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Assisted reproductive techniques in Latin America: the Latin American Registry, 2013

Reproductive BioMedicine Online, Volume 32, Issue 6, June 2016, Pages 614–625

Abstract

Multinational data on assisted reproduction techniques undertaken in 2013 were collected from 158 institutions in 15 Latin American countries. Individualized cycle-based data included 57,456 initiated cycles. Treatments included autologous IVF and intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations. In autologous reproduction, 29.22% of women were younger than 35 years, 40.1% were 35–39 years and 30.6% were 40 years or older. Overall delivery rate per oocyte retrieval was 20.6% for ICSI and 25.4% for IVF. Multiple births included 20.7% for twins and 1.1% for triplets and over. In oocyte donations, twins reached 30% and triplets 1.4%. In singletons, pre-term births were 7.5%: 36.58% in twins and 65.52% in triplets. The relative risk for prematurity was 4.9 (95% CI 4.5 to 5.3) in twins and 8.7 (95% CI 7.6 to 10.0) in triplets and above. Perinatal mortality was 29.4 per 1000 in singletons, 39.9 per 1000 in twins and 71.6 per 1000 in high order multiples. Elective single embryo transfer represented only 2% of cycles, with delivery rate of 39.1% in women aged 34 years or less. Given the effect of multiple births and prematurity, it is mandatory to reduce the number of embryos transferred in the region.

Keywords: assisted reproductive technology, epidemiology, IVF/ICSI, Latin America, perinatal outcome, registry.

Introduction

The Latin American Registry of Assisted Reproduction (RLA) was established in 1990, as the first multinational and regional registry collecting data on assisted reproduction techniques. For the first 20 years, summary data were obtained electronically via a web page from every participating institution, belonging to 12 countries in the region. Since 2010, new software has been developed and implemented, which allows for the collection of cycle-based data from every treatment cycle. Data collection is therefore recorded individually, starting with ovarian stimulation until birth or spontaneous abortion.

Today, individualized data are obtained from assisted reproducton technique treatments carried out in 158 institutions in 15 countries, covering more than 80% of assisted reproduction technique cycles carried out in the region. This report corresponds to the 25th edition of RLA. Previous reports, from 1990 to 1998, are available as printed copies; and from 1999 to 2009 as PDF files, which can be downloaded from the web page of the Latin American Network of Assisted Reproduction (REDLARA) at: http://www.redlara.com. Today, reports are published simultaneously in RBM Online, and in the JBRA Assisted Reproduction, the official journal of REDLARA.

The main objectives of RLA are to disseminate information on assisted reproduction technique procedures carried out in Latin America; monitor outcomes, as well as trends in safety and efficacy among centres and countries; empower infertile couples in their capacity to evaluate risks and benefits when requesting assisted reproduction technique treatments; and develop a robust database for epidemiological studies.

In this report, we report information on availability, effectiveness and perinatal outcomes of assisted reproduction technique treatment started between 1 January 2013 and 31 December 2013, and babies born up to September 2014. It is also our aim to describe regional trends on how assisted reproduction techniques are practised in the region, including the number of embryos transferred, multiple births and its effect on pre-term births and perinatal mortality.

Material and methods

Data on assisted reproduction techniques were collected from 158 centres in 15 countries (Table S1), covering IVF, intracytoplasmic sperm injection (ICSI), oocyte donation (both fresh and frozen), frozen embryo transfer, and preimplantation genetic diagnosis (PGD) and screening, registered together as PGD. In addition to assisted reproduction tehcnhiques, data on intrauterine insemination (IUI) using husband and donor semen were also included. This report includes treatments started between 1 January 2013 and 31 December 2013, and babies born up to September 2014. As part of the accreditation programme, all participating institutions agree to have their data registered and published by the Latin American Registry of Assisted Reproduction. Given it is a multinational registry, no other consent form was requested.

As was the case in the previous 2 years, data were collected using an individualized cycle-based software. The method of collecting and reporting data is also similar to that used in the previous 2 years, making all tables comparable (Zegers-Hochschild et al., 2015).

Each centre entered their data directly onto an online RLA web-based system. Built-in algorithms for internal consistency (any error or discrepancy not identified by the software) was discussed and clarified by RLA's central office. Given that the RLA is a voluntary multinational registry, centres are not obliged to upload each case immediately as the cycle is initiated. Therefore, some cases are sent to the RLA upon recruitment whereas others are included retrospectively.

As the new cycle-based registry has only been available for 2 years, the calculation of cumulative delivery rates could not be made directly. Therefore, we made estimates by adding deliveries derived from fresh and frozen transfers in every age group.

When appropriate, the chi-squared test was used to analyse independence of categorical variables. P < 0.05 was considered statistically significant. Relative risks are presented with the corresponding 95% confidence interval. All terminologies used in this registry correspond to the glossary published in 2009 by the International Committee for Monitoring Assisted Reproductive Technologies and the World Health Organization (Zegers-Hochschild et al., 2009). Cases of severe ovarian hyperstimulation syndrome, requiring hospitalization or medical interventions, were registered.

Results

Participating centres

One hundred and fifty-eight centres in 15 countries reported assisted reproduction technique procedures carried out during 2013. They included 36,494 initiated autologous fresh IVF–ICSI cycles; 10,912 frozen embroy transfers; 8434 oocyte donation (heterologous) cycles, of which, 5927 were fresh transfers and 2507 frozen embryo transfers; and 1616 initiated cycles for fertility preservation.

Access to assisted preproduction technique procedures, defined as the sum of IVF–ICSI initiated cycles, frozen embroy transer and oocyte donation cycles, per million women aged 15–45 years, reached a mean of 425 with large variation between countries (Table 1).

Table 1 Assisted reproduction technique procedures and access in 2013.

Country Number of clinics Assisted reproductive techniques Totald Accesse
IVF–ICSIa IVFb ICSIb FET Oocyte donation Oocyte donation (FET) Fertility preservationc
Argentina 27 7769 749 6255 2481 1655 815 396 12,720 1368
Bolivia 2 280 195 71 17 46 3 840 346 141
Brazil 56 17,042 1060 14,974 5833 1159 579 0 24,613 512
Chile 8 1646 130 1405 543 170 84 61 2443 634
Colombia 9 967 288 613 182 209 95 5 1453 136
Ecuador 6 654 206 391 159 208 72 145 1093 297
Guatemala 1 99 52 47 16 20 1 9 136 39
Mexico 28 4476 1494 2648 929 1421 378 31 7204 251
Nicaragua 1 100 29 67 0 10 0 0 110 72
Panama 2 408 0 362 83 56 17 5 564 710
Paraguay 1 37 9 22 2 0 0 2 39 24
Peru 6 1404 470 837 390 587 306 98 2687 367
Dominican R. 1 49 18 30 6 36 2 0 93 40
Uruguay 2 340 35 239 52 56 19 5 467 652
Venezuela 8 1223 438 638 219 294 136 19 1872 274
Total 158 36,494 5173 28,599 10,912 5927 2507 1616 55,840 425

a Initiated cycles.

b Oocyte retrieval with one or more mature oocytes.

c Initiated fertility preservation cycles.

d Excludes fertility presevation.

e Number of cycles per million of women aged 15–45 years.

FET, frozen embryo transfer; ICSI, intracytoplasmic sperm injection.

Size of participating institutions

Excluding fertility preservation, a total of 55,840 initiated cycles was reported. The number of initiated cycles by institution ranged from 23 to 2765, where 21% of reporting centres carried out 100 cycles or fewer; 35% carried out between 100 and 250 cycles; 21% carried out between 251 and 500 cycles; 17% carried out between 500 and 1000 cycles; and 6% carried out 1000 or more cycles.

Assisted reproduction technique procedure and access

As in previous years, most initiated cycles were reported by Brazil, representing 44% of all cycles, followed by Argentina with 23% and Mexico 13% (Table 1). Also, most reporting clinics are located in these countries (35%, 17% and 18%, respectively).

Out of 36,494 initiated autologous cycles, which represents a 14.56% increase from 2012, 3.85% were cancelled before follicular aspiration. Therefore, a total of 35,089 oocyte retrieval procedures were carried out; in 96.25% of them, at least one mature oocyte was recovered. The preferred technique for insemination was ICSI (84.7%). In 25,590 cases, at least one embryo was transferred.

The three main reasons to explain the 7710 cases in which non-embroys were transferred despite having mature oocytes included 5168 cases of total embryo freezing; 1326 cases of absence of embryos for transfer; and 1216 cases of complete fertilization failure. Information on the 472 remaining cases includes a mixture of abnormal oocytes and absence of normal embryos for transfer.

One hundred and forty-five centres registered 10,912 frozen embryo transfer cycles representing 8.32% increase over the previous year and 144 centres reported 5927 fresh oocyte donation cycles representing 9.84% increase over 2012. In 63% of these cycles, oocytes were donated from exclusive donors, i.e., women that underwent ovarian stimulation and oocyte retrieval with the only purpose of donating their oocytes.

Pregnancies and deliveries

The clinical pregnancy rate (CPR) and delivery rate per oocyte retrieval in fresh autologous cycles are presented in Table 2. Both CPR and deliver rate per oocyte retrieval were higher in IVF cycles than in ICSI cycles (31.45% and 25.75%; P < 0.001; 25.39% and 20.61%; P < 0.001, respectively). In both instances, the differences reached statistical significance; however, the lack of random allocation of participants in each treatment category must be considered carefully before reaching any conclusion.

Table 2 Clinical pregnancy rate and delivery rate in fresh autologous IVF and intracytoplasmic sperm injection cycles in 2013.

Assisted reproduction technique procedure Oocyte retrieval Clinical pregnancy rate per oocyte retrieval (%) Delivery rate per oocyte retrieval (%)
ICSI 28,599 25.75 20.61
IVF 5173 31.45 25.39

ICSI, intracytoplasmic sperm injection.

In oocyte donation cycles, the CPR and delivery rate per embryo transfer were 47.25% and 39.05%, respectively (Table 3). Similar trends were observed in the case of frozen embryo transfer cycles: both CPR and deliery rate were higher when embryos were obtained from donated oocytes (Table 3) (38.17% and 33.58%; 31.09% and 26.65%, respectively). No differences, however, were found when delivery rate of frozen embryo transfer with donated oocytes was compared with autologous frozen embryo transfer in a subgroup of women younger than 35 years (33.19% and 31.50% respectively; RR 1.05, CI 95% 0.87 to 1.27). Delivery rate in 3640 embryo transfers using exclusive donors was 41.31% compared with 35.55% in 2287 embryo transfers among shared donors, i.e. women undergoing assisted reproduction and at the same time donated part of the oocytes recovered. The differences in delivery rate in these two conditions were highly significant (P = 0.015) in favour of using exclusive donors, OR 1.28 (CI 95% 1.14 to 1.42). It is not possible from the data collected in the registry to gather information on the different criteria used to decide which and how many oocytes were donated for third-party reproduction.

Table 3 Clinical pregnancy rate and delivery rate in oocyte donation, frozen embryo transfer (oocyte donation) cycles in 2013.

Assisted reproduction technique procedure Embryo transfer Clinical pregnancy rate per embryo transfer (%) Delivery rate per embryo transfer (%)
Oocyte donation 5927 47.25 39.05
FET 10,912 33.58 26.65
Oocyte donation (FET) 2507 38.17 31.09

FET, frozen–thawed embryo transfer.

Age of women undergoing assisted reproduction technique procedures and delivery rate

The mean age of women undergoing autologous IVF–ICSI was 36.38 years (SD 4.55). The distribution of initiated IVF–ICSI cycles according to woman's age is shown in Figure 1. Most cycles were carried out in women aged 35–39 years (40.13%). Furthermore, 30.65% of women undergoing IVF–ICSI were 40 years or older. In the case of fresh oocyte donation cycles, the mean age of woman reached 41.49 years (SD = 5.01); of which 50.76% were 43 years and older.

rbmo1522-fig-0001

Figure 1 Age distribution of women initiating autologous or heterologous IVF and intracytoplasmic sperm injection cycles, 2013.

As expected, the delivery rate per embryo transfer in autologous assisted reproduction techniques was significantly influenced by the age of the female partner. The effect of age on the delivery rate and embryo transfer in fresh cycles is shown in Figure 2 and Figure 3. Delivery rate per embryo transfer decreased with the age of women, from 38.37% in the younger population to 9.12% in the oldest group (P < 0.001). In the case of oocyte donation, the age of oocyte recipients did not systematically affect the delivery rate per embryo transfer, as seen in Figure 3. Delivery rate per embryo transfer reached 41.42% in women aged 34 years or younger (n = 478 embryo transfer); 42.26% in women aged 35–39 years (n = 1053 embryo transers); 40.17% in women aged 40–42 years (n = 1419 embryo transfers); and 37.03% in women aged 43 years older (n = 3027 embryo transfers) (P = 0.009).

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Figure 2 Effect of age category of female partner on the delivery rate per embryo transfer in fresh autologous IVF and intracytoplasmic sperm injection, 2013.

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Figure 3 Effect of age of female partner on the delivery rate per embryo transfer in fresh autologous and heterologous IVF and intracytoplasmic sperm injection, 2013.

Number of embryos transferred and multiple births

Fresh autologous IVF–ICSI

The outcome of 25,590 fresh autologous IVF/ICSI embryo transfers with a mean number of embryos transferred of 2.1 (SD = 0.71) is shown in Table 4: 2.2 when cleaving-embryos were transferred, and 2.0 when blastocyst-stage embryos were transferred. In most cases (57.2%), two embryos were transferred; whereas the transfer of three embroys and four or more embryos represented 23.4% and 2.5% of embryo transfers, respectively. The transfer of more than two embryos was not associated with a significant increase in the CPR: 39.15% when two embryos were transferred, 39.28% when three embryos were transferred, and 35.26% when four or more embryos were transferred. The proportion of triplet deliveries, however, increased with the transfer of more than two embryos. When two embryos were transferred, the proportion of triplet deliveries was 0.60%; increasing to 2.33% with the transfer of three embryos and 4.88% when more than three embryos were transferred.

Table 4 Clinical pregnancy rate, delivery rate and gestational order according to the number of embryos transferred in fresh autologous IVF and intracytoplasmic sperm injection cycles in 2013.

Number of transferred embryos Total embryo transfer CPR per embryo transfer (%) Deliveries
Number % Total (number) Delivery rate per embryo transfer (%) Singleton (%) Twin (%) ≥Triplets (%)
1 4323 16.9 18.07 583 13.49 97.60 2.40 0.00
2 14,648 57.2 39.15 4652 31.76 76.74 22.66 0.60
3 5978 23.4 39.28 1891 31.63 75.73 21.95 2.33
≥4 641 2.5 35.26 164 25.59 78.66 16.46 4.88
Total 25,590 100 35.50 7290 28.49 78.19 20.71 1.09

CPR, clinical pregnancy rate.

Fresh heterologous IVF–ICSI

The outcome of 5927 transfer cycles with oocyte donation, with a mean number of embryos transferred of 2.2 (SD = 0.61) is shown in Table 5: 2.3 when cleaving-embryos were transferred, and 2.0 when blastocyst-stage embryos were transferred.

Table 5 Clinical pregnancy rate, delivery rate and gestational order according to the number of embryos transferred in fresh heterologous IVF and intracytoplasmic sperm injection cycles in 2013.

Number of transferred embryos Total embryo transfer CPR per embryo transfer (%) Deliveries
Number % Total (number) Delivery rate per embryo transfer (%) Singleton (%) Twin (%) ≥Triplets (%)
1 416 7.02 40.87 136 32.69 97.06 2.94 0.00
2 3901 65.82 47.73 1522 39.02 68.73 30.75 0.53
3 1511 25.49 48.71 632 41.83 62.34 34.18 3.48
≥4 99 1.67 36.36 30 30.30 60.00 30.00 10.00
Total 5927 100 47.27 2,320 39.14 68.53 30.04 1.43

CPR, clinical pregnancy rate.

In 65.82% of cases, two embryos were transferred, and three or more embryos were transferred in 27.16%. As with autologous reproduction, the transfer of more than two embryos was not associated with a significant increase in the CPR (47.73% with two embryos, 48.71% with three embryos and 36.36% with four or more embryos transferred). The delivery of triplets, however, increased from 0.53% with the transfer of two embryos to 3.48% with three and 10.0% with the transfer of four or more embryos.

Autologous frozen–thawed embryo transfers

The outcome of 10,912 frozen embroy transfer cycles, with a mean number of embryos transferred of 2.0 (SD = 0.65) is shown in Table 6. In most cases (61.84%), two embryos were transferred. Compared with the transfer of two embryos, the transfer of three and four or more embryos was not associated with a significant increase in CPR (35.11, 35.57 and 37.98%, respectively). The proportion of triplet deliveries was higher when three embryos were transferred (3.87%) than when two embryos were transferred (0.37%).

Table 6 Clinical pregnancy rate, delivery rate and gestational order according to the number of embryos transferred in autologous frozen–thawed embryo transfers in 2013.

Number of transferred embryos Total embryo transfers CPR per embryo transfer (%) Deliveries
Number % Total (number) Delivery rate per embryo transfer (%) Singleton (%) Twin (%) ≥Triplets (%)
1 2168 19.87 26.52 443 20.43 97.29 2.71 0.00
2 6748 61.84 35.11 1883 27.90 78.65 20.98 0.37
3 1867 17.11 35.57 542 29.03 72.69 23.43 3.87
≥4 129 1.19 37.98 35 27.13 71.43 28.57 0.00
Total 10,912 100 33.51 2903 26.60 80.30 18.74 0.96

CPR, clinical pregnancy rate.

Heterologous frozen–thawed embryo transfers

The outcome of 2507 cases of frozen embryo transfer with donated oocytes is shown in Table 7, with a mean number of embryos transferred of 2.08 (SD = 0.65). Compared with the transfer of two embryos and in contrast with autologous frozen embryo transfer cycles, the transfer of three and four or more embryos was associated with a significant increase in CPR (37.69%, 44.01%; 47.06%, respectively; P < 0.001). As was the case in autologous frozen embryo transfer, the proportion of triplet deliveries was higher when three embryos were transferred (2.96%).

Table 7 Clinical pregnancy rate, delivery rate and gestational order according to the number of embryos transferred in heterologous frozen–thawed embryo transfers in 2013.

Number of transferred embryos Total embryo transfers CPR per embryo transfer (%) Deliveries
Number % Total (number) Delivery rate per embryo transfer (%) Singleton (%) Twin (%) ≥Triplets (%)
1 388 15.48 31.20 87 22.42 96.55 3.45 0.00
2 1544 61.59 37.69 477 30.89 75.45 24.53 0.00
3 541 21.58 44.01 203 37.52 70.44 26.50 2.96
≥4 34 1.36 47.06 11 32.35 72.73 27.27 0.00
Total 2507 100 38.17 778 31.03 76.48 22.75 0.77

CPR, clinical pregnancy rate.

Elective single and double embryo transfer

Elective single embryo transfer and elective double embryo transfer accounted for 2% (n = 512) and 23.24% (n = 5892) of autologous fresh embryo transfers, respectively. Delivery rate per embryo transfer reached 30.08% with elective single embroy transfer and 41.62% with elective double embroy transfer, which was significantly higher than non-elective transfers. Delivery rate in non-elective single embryo transfers was only 11.26% in 3811 transfers (P < 0.0001), and non-elective double embryo transfer was 25.13% in 8756 embryo transfers (P < 0.0001). In women aged 34 years or younger, delivery rate after elective single embryo transfer and elective double embryo transfer reached 39.07% and 47.82%, respectively.

Perinatal outcome

A total of 16,042 live births were registered after treatment in 2013. Of these, 8621 were born after autologous fresh transfers, 4003 after heterologous fresh and frozen transfers, and 3418 after autologous frozen embryo transfer (Table 8).

Table 8 Perinatal mortality according to gestational order in 2013.

Assisted reproduction technique procedure Singleton Twin ≥Triplets
Live birth Still birth Early neonatal death Live birth Still birth Early neonatal death Live birth Still birth Early neonatal death
IVF–ICSI/othera 5541 158 33 2863 112 55 217 10 14
FET 2270 70 8 1068 23 11 80 3 1
Oocyte donation 1577 16 9 1371 11 14 100 4 0
FET (oocyte donation) 590 3 5 347 2 7 18 0 0
Total 9978 247 55 5649 148 87 415 17 15
Perinatal mortalityb 29.38 39.94 71.59

a Combined IVF and ICSI cases and no certainty as to which embryos were transferred.

b Proportion of still births plus early neonatal death per 1000 births.

FET, frozen embryo transfer; ICSI, intracytoplasmic sperm injection.

The duration of gestation was reported in a total of 11,008 deliveries from both autologous and heterologous reproduction. Among 8385 singletons, the mean gestational age at delivery was 37.55 weeks of amenorrhoea. This mean dropped to 35.22 weeks in 2500 twin deliveries, 32.63 weeks in 120 triplets, and 29.67 weeks in three cases of quadruplets (P < 0.001). The relative risk for prematurity was 4.9 (95% CI 4.5 to 5.3) in twins, and 8.7 (95% CI 7.6 to 10.0) in triplets and higher.

The percentage of preterm births was 7.51% in singletons, 36.58% in twins, 65.52% in triplets and 100.00% in quadruplets (P < 0.0001). The percentage of very preterm birth was 1.85% in singletons, 7.13% in twins, 21.38% in triplets and 66.67% in quadruplets (P < 0.0001).

How preterm birth affects perinatal mortality can be inferred from Table 8. An increase in gestational order was significantly (P < 0.0001) associated with pre-term birth and, consequently, a rise in perinatal mortality. Singletons had a perinatal mortality of 29.38 per 1000, compared with 39.94 per thousand in twins and 71.59 per thousand in triplets and more (P < 0.0001). Furthermore, perinatal mortality among singletons born after fresh oocyte donation was only 15.6 per 1000 and 13.4 per thousand for frozen–thawed oocyte donation.

Sponaneous abortion rate

The spontaneous abortion rate in women undergoing fresh IVF–ICSI was 18.29%, which increased significantly with the age of the female partner, reaching 36.43% in women aged 42 years and older (P < 0.0001). The spontaneous abortion rate in women undergoing fresh oocyte donation was 16.48%, and no significant differences were found according to the age of recipients; the spontaneous abortion rate reached 13.10%, 15.98%, 14.24% and 18.31% in women aged 34 years and younger, 35–39 years, 40–42 years and 43 years and older, respectively (Figure 4).

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Figure 4 Effect of age of female partner on the miscarriage rate, 2013.

The spontaneous abortion rate in women undergoing frozen embryo transfer was 19.52%. No subgroup analysis was carried out in this case, as the RLA reports the age of the woman at the time of embryo transfer not at the time of embryo freezing.

Preimplantation genetic diagnosis

The RLA registers PGD and preimplantation genetic screening (PGS) together. Eighty-six centres from 12 different countries reported 1920 cycles of PGD. Most were carried out in blastocysts (55.79%). Overall, 708 embryo transfers took place. The mean age of women was 38 years (range 21–49 years). A mean of four embryos were analysed in each cycle, and a mean of one embryo was reported as normal. Two hundred and eight clinical pregnancies were registered and 172 deliveries (145 singletons and 27 twins); therefore, a total of 199 healthy babies were born.

The use of PGD was not associated with a significant decrease in spontaneous abortion rate, reaching 16.98%, 11.24%, 21.57% and 35.71% in women aged 34 years or younger, 35–39 years, 40–42 years and 43 years or older, respectively.

Assisted hatching

Institutions in 10 different countries reported 5687 cycles with assisted hatching. The mean age of women undergoing assisted hatching was 37 years (range 19 to 49 years), and the mean number of embryos transferred was 2.2 (SD = 0.80). Of the 4767 embryo transfers reported, a clinical pregnancy was achieved in 1775 cases, resulting in 1400 deliveries (29.37%). Of these, 1106 were singletons, 276 twins and 18 triplets.

Implantation rate

The implentation rate in fresh IVF–ICSI cycles reached 20.98%. It was significantly associated with the age of the woman: 27.23% in women under 35 years, 20.09% in women aged 35–39 years, 12.88% in women aged 40–42 years, and 7.99% in women over 42 years (P < 0.001). It was also significantly associated to the developmental stage at embryo transfer: 19.05% when cleaving-embryos were transferred, and 28.58% when blastocyst-stage embryos were transferred (P < 0.001). The use of PGD was also associated with an increase in implantation rate. Indeed, implantation rate of chromosomally normal embryos reached 32.02% in women under 35 years, 30.67% in women aged 35–39 years, 22.22% in women aged 40–42 years, and 19.15% in women over 42 years.

Intrauterine insemination

Ninety-four clinics in 10 countries reported 6250 cycles of intrauterine insemination with semen of the male partner. The delivery rate per cycle was 14.91%, 10.04% of which were twin deliveries and 1.41% triplets-and-higher order. As with other fertility treatments, the age of the female partner, strongly influenced results. Delivery rate after intrauterine insemination dropped from 18.4% per cycle in women under 35 years, to 13.4% in women aged 35–39 years. In women aged between 40 and 42 years, delivery rate was 7.1% dropping to 3.5% in women aged over 42 years. Seventy-six clinics in 10 countries reported 963 cycles of donor. The delivery rate per cycle (23.36%) was higher than for autologous intrauterine insemination. The multiple delivery rate was 8.56%: 7.66% for twins and 0.90% for triplets and higher.

Cumulative and total delivery rate

The cumulative delivery rate according to women's age is shown in Table 9. As expected, the most meaningful increment in delivery rate was seen in younger women (<35 years years), where the delivery rate per oocyte pick up increased from 29.21% in all fresh cycles to 41.26%, whereas in women aged 43 years and older, it only increased from 5.49–9.72%. The cumulative delivery rate in autologous IVF–ICSI is shown in Figure 5, according to the age of the female partner.

Table 9 Cumulative delivery rate in autologous IVF and intracytoplasmic sperm injection cycles with at least one oocyte recovered in 2013.

<35 years 35–39 years 40–42 years ≥43 years
Total oocyte retrieval 10,390 14,152 7186 3313
Deliveries IVF–ICSI 3035 3164 909 182
Deliveries FET 1252 1156 355 140
Cumulative delivery rate (%) 41.26 30.53 17.59 9.72

FET, frozen embryo transfer; ICSI, intracytoplasmic sperm injection.

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Figure 5 Cumulative delivery rate in autologous IVF/ICSI cycles with at least one oocyte recovered in 2013.

Fertility preservation

Sixty-six centres from 12 countries reported 1616 initiated cycles for fertility preservation; 74% of these were carried out in healthy women. Overall, the mean age of women undergoing this procedure was 37 years (SD = 4.7). The mean number of oocytes preserved was eight (range from 0 to 39). In all cases, the technique for cryopreservation was vitrification. Ten cases were reported of OHSSS and one case of haemorrhage.

Complications

Clinics reported 218 cases of severe ovarian hyperstimulation syndrome (where hospitalization or medical interventions were required), corresponding to a rate of 1.97%. Other less frequent complications included 59 cases of haemorrhage and 21 cases of infection. It is likely, however, that complications are under-registered.

Discussion

This is the 25th version of the RLA, which has been published consectively since 1990. The major change in data collection was introduced for cycles carried out during 2011 when a cycle-based registry was implemented.

Between 2012 and 2013, initiated cycles increased by18%; from 47,326 cycles reported in 2012 to 55,840 reported in 2013. This increase is not explained only by an increase in the number of countries and centres registering their data, but also by an increase in the mean number of cycles registered by many institutions. In 2012 the mean number of cycles reported by clinics was 309, increasing to 355 in 2013 (Zegers-Hochschild et al., 2015). Nevertheless, with an access of 425 cycles per million women aged 15–45 years, Latin America is far behind developed countries (Ishihara et al., 2015). It is worth mentioning that countries like Argentina, with a consistent policy towards recognizing the right to found a family as a human right, have the highest number of assisted reproduction technique cycles per population. It is likely that Argentina and now Uruguay, the only two countries in Latin America with laws providing universal access to assisted reproduction techniques, will increase the number of procedures per million populations in these countries over the rest of the region. Countries in which access to treatments depends on the individual capacity to pay will remain with low coverage.

Many centres have adopted the policy of delaying embryo transfer by freezing all embryos in order to transfer them in a subsequent cycle. In 2013, 5168 cycles were reported, representing a major increase over the 3393 cases reported in 2012.

No significant difference was found in pregnancy and delivery rate, mean number of embryos transferred ad the consistently low proportion of elective single embryo transfer or elective double embryo transfer compared with the previous report (Zegers-Hochschild et al., 2015). Although this is partly influenced by the fact that assisted reproduction technique treatment in Latin America is mostly funded by the couples themselves, the reality is that, in the absence of a forced policy restricting embryo transfer to a maximum or two embryos, many centres transfer 3 or 4 embryos even in cycles with donated oocytes. In fact, in 2013 more than 25% of fresh autologous and heterologous assisted reproduction technique cycles had more than two embryos transferred; this was not associated with an increase in clinical pregnancy rate, but with a significant increase in the proportion of triplet and higher order births.

As expected, elective single embryo transfer and elective double embryo transfer were associated with higher CPR and delivery rate than the single and double non-elective transfers. The data presented here should encourage professionals in Latin America to restrict the number of embryos to be transferred to a maximum of two. When comparing this information with other national registries, it is important to bear in mind that, in Latin America, 30% of autologous assisted reproduction cycles initiated are in women who are 40 years and older and 70% are in women aged 35 years or older.

This report shows that even twin deliveries are associated with an increased risk of preterm births, and perinatal mortality. We have no explanation for the increased perinatal mortality in singletons compared with the previous year (29.3 and 25.2% per thousand respectively) and a simultaneous drop in perinatal mortality for twins and triplets (Zegers-Hochschild et al., 2015). Overall, perinatal mortality after assisted reproduction techniques is higher than in spontaneous pregnancies as expressed in global statistics by country (Jackson et al., 2004). The mean age of women delivering in most countries in Latin America, however, fluctuates between 20 and 30 years, whereas, more than 70% of autologous assisted reproduction treatments in the region are carried out in women aged 35 years or older, and 30% in women aged 40 years or older. Therefore, comparing perinatal mortality with the overall population needs to consider these variables.

When examining trends over the past 5 years, the mean number of embryos transferred in fresh autologous IVF–ICSI cycles dropped from 2.5 in 2008 to 2.1 in 2013. This results from a drop in the number of transfers with three and four or more embryos from 48.2% to 25.9%, and an increment in the number of single embryo transers from 11.9% to 18.1%. This was also accompanied by an increase in the number of frozen embryo transfer from 4225 to 10,912 in the past 5 years. Considering that the larger contributors to multiple births are young women, the mean number of embryo transfer in women under 35 decreased from 2.5 in 2008 to 2.3 in 2013. The question that needs to be answered is whether there has been an improvement in the performance of centres that justifies the reduction of embryos to be transferred without severely jeopardizing pregnancy or delivery rates. A way to address this question is to look at implantation rate as an indirect marker of the quality of each embryo generated and transferred. In women under 35 years, implantation rate was 23% in 2008 and 28% in 2013. Clinical pregnancy rates in 176 elective single embryo transfer carried out in 2008 was 29.0% compared with 38.3% of 515 elective single embryo transfers in 2013. Also, the proportion of blastocyst-stage embryo transfers in fresh autologous IVF–ICSI cycles increased in the past 5 years, from 1509 embryo transfers (8.2%) in 2008 to 5564 transfers in 2013 (15.2%), resulting in an increase in implantation rate from 20.0% in day 3 compared with 28.6% in day 5 of embryo culture. This information suggests that, although at a slow pace, centres are directing their efforts to strategies that help reduce the number of multiple births.

One of the main strengths of the RLA is the uniformity in terminology. All clinics reporting to RLA, use the glossary published in 2009 by the International Committee for Monitoring Assisted Reproductive Technologies and the World Health Organization (Zegers-Hochschild et al., 2009), translated into Spanish and Portuguese. The other strength is that the data voluntarily reported by each centre are periodically checked by an external and independent accreditation team, composed of a clinician and an embryologist, responsible for visiting every centre willing to provide its data to the RLA.

For the purpose of scientific comparisons among different therapeutic strategies, this registry does not allow for accurate comparisons; the main weakness is that registries report observational data, and not a summary of randomized controlled trials. As this present report examines observational data, the comparison of results cannot be considered as high-level evidence in favour or against certain procedures. This is the case with the significantly higher pregnancy and delivery rates achieved with IVF compared with ICSI cycles. It is quite possible that couples selected for IVF are expected to have better fertilization rate and can be more fertile couples altogether. Furthermore, the high proportion of ICSI over IVF does not seem to follow a biomedical reason (Ishihara et al., 2015). As seen over time, in countries in which assisted reproduction techniques are subsidized by public funds, the proportion of ICSI is relatively low, in the order of 60–70% in Australia and Northern Europe. In regions in which assisted reproduction techniques are paid directly by consumers, the proportion of ICSI rises above 80%; and this is the case in Latin America, the Middle East and several countries in Europe (Ishihara et al, 2015 and Zegers-Hochschild et al, 2011). Centres generally tend to favour the use of ICSI in order to avoid unexpected failed fertilization or low fertilization rate with regular IVF.

As the main drawback of assisted reproduction technique procedures reported in Latin America is the high proportion of multiple-gestations, and the perinatal complications that follow, strategies to reduce the number of embryos transferred must be enforced. One such strategy is to transfer blastocyst-stage embryos instead of cleaving embryos. Especially so in women aged 34 years and younger, in which the implantation rate of blastocysts is significantly higher than day 3 transfers (25.6% and 34.8%, respectively; P < 0.05). Furthermore, delivery rate per embryo transfer of elective single embryo transer in women aged younger than 35 years, rises from 17.42% when day-3 embryos are transferred, to 33.77% when blastocyst-stage embryos are transferred.

In summary, this is the fourth cycle-based registry published by the RLA. It is reassuring to patients and clinics that the results of assisted reproduction technique procedures carried out in the region are similar to other regions of the world (Ferraretti et al, 2013 and Zegers-Hochschild et al, 2013). Although Latin America is on the right path to reducing the number of embryos transferred, we need a more drastic reduction in order to prevent multiple births, or at least, high order multiples and decrease the corresponding perinatal complications.

Appendix. Supplementary material

The following is the supplementary data to this article:

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Table S1 Institutions and countries reporting to the Latin American Registry of ART, 2013.

References

  • Ferraretti et al, 2013 A.P. Ferraretti, V. Goossens, M. Kupka, S. Battacharya, J. de Mouzon, J.A. Castilla, K. Erb, V. Korsak, A. Nyboe Andersen. Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE – The European IVF-monitoring (EIM) Consortium, for The European Society of Human Reproduction and Embryology (ESHRE). Hum. Reprod. 2013;28:2318-2323
  • Ishihara et al, 2015 O. Ishihara, D. Adamson, S. Dyer, J. de Mouzon, K. Nygren, E. Sullivan, F. Zegers-Hochschild, R. Mansour. International committee for monitoring assisted reproductive technologies: world report on assisted reproductive technologies, 2007. Fertil. Steril. 2015;103:402-413
  • Jackson et al, 2004 R.A. Jackson, K.A. Gibson, Wu Y.W., M.S. Croughan. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet. Gynecol. 2004;103:551-563 Crossref
  • Zegers-Hochschild et al, 2009 F. Zegers-Hochschild, G.D. Adamson, J. de Mouzon, O. Ishihara, R. Mansour, K. Nygren, E. Sullivan, S. Vanderpoel. International Committee for Monitoring Assisted Reproductive Technology; World Health Organization. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology. Fertil. Steril. 2009;92:1520-1524 Crossref
  • Zegers-Hochschild et al, 2011 F. Zegers-Hochschild, K. Nygren, O. Ishihara. The impact of legislation and socioeconomics factors in the access to and global practice of assisted reproductive technology (ART). D.K. Gardner, A. Weissman, C.M. Howles, Z. Shoham (Eds.) Textbook of Assisted Reproductive Medicine 4th ed. (Informa Healthcare, London, UK, 2011) 441-450
  • Zegers-Hochschild et al, 2013 F. Zegers-Hochschild, J.E. Schwarze, J.A. Crosby, C. Musri, M.C. Borges de Souza. Assisted reproductive technologies (ART) in Latin America: the Latin American Registry, 2011. JBRA Assist. Reprod. 2013;17:216-223
  • Zegers-Hochschild et al, 2015 F. Zegers-Hochschild, J.E. Schwarze, J.A. Crosby, C. Musri, M.C. Borges de Souza. Assisted reproductive technologies in Latin America: the Latin American Registry. Reprod. Biomed. Online. 2015;30:43-51 Crossref
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Fernando Zegers-Hochschild is the founder and chairman of the Latin American Registry of Assisted Reproduction and co-founder and Vice-Chair of the International Committee for Monitoring Assisted Reproduction. For 30 years he has served on various World Health Organization task forces, and acted as expert to the United Nations and the Inter American Court of Human Rights in issues related with human reproduction and reproductive rights. His main research interests include monitoring trends in the safety, efficacy and influence of cultural diversity on the practice of assisted reproduction, as well as bioethical challenges resulting from its use. He has authored over 120 scientific articles and book chapters.

Footnotes

a Unit of Reproductive Medicine Clínica Las Condes, Chile

b Program of Ethics and Public Policies in Human Reproduction, University Diego Portales, Chile

c Latin American Network of Assisted Reproduction (REDLARA), Uruguay

d Unit of Reproductive Medicine Clínica Monteblanco, Chile

e Unifertes, Venezuela

* Corresponding author.