data to the Registry. In 1985 there were 30 reporting clinics; in 1986 there were 41 reporting clinics; in 1987 there were 96 reporting clinics and 1988 includes data from 135 member clinics. Most importantly, the 1988 Registry data demonstrated that 93% of the United States IVF clinics produced at least one live-born child in 1988, thus soundly refuting the claims made previously that over half the United States IVF programs have failed to produce a single successful pregnancy. In 1989 a Congressional Subcommittee hearing was held at which the results of a questionnaire survey of U.S. IVF and GIFT clinics were presented. The statistical methodology used for that report was criticized on a number of grounds. This report from the Registry provides data that is statistically more valid in that there are equal reporting periods for all programs, deliveries are counted for the year in which the treatment was initiated, and data are given only for pregnancies in which the outcome is known. The Congressional Subcommittee report, however, did provide clinic-specific statistics that had not previously been available. The statistical group at MRI is to be commended on their meticulous and painstaking collection, analysis and reporting of the annual data on the United States ART treatments. Hopefully in the future the Registry will serve the dual purpose of providing scientific analysis as well as clinic-specific results.
COMMENT
This paper is the third report from the United States IVF Registry, a joint project of MRI, Serono
20
MRI and AFS
IVF-ET in the U.S. during 1988
Martin M. Quigley, M.D. President, SART
Fertility and Sterility
Vol. 53, No.1, January 1990
Printed on acid-free paper in U.S.A.
Copyright© 1990 The American Fertility Society
In vitro fertilization-embryo transfer in the United States: 1988 results from the IVF-ET Registry* Medical Research Internationalt and the Society for Assisted Reproductive Technology, The American Fertility Society Burlington, Massachusetts and Birmingham, Alabama
This is the third annual report of the U.S. Registry of in vitro fertilization-embryo transfer (IVF-ET) and related practices. The present report describes the 1988 experiences of 135 U.S. member clinics with respect to treatments and outcomes. During 1988 the clinics reported performing 22,649 ovarian stimulation cycles, with 3,508 (15%) resulting in a clinical pregnancy and 2,627 (12%) in a live delivery. Ninety-three percent of the clinics had at least one delivery, and overall a total of 3,427 babies were born. The overall live delivery rates were 12% for IVF (based on 13,64 Tretrievals), 21% for gamete intrafallopian transfer (GIFT) (based on 3,080 retrievals), and 20% for IVF and GIFT in combination (based on 671 retrievals). In addition to these treatments, detailed results are presented for zygote intrafallopian transfer, frozen embryo transfers, and IVF of donated oocytes. Fertil Steril53:13, 1990
The assisted reproductive technologies continue to be increasingly important treatments for infertility. The expanding use and results of these technologies must be documented to understand not only their clinical effects, but to also measure their public health impact. 1 The significance of these and other related issues was emphasized in a U.S. congressional subcommittee hearing. 2 Among the concerns raised were monitoring these advanced infertility treatments and reporting accurate statistics on both practices and outcomes. One mechanism for performing these activities involves patient registration in a multicenter effort. 3 The U.S. In Vitro Fertilization (IVF) Registry was established as a collaborative effort between The Society for Assisted Reproductive Technology (SART) of The American Fertility Society (AFS) and Medical Research International (MRI). A major goal of the Registry is to explore the epidemiology of the assisted reproductive technologies. The Registry's data collection efforts were impleReceived October 4, 1989.
* Supported by a contract from Serono Laboratories, Inc., Norwell, Massachusetts, 02061. t Reprint requests: Stuart C. Hartz, Sc.D., Medical Research International, Inc., Six New England Executive Park, Burling· ton, Massachusetts 01803. Vol. 53, No.1, January 1990
mented in January, 1987, and its first two reports summarized the 1985 and 1986 results from 41 U.S. clinics4 and the 1987 results from 96 U.S. clinics, 5 respectively. The Registry's membership currently includes 174 clinics in 40 states and the District of Columbia. This report describes the 1988 IVF and related practices and outcomes of 135 U.S. member clinics (listed below). The Registry's current reporting period includes stimulation cycles and transfer procedures initiated in 1988. Pregnancies conceived in 1988 were followed up through October, 1989 to determine their outcomes. MATERIALS AND METHODS
This report summarizes the following treatments: IVF, embryo transfer (ET), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), and frozen ET, and IVF with donated oocytes. Throughout the report when referring to the entire group of treatments, the term IVF-ET will be used. Details of the data collection procedures and software designed by MRI are described in the previous reports. 4 •5 Registry members collect and forMRI and AFS
IVF-ET in the U.S. during 1988
13
ward their data using either (1) RecordKeeper, a PC-based system designed for IVF-ET clinics that records patient specific information, or (2) a set of data forms that summarizes each clinic's treatment and outcome results. The current report includes data from 50 clinics using RecordKeeper, as well as 85 that submitted data via paper forms. There were 41% more clinics reporting 1988 results than had reported for 1987. In addition, more than twice as many clinics reported via RecordKeeper than in 1987. Of the 22,649 stimulation cycles, 16,636 (73%) were reported via the paper data forms and the remainder on disks created with RecordKeeper. The treatments and the results for IVF-ET cycles initiated in 1988 are presented either (1) as summary statistics using the pooled results from both data forms and floppy disks, (2) or as more detailed analyses using the individual patient records submitted via disks only. Unless stated otherwise, each analysis is based on the pooled resul~s combining both paper form and disk information.
RESULTS In 1988, the 135 clinics initiated 22,649 stimulation cycles in 16,195 women. Seventy-eight percent (17,753) of the cycles resulted in an oocyte retrieval. Of the 135 clinics, 126 (93%) reported at least one live delivery. The IVF-ET treatments described below resulted in 3,508 clinical pregnancies and 2,627 live deliveries. There were 3,427 babies born, including 580 sets of twins, 100 triplets, 11 quadruplets, and 3 quintuplets. For babies whose sex was known, the male:female ratio was 1,635:1,534 or 1.06. (There were 59 clinical pregnancies with unknown outcome as of October 31, 1989.) Hyperstimulation with negative beta-human chorionic gonadotropin ({3-hCG) was reported in 25 (0.1%) stimulation cycles and with positive {3-hCG in30 (0.1%). In Vitro Fertilization
In 1988 each of the 135 clinics reported performing IVF. The clinics reported 13,647 IVF retrievals, of which 1,801 (13%) were by laparoscopy, 11,678 (86%) by ultrasound, 164 (1%) by a combination of laparoscopy and ultrasound, and 4 by laparotomy. Table 1 provides the distributions of selected outcomes by number of IVF retrievals. The maximum number of retrievals reported by a clinic was 964. A total of 2,243 clinical pregnancies (de14
MRI and AFS IVF-ET in the U.S. during 1988
fined by rising {3-hCG and the presence of gestational sac(s) on ultrasound) were conceived through IVF. An ET resulted from 11,821 (87%) of retrievals. The maximum number ofETs performed by a single clinic was 888. The overall clinical pregnancy and delivery rates per· ET were 19% and 14%, respectively. The clinical pregnancy rates by number of transfer cycles were 20% (70/342) for <25 cycles, 18% (617 /3504) for 25 to 99 cycles, 19% (621/3229) for 100 to 199 cycles, and 20% (935/4746) for 200 or more cycles. The corresponding delivery rates were 14%, 13%, 14%, and 14%, respectively. Three clinics each had more than 100 clinical pregnancies and accounted for 507 (23%) of all clinical pregnancies. Seventy (52%) of the clinics reported <10 pregnancies, while overall124 (92%) clinics reported at least one clinical pregnancy usingiVF. Of the clinical pregnancies, 1,657 (74%) resulted in a live delivery, of which 13% were reported to be preterm. The Registry defines deliveries (preterm as live births occurring before 36 weeks gestation, and term as live births occurring thereafter) in the reporting year in which conception occurred. (As of October 31, 1989, the outcomes of 43 pregnancies were still unknown.) Among the 16 clinics not reporting a delivery, the maximum number of retrievals was 28. Three clinics accounted for 23% of the deliveries as aresult ofiVF. Also, 38 (28%), 62 (46%), and 19 (14%) of the clinics had delivery rates (per retrieval) between 1% and 9%, 10% to 19%, and 20% to 36%, respectively. The clinic reporting the maximum delivery rate (36%) performed 14 retrievals. There were 2,133 babies born including 919 resulting from 421 multiple births. Overall, 19% of the clinical pregnancies resulted in a multiple delivery: 356 twin, 55 triplet, 8 quadruplet, and 2 quintuplet deliveries. In addition to the 532 reported (spontaneous) abortions given in Table 1, there were 20 stillbirths and 15 therapeutic abortions recorded. The Registry defines a (spontaneous) abortion as a clinical pregnancy loss occurring before a gestational age of 20 weeks and a stillbirth as the birth of a nonviable fetus of 20 weeks gestation or more. The clinical pregnancy and delivery rates increased with the average number of embryos transferred per cycle. The clinical pregnancy and delivery rates ranged from 16% and 12% for an average of <3 embryos transferred to 22% and 16% for 4 or more embryos transferred, respectively. In addition, the rate of multiple deliveries increased from Fertility and Sterility
Table 1
IVF Treatment Outcome by Total Number of Retrieval Cycles
IVF cycles
No. of clinics
No. of retrievals
<25 25 to 99 100 to 199 >199
32 59 30 14
339 3,310 4,077 5,921
135
13,647
Total
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies'
(19) (15) (17) (17)
18 (29) 116 (23) 148 (22) 250 (25)
2 (3) 30 (6) 36 (5) 48 (5)
2,243 (16)
532 (24)
116 (5)
63 500 686 994
No. of all deliveries d 43 383 511 720
(13) (12) (13) (12)
1,657 (12)
" Clinical pregnancy rates are expressed in parentheses as a percent of retrievals. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies.
' Ectopic pregnancy rates are expressed in parentheses as a percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of retrievals.
2.8% to 4.3%, respectively. Only 3 clinics reported transferring on average more than 5 embryos per cycle, with a maximum of 5.3 An analysis of the 2,623 ET cycles recorded through RecordKeeper by 50 clinics also indicated that the clinical pregnancy rate increased with the number of embryos transferred. The clinical pregnancy rate ranged from 4% (12/332) for 1 embryo transferred to 22% (132/609) for 5 or more embryos transferred per cycle. In addition, the rates of multiple deliveries varied with the number of embryos transferred-from 0.3% (2/749) for 2 or fewer embryos transferred to 5.4% (33/609) for 5 or more embryos transferred. Fifty-six (41%) clinics reported administering a gonadotropin-releasing hormone (GnRH) analog as part of their most commonly used stimulation regimens. In addition, the outcomes of 2,623 ET cycles reported via RecordKeeper were also evaluated according to stimulation protocol (Table 2). The most frequently used stimulation regimen was human menopausal gonadotropin (hMG) with clo-
miphene citrate, followed by hMG alone, and hMG and a GnRH analog. The pregnancy and delivery rates, 21% and 15% respectively, were highest for the protocol including the combination hMG, follicle-stimulating hormone (FSH), and a GnRH analog. Table 3 shows the outcomes of the above 2,623 ET cycles by age of the woman receiving treatment. The clinical pregnancy and delivery rates declined steadily with age. In women 45 years or older there were 7 ET cycles resulting in 1 clinical pregnancy, which ended in a spontaneous abortion. Table 4 presents cancellation, clinical pregnancy, and delivery rates for IVF and GIFT by selected diagnoses for cycles submitted through RecordKeeper. The cancellation rate was highest for women with unexplained infertility and lowest for those with tubal disease. For IVF, the clinical pregnancy and delivery rates were highest for couples with male immune problems. Sixteen chromosomal abnormalities were reported. These included 1 trisomy 13, 2 trisomy 16,
Table2
Outcome by Stimulation Protocol and Procedure IVF
Stimulation protocol
No. of cycles
No. of canceled cycles"
No. of ETcycles
GIFT
No. of clinical pregnancies b
No. of multiple deliveries'
No. of transfer cycles
No. of clinical pregnancies d
No. of multiple deliveries e
(31) (18) (32) (33)
554 479 559 364
100 (18) 81 (17) 63 (11) 47 (13)
19 (3.4) 24. (5.0) 10 (1.8) 6 (1.6)
149 240 122 143
915 527
207 (23) 181 (34)
476 191
101 (21) 30 (16)
14 (2.9) 7 (3.7)
77 62
21 (27) 13 (21)
7 (9.1) 6 (9.7)
6,013
1,690 (28)
2,623
422 (16)
80 (3.1)
793
215 (27)
57 (7.2)
HMGalone HMG, GnRH analog HMG, clomiphene HMG,FSH HMG, FSH, GnRH analog Other combinations
1,217 1,061 1,275 1,018
Total
374 193 404 331
a A cycle is defined as canceled if no retrieval is performed. Values in parentheses are expressed as percent. b Clinical pregnancy rates are expressed in parentheses as a percent of ET cycles. 'Multiple delivery rates are expressed in parentheses as a
Vol. 53, No.1, January 1990
55 53 28 45
(37) (22) (23) (31)
13 14 7 10
(8.7) (5.8) (5.7) (7.0)
percent of ET cycles. d Clinical pregnancy rates are expressed in parentheses as a percent of G 1FT transfer cycles. e Multiple delivery rates are expressed in parentheses as a percent of G 1FT transfer cycles.
MRI and AFS
IVF-ET in the U.S. during 1988
15
TableS
In Vitro Fertilization Treatment Outcome by Woman's Age No. of ETcycles
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnanciesc
No. of all deliveries d
<25 25to 29 30to34 35to 39 40+ Unknown
25 397 1,091 904 198 8
10 (40) 75 (19) 181 (17) 135 (15) 20 (10) 1 (13)
0 (0) 24 (32) 39 (22) 32 (24) 12 (60) 0 (0)
1 (9) 5 (6) 7 (4) 5 (4) 1 (5) 0 (0)
10 (40) 53 (13) 147 (13) 99 (11) 8 (4) 1 (13)
45 (4.1) 17 (1.9) 4 (2.0) 0 (0)
Total
2,623
422 (16)
107 (25)
19 (4)
318 (12)
80 (3.0)
Age
No. of multiple deliveries e
y
3 (12.0) 11 (2.8)
a Clinical pregnancy rates are expressed in parentheses as a percent of ET cycles. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies. c Ectopic pregnancy rates are expressed in parentheses as a
percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of ET cycles. e Multiple delivery rates are expressed in parentheses as a percent of ET cycles.
1 trisomy 18, 4 trisomy 21, and 1 trisomy 22; there were also 1 triploid, 3 tetraploid, 1 Mosaic 45-46 and 1 XYY syndrome (twins), and 1 Tetralogy of Fallot in a twin delivery. Except for one trisomy 21, these resulted in either a spontaneous or therapeutic abortion. There were 23 different reported congenital malformations in 18 pregnancy outcomes. These included 7 reported outcomes with 9 central nervous system (CNS) malformations (spina bifida and hydrocephalus (2) terminated in therapeutic abortion, hydrocephalus, microcephalus, corpus callosum, Klippel-Feil syndrome, cranial synostosis terminated in spontaneous abortion), 2 outcomes with 3 cardiovascular malformations (aortic stenosis and ventricle septal defect, hydroplastic left
ventricle defect), 5 outcomes with 6 gastrointestinal malformations (tracheal-esophageal fistula and renal atresia, tracheal-esophageal fistula (2), tracheal fistula, imperforate anus), 1 genitourinary (unilateral hydronephrosis), 2 respiratory tract (cleft palate (2)), 1 musculoskeletal (clubfoot), 2 eye (coloboma in twins), and 1 skin (hemangiomaunspecified). The known maternal ages ranged from 24 to 39 years. Except for the 3 outcomes cited above, these pregnancies resulted in liveborn outcomes.
Table 4
Gamete Intrafallopian Transfer
There were 101 clinics that performed GIFT alone (i.e., not in conjunction with IVF) in 3,080
Outcome by Infertility Diagnosis and Treatment IVF
Infertility diagnosis a Tubal disease/ problem 6 Female unexplained Female immune Endometriosis Male unexplained Male immune Male sperm abnormalities h
No. of stimulation cycles
No. of canceled cyclesb
No. of embryo transfers
No. of clinical pregnanciesc
No. of all deliveriesd
No. of transfer cycles
No. of clinical pregnancies•
No. of all deliveries'
3,102 642 237 2,021 291 207
979 (32) 345 (54) 82 (35) 997 (49) 124 (43) 68 (33)
1,803 172 116 682 107 103
282 (16) 24 (14) 15 (13) 104 (15) 10 (9) 26 (25)
211 (12) 17 (10) 11 (9) 75 (11) 8 (7) 20 (19)
104 180 33 386 62 31
15 (14) 43 (24) 11 (33) 103 (27) 16 (26) 7 (23)
13 (12) 43 (24) 9 (27) 80 (21) 14 (23) 6 (19)
1,287.
525 (41)
496
78 (16)
55 (11)
188
46 (24)
38 (20)
a Represents cycle with specific diagnosis indicated. Patient may be represented in more than one category. b A cycle is defined as canceled if no retrieval is performed. Values in parentheses are expressed as percent. c Clinical pregnancy rates are expressed in parentheses as a percent of ET cycles. d Delivery rates (live) are expressed in parentheses as a percent of ET cycles.
16
MRI and AFS
GIFT
IVF-ET in the U.S. during 1988
e Clinical pregnancy rates are expressed in parentheses as a percent of G 1FT transfer cycles. f Delivery rates (live) are expressed in parentheses as percent of G 1FT transfer cycles. 6 Tubal disease or problem including previous tubal surgery, tubal ligation, absence oftube(s). h Includes oligospermia, asthenospermia, and teratospermia.
Fertility and Sterility
Table 5
Gamete Intrafallopian Transfer Outcome by Total Number of GIFT Retrievals Performed
GIFT cycles
No. of clinics
No. of GIFT retrievals
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies'
No. of all deliveries d
<25 25 to 99 >99
65 29 7
416 1,336 1,328
88 (21) 390 (29) 368 (28)
17 (19) 80 (21) 74 (20)
0 (0) 21 (5) 21 (5)
71 (17) 302 (23) 281 (21)
101
3,080
846 (27)
171 (20)
42 (5)
654 (21)
Total
a Clinical pregnancy rates are expressed in parentheses as a percent of retrievals. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies.
' Ectopic pregnancy rates are expressed in parentheses as a percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of retrievals.
retrieval cycles. Table 5 gives the treatment results by number of GIFT retrieval cycles. Of the clinics performing GIFT, 30 (30%) did not report a delivery. However, in this group the maximum number of retrievals performed was 13, and 29 of the clinics performed <10 retrievals. Excluding clinics with <10 retrievals, the maximum reported delivery rate was 43%. Two clinics reported >200 GIFT treatments. There were 846 (27%) GIFT cycles that resulted in a clinical pregnancy. Seventy-six (75%) clinics had at least one clinical pregnancy, and of these, 54 (71%) had <10 pregnancies. There were 5 clinics that had 40 or more pregnancies, accounting for 316 (37%) of the total reported. The spontaneous abortion rate associated with GIFT was 20%. Fifteen stillbirths were also recorded. Four clinics accounted for 218 (33%) of the 654 deliveries. There were 892 babies delivered, including 159 sets of twins, 34 triplets, 3 quadruplets, and 1 quintuplet. In addition, there were 98 (15%) preterm deliveries. (There were 9 clinical pregnancies whose outcomes were unknown as of October 31, 1989). Table 6 presents outcomes of the GIFT procedure by age of the patient using RecordKeeper data. Clinical pregnancy and delivery rates decreased with the age of the woman. Of the 148 cycles in women <30 years of age, 13 were in women <25, and resulted in 4 deliveries. Also, there were 10 cycles in women 45 years or older, none of which resulted in a clinical pregnancy. Table 2 presents the outcomes of 793 GIFT transfer cycles according to stimulation protocol. The pregnancy and delivery rates, 37% and 31%, respectively, were highest for the protocol including hMG alone. Table 4 presents the outcome of GIFT by infertility diagnosis. The highest rates of clinical pregnancy and delivery were in women with immune
problems. The lowest rates were in women with tubal problems. Nine chromosomal abnormalities were reported. These included 1 trisomy 13, 2 trisomy 15, 2 trisomy 18, 3 trisomy 21, 1 XYY syndrome, and 1 Turner syndrome. The Turner syndrome resulted in a spontaneous abortion, and all others in therapeutic abortions. There were six reported congenital malformations in four pregnancy outcomes. These included one stillborn with anencephaly, one kidney (unspecified) in a liveborn, one congenital heartblock in a liveborn, and one stillborn with multiple malformations (spina bifida, clubfoot, and hypospadias).
Vol. 53, No.1, January 1990
GIFT In Combination With IVF
Fifty-nine (44%) of the 135 clinics reported using GIFT in combination with IVF. There were 671 oocyte retrievals of which 171 (25%) resulted in a clinical pregnancy and 136 (20%) in a delivery. Five of the clinics performed 326 (49%) of the combined procedures. Of the 671 retrievals, 577 (86%) were performed using laparoscopy. The 136 deliveries resulted in 172live babies, including 27 sets of twins, and 5 triplets. In addition, there was a 13% preterm delivery rate. (As of October 31, 1989, there were 3 pregnancies whose outcomes were unknown to the Registry.) There was one outcome with a reported congenital malformation: anencephaly resulting in a therapeutic abortion. Zygote Intrafallopian Transfer (ZIFT) and Related Procedures
Twenty clinics performed 385 stimulation cycles using ZIFT or a similar procedure (i.e., pronuclear stage tubal transfer (PROST), tubal embryo transfer (TET), tubal pre-embryo transfer (TPET), collectively referred to as ZIFT). Of these cycles, 355 MRI and AFS
IVF-ET in the U.S. during 1988
17
TableS
Gamete lntrafallopian Transfer Treatment Outcome by Woman's Age No. of GIFT cycles
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies •
No. of all deliveries d
No. of multiple deliveries e
<30 30to 34 35to 39 40+ Unknown
148 327 222 92 4
52 (35) 96 (29) 51 (23) 13 (14) 3 (75)
7 (13) 13 (14) 15 (29) 5 (38) 2 (67)
2 (4) 6 (6) 2 (4) 0 (O) 0 (0)
46 (31) 83 (25) 37 (17) 8 (9) 1 (25)
14 (9.5) 31 (9.5) 10 (4.5) 2 (2.2) 0 (0)
Total
793
215 (27)
42 (20)
10 (4)
175 (22)
57 (7.2)
Age y
• Clinical pregnancy rates are expressed in parentheses as a percent of G 1FT cycles. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies. • Ectopic pregnancy rates are expressed in parentheses as a
percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of G1FT cycles. • Multiple delivery rates are expressed in parentheses as a percent of G 1FT cycles.
(92%) resulted in an oocyte retrieval, and 275 (71%) in a transfer cycle. Six of the clinics performed 20 or more retrievals for ZIFT. Of the 355 retrievals, 97 (27%) resulted in a clinical pregnancy and 71 (20%) in a delivery. Of the 71 deliveries, 3 (4%) were preterm. Ninety-eight live babies, including 19 sets of twins and 4 triplets, were delivered. (As of October 31, 1989, there was 1 pregnancy whose outcome was unknown to the Registry.) There were no reported chromosomal abnormalities or congenital anomalies for ZIFT.
were unknown to the Registry.) In addition, there were 2,4 74 patients whose IVF cycles resulted in freezing 9,605 embryos, or 3.9 per patient. There was one liveborn with aortic atresia and other reported anomalies.
Frozen Embryo Transfers
There were 1,025 frozen ET cycles performed in 67 clinics. Four of the clinics performed 50 or more such cycles, with a reported maximum of 103 transfer cycles. These four clinics accounted for 48% of the clinical pregnancies, and 49% of the deliveries. Twenty-eight (42%) of the clinics had at least 1 clinical pregnancy. Table 7 details the distribution of selected outcomes by number of frozen embryo transfer cycles. Included in the 73 deliveries were 7 sets of twins and 1 set of triplets. (As of October 31, 1989, there were 2 pregnancies whose outcomes Table 7
In 1988, 26 clinics reported performing IVF-ET with donated oocytes. There were 130 patients who underwent 158 donor transfers. Fifty-one (32%) of the donor transfers produced a clinical pregnancy. Thirty-six (23%) live deliveries resulted, including 12 sets of twins and 1 set oftriplets. (As of October 31, 1989 there was 1 pregnancy whose outcome was unknown.) There were no reported chromosomal abnormalities or congenital anomalies with this procedure. DISCUSSION
This report summarizes the IVF-ET results of 135 IVF Registry clinics in the U.S. There was a 41% increase over 1987 in clinics reporting their data to the Registry. In addition more than twice
Treatment Outcome by Number of Frozen Embryo Transfer Cycles
Frozen embryo transfer cycles
No. of clinics
<25 25to49 50+
54 9 4
Total
67
No. of clinical pregnancies a
No. of abortionsb
No. of ectopic pregnancies•
No. of all deliveries d
396 307 322
25 (6) 26 (8) 50 (15)
4 (16) 7 (27) 12 (24)
1 (4) 2 (7) 2 (4)
18 (5) 19 (6) 36 (11)
1,025
101 (10)
23 (23)
5 (5)
73 (7)
No. of transfer cycles
a Clinical pregnancy rates are expressed in parentheses as a percent of transfer cycles. b Spontaneous abortion rates are expressed in parentheses as a percent of clinical pregnancies.
18
IVF of Donated Oocytes
MRI and AFS
IVF-ET in the U.S. during 1988
• Ectopic pregnancy rates are expressed in parentheses as a percent of all pregnancies (clinical and ectopic). d Delivery rates (live) are expressed in parentheses as a percent of transfer cycles.
Fertility and Sterility
as many clinics reported their results via RecordKeeper. Although there were changes in the practice of IVF-ET, there is a reassuring consistency between the 1987 and 1988 data received by the Registry. In 1988 the number of stimulation cycles reported increased by 55% over 1987. In addition, the percent of retrieval cycles for the combination IVF and GIFT procedure doubled over that reported in the last year. Also, the ZIFT procedure was reported to the Registry for the first time this year by a number of clinics. There was a marked increase in the percent of retrievals for IVF that were performed by ultrasound. In 1987, 57% of retrievals were by ultrasound, whereas in 1988, 86% were by ultrasound. The clinical pregnancy rate per retrieval for IVF remained at 16%, as it was in 1987. For GIFT the pregnancy rate increased slightly from 25% to 27%. The rates of multiple birth were similar to the previous year's: 3.1% for IVF and 6.4% for G 1FT, compared with 2.7% and 5.2% for 1987. There were more than twice as many frozen ET cycles as reported in 1987. The clinical pregnancy rate was 10% for both years. In this report outcomes of IVF and G 1FT treatment by infertility diagnosis were presented. The numbers in some categories were somewhat small, because these data were not recorded by all clinics using RecordKeeper. Therefore, the numbers do not necessarily reflect all subjects with a particular diagnosis. However, these results do provide important information. It is expected that as the Registry's database grows, additional characteristics of IVF and G 1FT practices will be described in future reports. With three years' worth of data, the Registry can now provide a resource for examining trends in numerous areas, including stimulation protocols, retrieval methods, hyperstimulation rates, and occurrence of birth outcomes including congenital malformations and chromosomal abnormalities. Acknowledgments. Medical Research International would like to express its appreciation to the staffs at the IVF /ET clinics for their critical support of The IVF Registry. The clinics located at the following facilities contributed data as of October 1, 1989: Alabama-ART Program at Birmingham, Birmingham; University of Alabama, Birmingham; Arizona-Arizona Fertility Institute, Phoenix; Southwest Fertility Center, Phoenix; California-Alta Bates Hospital, Berkeley; Beverly HillsEncino Fertility Institutes, Encino; UCI-AMI Center for Reproductive Health, Garden Grove; Scripps Clinic Fertility Center, La Jolla; Lorna Linda University, Lorna Linda; Long Beach Memorial Hospital/University of California at Irvine, Long Beach; The Center for Reproductive Medicine at Cedars-Sinai Medical Center, Los Angeles; University of California at Los Vol. 53, No.1, January 1990
Angeles; Institute for Reproductive Research/The Hospital of the Good Samaritan, Los Angeles; Century City Hospital, Los Angeles; USC School of Medicine, Los Angeles; Hoag Fertility Service Center, Newport Beach; Northridge Hospital, Northridge; AMI South Bay Hospital, Redondo Beach; IGO Medical Group of San Diego; Children's Hospital, San Diego; University of California at San Francisco; Pacific Fertility Center, San Francisco; Fertility and Reproductive Health Institute of Northern California, San Jose; Forest Fertility Center, San Jose; Nova Fertility Center, San Mateo; John Muir Hospital, Walnut Creek; Whittier Hospital Medical Center, Whittier; Colorado-Reproductive Genetics In Vitro, P.C., Denver; Infertility, Gynecology and Obstetric Associates, Englewood; Connecticut-Mount Sinai Hospital, Hartford; Yale University School of Medicine, New Haven; Delaware-Medical Center of Delaware at Christiana Hospital, Newark; FloridaShands Hospital, Gainesville; Fertility Institute of Northwest Florida, Gulf Breeze; Memorial Medical Center, Jacksonville; Northwest Center for Infertility and Reproductive Endocrinology, Margate; Sand Lake Hospital IVF Center/Dr. G. W. DeVane, Orlando; Humana Women's Hospital, Tampa; Georgia-Reproductive Biology Associates, Atlanta; Augusta Reproductive Biology Associates, Augusta; Medical College of Georgia, Augusta; Iowa-McFarland Clinic, Ames; University of Iowa Hospitals and Clinics, Iowa City; Illinois-Fertility Center, Chicago; IVF Illinois, Chicago; Mount Sinai Hospital Medical Center, Chicago; Glenbrook Hospital, Glenview; Indiana-Indiana University Hospital, Indianapolis; Pregnancy Initiation Center, Indianapolis; Methodist Hospital, Indianapolis; Kansas-Reproductive Resource Center of Greater Kansas City, Overland Park; Center for Reproductive Medicine, Wichita; Kentucky-The Fertility Institute (Ohio and Kentucky), Fort Thomas; University of Kentucky, Lexington; Norton Hospital, Louisville; Louisiana-Fertility Center of Louisiana, Kenner; Fertility Institute of New Orleans; MarylandThe Johns Hopkins University School of Medicine, Baltimore; University of Maryland, Baltimore; Women's Hospital Fertility Center at Greater Baltimore Medical Center, Baltimore; Montgomery Infertility Institute, Bethesda; Massachusetts-Beth Israel Hospital, Boston; Brigham and Women's Hospital, Boston; Boston IVF, Brookline; Michigan-Center for Reproductive Medicine at Oakwood Hospital, Dearborn; Hutzel Hospital/Wayne State University, Detroit; Blodgett Memorial Medical Center, Grand Rapids; William Beaumont Hospital, Royal Oak; Saginaw General Hospital, Saginaw; Ann Arbor Reproductive Medicine Associates, Ypsilanti; Minnesota-University of Minnesota, Minneapolis; Missouri-International Center for Reproductive Research, Kansas City; Jewish Hospital of St. Louis, St. Louis; Mississippi-University of Mississippi, Jackson; Nebraska-Nebraska Methodist Hospital, Omaha; Nevada-Northern Nevada Fertility Center, Reno; New Hampshire-Dartmouth Hitchcock Medical Center, Hanover; New Jersey-UMDNJ at Newark, Newark; New Mexico-Presbyterian Hospital, Albuquerque; New YorkFertility and Hormone Center/ Albert Einstein College of Medicine, Dobbs Ferry; Columbia Presbyterian Medical Center, New York City; Cornell University Medical Center, New York City; Mount Sinai Medical Center, New York City; IVF Australia Prggram/United Hospital, Port Chester; Long Island IVF, Port·Jefferson; Institute for Reproductive Health and Infertility, Rochester; University of Rochester, Rochester; SUNY Health Science Center/Crouse Irving Memorial Hospital, Syracuse; North Carolina-University of North Carolina School of Medicine, Chapel Hill; Center for Reproductive Medicine, MRI and AFS
IVF-ET in the U.S. during 1988
19
Charlotte; Duke University Medical Center, Durham; North Dakota-Centennial Medi.:al Center, Minot; Ohio-Akron City Hospital, Akron; Bethesda Fertility Center, Cincinnati; Cleveland Clinic Foundation, Cleveland; Midwest Reproductive Institute, Columbus; Ohio State University, Columbus; Miami Valley Hospital Fertility Center, Dayton; OklahomaBennett Fertility Institute, Oklahoma City; Hillcrest Fertility Center, Tulsa; Oregon-Oregon Health Science Center, Portland; Pennsylvania-St. Luke's Hospital, Bethlehem; Christian Fertility Institute, Easton; Endocrine Histology Associates, Melrose Park; Albert Einstein, North Division, Philadelphia; Hospital of the University of Pennsylvania, Philadelphia; Pennsylvania Reproductive Associates at Pennsylvania Hospital, Philadelphia; Magee-Women's Hospital, Pittsburgh; Shadyside Hospital, Pittsburgh; Women's Clinic Limited, W. Reading; Rhode Island-Women and Infants' Hospital, Providence; South Carolina-Medical University of South Carolina, Charleston; Southeastern Fertility Center, Mt. Pleasant; Tennessee-Humana East Ridge Hospital, Chattanooga; University of Tennessee, Knoxville; Vanderbilt University Medical Center, Nashville; Texas-St. David's Community Hospital, Austin; Trinity IVF/ET, Carrollton; University of Texas Southwestern Medical Center, Dallas; Fort Worth Infertility Center, Fort Worth; Baylor IVF Program, Houston; University of Texas Medical School, Houston; Fertility Program at Methodist Hospital, San Antonio; Utah-University of Utah, Salt Lake City; Virginia-Genetics & IVF Institute, Fairfax; The Howard and Georgeanna Jones Institute for Reproductive Medicine, Norfolk; Henrico Doctors' Hospital IVF/GIFT Program, Richmond; Medical College of Virginia, Richmond; Washington-Swedish Hospital Medical Center, Seattle; University of Washington, Seattle; Washington, D.C.-Columbia Hospital for Women Medical Center; George Washington University Medical Center; Wisconsin-Appleton Medical Center, Appleton; University of Wisconsin Clinics, Madison; Advanced Institute of Fertility, Milwaukee; Medical College of Wisconsin, Milwaukee. REFERENCES 1. U.S. Congress, Office of Technology Assessment: Infertil-
2.
3. 4.
5.
ity: Medical and Social Choices. OTA-BA-358, Washington, D.C., U.S. Government Printing Office, May, 1988 Subcommittee on Regulation, Business Opportunities, and Energy, Committee on Small Business, House of Representatives: Consumer Protection Issues Involving In Vitro Fertilization Clinics. Serial No. 101-05, Washington, D.C., U.S. Government Printing Office, March, 1989 DeCherney AH, Hartz SC: Assisted reproduction: registration vis-a-vis regulation. Fertil Steril 51:68, 1989 Medical ReRearch International, The American Fertility Society Special Interest Group: In vitro fertilization/embryo transfer in the United States: 1985 and 1986 results from the National IVF-ET Registry. Fertil Steril 49:212, 1988 Medical Research International, The American Fertility Society Special Interest Group: In vitro fertilization/embryo transfer in the United States: 1987 results from the National IVF-ET Registry. Fertil Steril51:13, 1989
Laboratories, the American Fertility Society and SART. Once again, this report from MRI has demonstrated the dramatic increase in the number and types of Assisted Reproductive Technology (ART) treatments performed in the United States. The initial report from the Registry, covering the years 1985 and 1986, detailed 5,253 IVF cycles for the 2 years that resulted in a total of 568 babies born: In 1987 there were 14,647 IVF cycles that resulted in 1,858 babies. The present report covering 1988 includes 22,649 IVF stimulation cycles with 3,427 babies born. Both prior reports included IVF, GIFT, frozen ETs and pregnancies using donated oocytes. The 1988 report now includes also ZIFT and related procedures. Even more impressive is the increase in the number of IVF Clinics in the United States that are voluntarily contributing their data to the Registry. In 1985 there were 30 reporting clinics; in 1986 there were 41 reporting clinics; in 1987 there were 96 reporting clinics and 1988 includes data from 135 member clinics. Most importantly, the 1988 Registry data demonstrated that 93% of the United States IVF clinics produced at least one live-born child in 1988, thus soundly refuting the claims made previously that over half the United States IVF programs have failed to produce a single successful pregnancy. In 1989 a Congressional Subcommittee hearing was held at which the results of a questionnaire survey of U.S. IVF and GIFT clinics were presented. The statistical methodology used for that report was criticized on a number of grounds. This report from the Registry provides data that is statistically more valid in that there are equal reporting periods for all programs, deliveries are counted for the year in which the treatment was initiated, and data are given only for pregnancies in which the outcome is known. The Congressional Subcommittee report, however, did provide clinic-specific statistics that had not previously been available. The statistical group at MRI is to be commended on their meticulous and painstaking collection, analysis and reporting of the annual data on the United States ART treatments. Hopefully in the future the Registry will serve the dual purpose of providing scientific analysis as well as clinic-specific results.
COMMENT
This paper is the third report from the United States IVF Registry, a joint project of MRI, Serono
20
MRI and AFS
IVF-ET in the U.S. during 1988
Martin M. Quigley, M.D. President, SART
Fertility and Sterility