RBMOnline - Vol 2. No 2. 129 137 Reproductive BioMedicine Online webpaper 2000/045 on web 12 Mar 2001 Outlook Results of assisted reproduction techniques in Latin America* Dr Fernando Zegers- Hochschild Fernando Zegers-Hochschild obtained his degree in Medicine from the University of Chile in 1974. Postgraduate training followed, also at the University of Chile in obstetrics and gynecology, and endocrinology. He held a WHO Fellowship in Human Reproduction at University of Sheffield, UK in 1979. Since then he has obtained many distinctions including the Doctor Juan Malfanti award of the Chilean Society of Obstetrics and Gynecology in 1986, and Doctor of the Year award, Clinica Las Condes, in 1989.He is currently Director of the Unit of Reproductive Medicine, Clínica Las Condes, Santiago, Chile. He is co-founder and member of the board of directors of the Chilean Institute of Reproductive Medicine, and founder and responsible for the Latin American Registry of Assisted Reproduction. In 1995 2000 he was Founder and Executive Director of the Latin American Network of Assisted Reproduction. He is a member of many national and international scientific societies. Current research interests include follow-up and outcome of multiple pregnancies associated with assisted reproduction techniques and preconception genetic diagnosis. Dr Zegesr-Hochschild has published widely both nationally and internationally and includes among his achievements the production of a CD Rom entitled Journey to Life (in English and Spanish). He continues to run regular courses for Master s Degree students in Reproductive Biology at the University of Chile. F Zegers-Hochschild 1, A Mackenna, E Fernández, MS Sepúlveda Unidad de Medicina Reproductiva (Unit of Reproductive Medicine), Clínica Las Condes, Lo Fontecilla 441, Santiago, Chile. 1 Correspondence: Tel. 56-2-2104499; fax 56-2-2104473; e-mail umrclc@entelchile.net Abstract The fact that today it is possible to write a comprehensive report on assisted reproduction technologies in Latin America is the result of a serious and systematic effort, accomplished by more than 80 centres, from Mexico to Chile. Over the past 10 years, these centres representing the vast majority of assisted reproductive treatment cycles performed in Latin America, have agreed voluntarily to report their work to our regional registry using a pre-established format. Furthermore, during 1999 and part of 2000, all centres were visited by a team of biologists and clinicians, who evaluated for consistencies in the data reported. This activity also included an evaluation of personnel, facilities, etc. It can be proudly said that the data reported are a true reflection of the actual situation in our region. Keywords: ART, assisted reproductive technologies, Latin America Introduction Over the past few decades, remarkable progress has been made in developing modern reproductive technology. Latin America has not been untouched by these developments and serious and systematic effort has been placed in the transfer of technology and its application for the benefit of our population. In the seventies, Latin America contributed significantly to research and development of various contraceptive methods (Pérez Palacios and Garza-Flores, 1994). Today, our region continues to play a decisive role in developing new and efficient methods for fertility regulation, following a tradition of more than three decades. This is partly due to the fact that numerous international agencies have contributed in the strengthening of human resources, and in the establishment of facilities for family planning programs in institutes adhered to university and national health systems. On the other hand, at least theoretically, our countries should obtain benefits from these developments. Unfortunately this has not always proved to be true. In contrast, the desire to have more children in a highly populated region is viewed as being low priority. Furthermore, in the absence of legislation regulating the practice of assisted reproduction, access to fertility treatments is not on the agenda *Chapter taken from a forthcoming book in Spanish on Modern Assisted Conception edited by RG Edwards and F Risquez. Supported by Serono.
of national health policies and companies responsible for health insurance do not cover expenses related to fertility treatments. Furthermore, for many legislators, procedures such as in-vitro fertilization (IVF) and embryo transfer are considered morally unacceptable and a luxury that should not be sustained with state funds. An extreme example of this moral dictatorship is Costa Rica where the high court has recently decided that IVF/embryo transfer is morally unacceptable and illegal, banning IVF/embryo transfer from the country. These are some of the conditions which contribute to a restricted and unequal access to modern reproductive technology in Latin America. The number of women with access to assisted reproduction technology does not exceed 0.7 2.8% of those who could really benefit from these treatments (Zegers-Hochschild, 1999). Today, more than 90% of the centres offering assisted reproduction techniques in Latin America, are private institutions, do not receive university or government support, and restrict access only to couples who can pay the high costs involved. The fact that most of the centres performing assisted reproductive techniques in Latin America did not evolve from or have no relationship with university settings has contributed to poor innovative development when compared to contraceptive research and development. Instead, the region has placed most of its effort in the transfer of technology and its application with increasing efficiency. This has indeed contributed to solve infertility in thousands of couples. Since 1984 when the first IVF/embryo transfer pregnancy in Latin America was reported, assisted reproductive techniques has spread throughout the entire region. In 1990, a multinational registry of assisted reproduction was initiated. This document, known as the Registro Latinoamericano de Reproducción Asistida (RLA) and published annually since 1992 represents more than 80% of initiated cycles in centres located from Mexico in the north to Chile in the south. All participating centres have voluntarily agreed to register their information using a fixed format provided in a software that considers type of stimulation protocols, clinical pregnancy and implantation rates according to age of female partner and number of transferred embryos. It also registers the outcome of pregnancies, gestational age at delivery, weight of newborns and perinatal mortality. The software also allows for comparison between different treatment modalities such as intracytoplasmic sperm injection (ICSI), IVF/embryo transfer and the transfer of cryopreserved embryos. Once the data is received, it is checked for inconsistencies, compiled, analysed and published, maintaining anonymity of all the participating centres. The purpose of this article is to provide gynaecologists with solid information on prognostic factors affecting the outcome of assisted reproductive techniques in Latin America, relevant for a proper counselling of couples seeking assisted reproductive techniques. The data presented here have been obtained from procedures initiated during 1998, and deliveries up to September 1999. Whenever relevant, longitudinal analysis has been made using data obtained from 1992 to 1998. Further information on the centres which form part of this Network may be obtained from www.redlara.com Results of assisted reproduction techniques in Latin America In 1990, 19 centres reported a total of 2461 initiated cycles. In 1998, 84 centres covering almost the whole of Latin America, reported 12 271 procedures. Between 1990 and 1998, the RLA included 32 389 assisted reproductive cycles that resulted in 6480 live births (Figure 1) Figure 1. Results of assisted reproduction techniques in Latin America 1990 1998 (see Registro Latinoamericano de Reproducción Asistida, 1998). Characterization of patients and type of procedures It has been well established that the age of the female partner is by itself one of the most important prognostic factors in any infertility treatment. Increasing age negatively affects ovarian reserve and therefore, the number of oocytes available. Moreover, as age advances, the proportion of oocytes with structural alterations is greater (Battaglia et al., 1996), as is the proportion of oocytes with alterations in the number of chromosomes (aneuploidies). While these factors may not affect fertilization rates, they do affect implantation rates and the occurrence of subclinical and clinical abortions (Munné et al., 1995). In order to understand the efficacy of a given therapy, it is necessary to describe the age category of the population subjected to a specific treatment. In Latin America, the population with access to modern methods of assisted reproduction has been changing. In 1990, 66.5% of the women were <35 years of age and only 8.7% were >40. In 1998, only 50% of the population was <35 and 14% was >40 (Figure 2). When the results are analysed longitudinally this condition needs to be considered in order to establish if therapeutic efficacy has in fact improved with time.
Figure 2. Attempted oocyte retrievals according to maternal age IVF (see Registro Latinoamericano de Reproducción Asistida, 1998). Another remarkable change that has occurred in Latin America (as in most of the world) is the increasing use of micromanipulation techniques. In 1990, 70% of the procedures were IVF/embryo transfer and the remainder were mostly gamete intra-fallopian transfer (GIFT) as well as other procedures such as embryo and zygote transfer to the Fallopian tube, or a combination of these procedures. Since 1992, when a pregnancy using ICSI was first reported (Palermo et al., 1992), this technique rapidly spread to all parts of the world. In 1993, only 4.2% of centres included in the RLA reported ICSI results, which accounted for 3.7% of oocyte retrievals. In 1998, 78% of the centres reported ICSI procedures and this methodology accounted for 60% of the procedures performed in the region during that year (Figure 3). At least two comments can be made: the first has to do with the speed of technology transfer. The first pregnancy with IVF/embryo transfer in Latin America took ~6 years following the announcement by Steptoe and Edwards to the international community (1978). The time between the first reported case of ICSI and the application of this technology in Latin America took only 1 year. The second has to do with the disproportionate increase in the frequency of ICSI procedures compared with less invasive procedures such as IVF/embryo transfer. In fact, it is surprising that such recent technology where the eldest born has not even experienced adolescence is preferred by many centres as a routine procedure over IVF/embryo transfer. Indeed, there are medical conditions that require assisted fertilization; however, according to the frequency of male factor infertility as a diagnostic category, more ICSI procedures are being performed than are actually required. For example, in 1990, 60% of diagnostic infertility categories were tubal factors. In 1998, 37% of treatments were due to factors associated with abnormalities in the Fallopian tube, adhesions, etc. and only 11% were considered to be due to male factors. This is in contrast with the 60% of ICSI procedures performed during that year. Figure 3. Percentage of the total number of attempted oocyte retrievals according to procedure (see Registro Latinoamericano de Reproducción Asistida, 1998).
Table 1. Treatment cycles and clinical pregnancy rate according to type of procedure (1998). P r o c e d u r e s e IVF GIFT Other Micromanipulation ICSI + IVF Soft/TOMI Assisted hatching Cryopres -ervation Oocyte donation Fresh Thawed Cycles initiated (n) 4595 136 206 Cycles cancelled (n) 630 6 3 Attempted oocyte retrievals (n) a 3965 130 203 4283 989 98 957 Transfers (n) b 3501 118 194 3870 755 71 916 708 882 59 Clinical pregnancies (n) c 973 38 58 1124 293 29 243 123 333 14 Delivieries with >=1 live birth (n) d 756 30 49 860 180 23 164 90 255 10 Cycles cancelled (%) 13.7 4.4 1.5 Transfers/attempted oocyte retrieval (%) 88.3 90.8 95.6 Clinical pregnancies/attempted oocyte retrieval (%) 24.5 29.2 26.2 26.2 29.6 29.6 25.4 Clinical pregnancies/transfer (%) 27.8 32.2 29.0 29.0 38.8 40.8 26.5 17.4 37.8 23.7 Deliveries with one or more livebirths per: Attempted oocyte retrieval (%) 19.1 23.1 19.8 20.1 18.2 23.5 17.1 Transfer (%) 21.6 25.4 21.9 22.2 23.8 32.4 17.9 12.7 28.9 16.9 Clinical pregnancy (%) 77.7 78.9 75.5 76.5 61.4 79.3 67.5 73.2 76.6 71.4 ICSI a Attempted oocyte retrieval = transvaginal and laparoscopic follicular aspirations, independently of whether oocyte(s) were retrieved. b Transfers = transfer of one or more concepti (embryos) and/or gametes to the uterus and/or to the Fallopian tube c Clinical pregnancy = intrauterine gestations, documented by ultrasound, with at least one gestational sac. d Delivery = live born after completing 20 weeks gestation. e The total number of procedures performed during 1998 includes: Cycles initiated (IVF, GIFT and other) = 4937; cycles with attempted oocyte retrievals (ICSI, ICSI + IVF, ICSI+GIFT and assisted hatching = 6327; Cycles transferred (cryopreserved and oocyte donation) = 1649 Overall results of different techniques Table 1 analyses overall results obtained with the different reproductive techniques. Clinical pregnancy and live birth delivery rates are expressed according to the number of cycles with follicular aspiration and/or embryo transfer. It is not possible to compare pregnancy rates for the different treatment alternatives since the selection criteria to use one alternative or another are not perfectly comparable. As can be seen from this table, the number of GIFT procedures accounted for only 1% of the total. This low number of cases makes it difficult to compare the results of this technique with IVF/embryo transfer or ICSI. On the other hand, if we consider that the fecundability in our species is ~25% per cycle (Tietze, 1956; Spira et al., 1985), the overall results with GIFT exceed this. This may be partly due to the age of the female partner and the lack of other pathological factors. The clinical pregnancy rate by aspiration and by transfer are very similar for IVF/embryo transfer and ICSI, being 24.5 versus 26.2% and 27.8 versus 29.0% respectively (Table 2).In order to provide couples who seek advice with adequate information, it is necessary to inform them of the overall chances of having a healthy newborn with one technique or another. With IVF/embryo transfer, the delivery rate, by transfer, with one or more healthy child is 21.6%, and with ICSI, 22.2%. This means that after one attempt, the probability of not delivering a baby is 78%. Table 2. Pregnancy and delivery rates in IVF and ICSI in 1998. IVF ICSI Pregnancy rate/ attempted oocyte retrieval (%) 24.5 26.2 Pregnancy rate/transfer (%) 27.8 29.0 Delivery rate/transfer (%) 21.6 22.2 There were no significant differences.
Effect of maternal age on pregnancy rates in IVF/embryo transfer In Tables 3 and 4, the effect of the maternal age on clinical pregnancy rates and implantation rates (number of gestational sacs/number of embryos transferred) are shown. As can be seen, the age of the woman negatively affects pregnancy rate. If the number of embryos transferred and the diagnostic category is maintained constant, age becomes an independent variable. Out of a total of 801 IVF/embryo transfer cycles with three embryos transferred, the clinical pregnancy and embryo implantation rates in women under 35 was 31.4% (142/453; Table 5) and 14.3% respectively. These rates are significantly higher than those found in women over 40 years (5.3% and 1.8%, respectively). In women between 35 and 39, the pregnancy and implantation rates were 27.2% (74/274) and 10.7%, respectively (Table 5). In this age group, when three embryos are transferred, the pregnancy and implantation rates do not differ from the younger age group. Table 3. Clinical pregnancy rate (%) according to the number of embryos transferred and maternal age: IVF. <35 16.7 (27/162) 21.3 (55/258) 31.4 (143/455) 39.8 (216/543) 36.9 (73/198) 34.3 (36/105) 35 39 13.9 (22/158) 18.2 (41/225) 27.2 (75/276) 29.0 (114/393) 41.4 (75/181) 34.5 (30/87) >39 8.5 (9/106) 15.2 (15/99) 5.3 (4/75) 18.9 (17/90) 18.2 (10/55) 31.4 (11/35) Total 13.6 (58/426) 19.1 (111/582) 27.5 (222/806) 33.8 (347/1026) 36.4 (158/434) 33.9 (77/227) Table 4. Implantation rate (%) according to the number of embryos transferred and maternal age: IVF. <35 17.9 (29/162) 11.8 (61/516) 14.3 (195/1365) 15.3 (333/2172) 13.6 (135/990) 8.4 (53/630) 35 39 14.6 (23/158) 11.3 (51/450) 10.7 (89/828) 9.8 (154/1572) 11.7 (106/905) 7.9 (41/522) >39 9.4 (10/106) 8.1 (16/198) 1.8 (4/225) 5.8 (21/360) 5.1 (14/275) 8.6 (18/210) Total 14.6 (62/426) 11.0 (128/1164) 11.9 (288/2418) 12.4 (508/4104) 11.8 (255/2170) 8.2 (112/1362) Table 5. Pregnancy and implantation rate according to maternal age when three embryos are transferred: IVF. Maternal age (years) Pregnancy rate (%) Implantation rate (%) <35 31.4 14.3 35 39 27.2 10.7 >39 5.3 1.8 Table 6. Pregnancy and implantation rate according to maternal age when three embryos are tranferred: ICSI. Maternal age (years) Pregnancy rate (%) Implantation rate (%) <35 33.0 14.6 35 39 30.0 10.6 >39 19.0 7.0
Table 7. Pregnancy and delivery rates in oocyte recipients with a mean age of 40 years. Number of transfers 882 Number of pregnancies 333 Number of deliveries 225 Clinical pregnancy rate (%) 37.8 Delivery rate (%) 28.9 The age of the female partner affects any treatment modality. In ICSI cases, where only three embryos are transferred, the clinical pregnancy rate for the three age groups (<35, 35-39, and >39 years) are 33.0, 30.0 and 19.0% respectively. The implantation rates in these three categories are 14.6, 11.6 and 7.0% respectively (Table 6) The impact of maternal age on reproductive efficiency is directly related to the capacity of an embryo to implant. This on the other hand is related to the availability of good quality oocytes, which have the potential to produce chromosomally normal embryos. Explanations of a genetic nature that support this fact can be found in Munné et al. (1995). Another way of looking at the effect of age and pregnancy, is to analyse the clinical pregnancy rate in recipients of donated oocytes. In 1998, 882 transfers were performed in recipients with a mean age of 40 and donors who, in general, were under 35. In the recipients, there were 333 clinical pregnancies, which resulted in 225 deliveries. The clinical pregnancy and delivery rates by transfer were 37.8 and 28.9% respectively. These rates are as good or even better than the pregnancy and delivery rates, by transfer, in women under 35 years of age undergoing IVF/embryo transfer (Table 7). The most relevant conclusion that can be drawn from this analysis is that maternal age affects reproductive efficacy following a mathematical model which operates the same way as it does in spontaneous reproduction, determined by the quality of oocytes and therefore, the quality of the resulting embryos. A deep understanding of this event is needed to offset the requirement for a high chance of pregnancy against the need to minimize the risks of multiple gestation. Effect of the number of transferred embryos on pregnancy rates in IVF/embryo transfer If numerous embryos are transferred, the chances of one of them being normal increases, allowing for the continuation of development. If this is true, the transfer of more than one embryo improves the probability of at least one of them resulting in gestation. Implantation rates for IVF/embryo transfer and ICSI according to the number of embryos transferred and sub-classified according to maternal age are shown in Tables 4 and 8. As can be seen, within a given age group, increasing the number of embryos does not increase the implantation rate, nor does it reduce it. Moreover, within each category of number of embryos transferred, the results are dramatically affected by maternal age. The differences in implantation rates are highly significant in women <35 and >39, 13.8% (806/5835) versus 6.0% (83/1374) respectively (P < 0.0001). It is, therefore, reasonable to accept that increasing maternal age affects pregnancy and implantation rates due to the quality of oocytes. If in a woman near 40 years of age, each embryo has lower reproductive potential, it would be reasonable to transfer a greater number of embryos. In this way, there would be a higher chance of one of them being able to implant. However, the risks of multiple gestation must be considered. This issue will be discussed below. Table 8. Implantation rate (%) according to the number of embryos transferred and maternal age: ICSI. <35 9.5 (14/147) 16.9 (113/670) 14.6 (274/1872) 14.1 (374/2652) 13.2 (156/1185) 10.9 (78/714) 35 39 12.7 (19/150) 7.0 (30/430) 11.6 (111/960) 11.0 (157/1432) 8.7 (68/780) 7.8 (31/396) >39 3.9 (4/103) 5.4 (13/240) 7.0 (21/300) 6.6 (23/348) 6.5 (14/215) 3.7 (6/162) Total 9.3 (37/400) 11.6 (156/1340) 13.0 (406/3132) 12.5 (554/4432) 10.9 (238/2180) 9.0 (115/1272)
Table 9. Rate of multigestation (%) according to the number of embryos transferred and maternal age: IVF. <35 7.4 (2/27) 10.9 (6/55) 31.5 (45/143) 38.0 (82/216) 53.4 (39/73) 27.8 (10/36) 35 39 4.5 (1/22) 24.4 (10/41) 16.0 (12/75) 26.3 (30/114) 30.7 (23/75) 26.7 (8/30) >39 11.1 (1/9) 6.7 (1/15) 0.0 (0/4) 23.5 (4/17) 40.0 (4/10) 36.4 (4/11) Total 6.9 (4/58) 15.3 (17/111) 25.7 (57/222) 33.4 (116/347) 41.8 (66/158) 28.6 (22/77) Table 10. Rate of extreme multigestation (%) according to the number of embryos transferred and maternal age: IVF. <35 0.0 (0/27) 0.0 (0/55) 4.9 (7/143) 14.8 (32/216) 20.5 (15/73) 11.1 (4/36) 35 39 0.0 (0/22) 0.0 (0/41) 2.7 (2/75) 7.9 (9/114) 8.0 (6/75) 10.0 (3/30) >39 0.0 (0/9) 0.0 (0/15) 0.0 (0/4) 0.0 (0/17) 0.0 (0/10) 27.3 (3/11) Total 0.0 (0/58) 0.0 (0/111) 4.1 (9/222) 11.8 (41/347) 13.3 (21/158) 13.0 (10/77) Table 11. Pregnancy outcome according to order of gestation: IVF and ICSI. Single Twin Triple Quadruplet or more Live births 1159 (98.9) 690 (97.6) 250 (90.3) 48 (92.3) Stillbirths: 20 27 weeks 5 (0.4) 11 (1.6) 15 (5.4) 4 (7.7) Stillbirths: 28 or more weeks 8 (0.7) 6 (0.8) 12 (4.3) 0 (0.0) Total 1172 707 277 52 Early neonatal deaths 8 (0.7) 11 (1.6) 6 (2.2) 5 (9.6) Values in parentheses are percentages. Figure 4. Rate of multigestation in IVF (see Registro Latinoamericano de Reproducción Asistida, 1998).
The problem of multiple gestation Multiple gestation is indeed a problem that has generated increasing interest throughout the world and is an issue of actual concern for Latin America. Figure 4 shows the overall multiple gestation rates (twins, triplets and greater) from 1990 to 1998. For at least the past 4 years, the rate of multiple gestation has been found between 28% and 30%, which is unacceptably high. However, what gives most cause for concern is the proportion of extreme multiple gestations (triplets and more). The overall and extreme multiple gestation rates in IVF/embryo transfer according to the number of embryos transferred and maternal age are shown in Tables 9 and 10. Overall, multiple gestation in women under 35 years, where three or four embryos are transferred, is relatively similar (31.5% and 38% respectively). However, triplets and more, increase from 4.9% to 14.8% reaching 20.5% when five embryos are transferred. Another cause for concern is the high rate of multiple gestation in women >40 years, when five or six embryos are transferred. If multiple gestation in women aged <35 is a serious problem, it is even more complicated in women over 40. In Latin America, neither abortion nor therapeutic reduction of embryos, are considered to be legal procedures. This makes the outcome of multiple gestations such as the rate of stillbirth and early neonatal death (Table 11) matters of considerable concern. This situation would be even more serious if perinatal morbidity were recorded by the RLA, since the rate of premature births is directly related to the order of gestation. Indeed, the high rate of multiple gestation in our region is a direct result of the number of embryos transferred. The mean number of embryos transferred, grouped according to maternal age is shown in Figure 5. In women <35, the average number of embryos transferred is between three and four. In a frequency distribution of this age group, 32% have four embryos transferred and 12% have five embryos transferred. Evidently, this is the most important factor that requires rapid changes in the region. In fact, the Latin American network is making considerable efforts in order to train participating centres to reduce the number of embryos transferred without affecting pregnancy rates, implementing cryopreservation in a larger number of centres. Embryo cryopreservation In 1983, the cryopreservation of human embryos was communicated as a therapeutic alternative (Trounson and Mohr, 1983). This new technology helps to avoid the transfer of more than two or three embryos, reducing the chances of multiple gestation. Moreover, by having more than one transfer after each ovum retrieval, this technique has also led to increased cumulative pregnancy rates, submitting the patient to only one cycle of ovarian stimulation and follicle aspiration. Cryopreservation can be performed either at the pronuclear stage or at other stages of embryo development. Although normal practice is to freeze 4-cell stage embryos, it can also be performed at the 8-cell stage or at the blastocyst stage of development. Of the 84 centres that reported to the registry in 1998, 53 centres generated a total of 705 transfers of frozen/thawed embryos and/or cells in pronuclear stage. Delivery rate per transfer was 12.8% (90/708), which is significantly lower than the delivery rate reported with fresh embryos 21.6% (756/3501) (P < 0.0001). Moreover, the frequency of spontaneous abortion was 26.0% (32/123), significantly higher than the 18.6% (180/968) (P < 0.0001) found with fresh embryos in IVF/embryo transfer (Table 12). It is surprising that the high rate of spontaneous abortions observed with cryopreservation is also found in women who receive thawed embryos of donated oocytes, whose donors are normally <35 years. Of the 59 transfers in this category, there were 14 pregnancies and four abortions, resulting in an abortion rate of 28.6 compared to 18.6% (62/333) obtained in 882 oocyte donation cycles with fresh embryos. The small number of cases of frozen embryos obtained after oocyte donation does not allow for meaningful statistics. It would be reasonable to assume that the high rate of abortion with frozen/thawed embryos is due to technical problems, as it is not related to maternal age but rather to a technical (freezing protocols) and chemical (cryopreservant) effect on embryos or fertilized oocytes. The only factor that might contradict this assumption is that, in regular practice, the best embryos from the cohort are transferred fresh and morphologically poorer embryos are cryopreserved. This could negatively affect the pregnancy, implantation, and abortion rates after the transfer of embryos with less vital potential. Table 12. Cryopreservation results. IVF (fresh) Cryopreservation No. of transfers 3501 708 No. of clinical pregnancies 973 123 No. of deliveries 756 90 Delivery rate per transfer (%) 21.6 12.7 Spontaneous abortion (%) 18.6 26.0 Figure 5. according to maternal age IVF (see Registro Latinoamericano de Reproducción Asistida, 1998).
Conclusion Since 1984, when the first pregnancy obtained by IVF-embryo transfer was reported in Latin America, this region has placed its effort in assisted reproductive techniques increasingly fast over the intervening years. However, for different reasons, the number of women with access to these kind of treatments does not exceed 0.7 2.8% of those who really need them in order to become pregnant. Since 1990 a comprehensive multinational registry has reported the results of assisted reproductive techniques cycles performed in the region. The age of the patients has changed through the years: in 1990 66.5% of women were under 35 and 8.7% were over 40 years of age, against 50% of women under 35 and 14% over 40 in 1998. This is relevant because implantation and pregnancy rates are negatively affected by the age of the female partner. When three embryos are transferred in women under 35 years old, implantation and pregnancy rates are 14% and 31.4% for IVF against 14.6% and 33% for ICSI. Another remarkable change through the years is the increasing use of ICSI: in 1993 this procedure was used in 3.7% of oocyte retreivals, against 60% of ICSI per oocyte retrieval reported in 1998, which is in contrast with the 11% of male factor reported and reflects the fact that there are many more ICSI procedures carried out than are actually required. Nowadays, a serious problem in Latin America is the rate of multiple pregnancy between 28% and 30%, which is the result of the number of embryos transferred. Among women <35 years old, 32% have four and 12% have five embryos transferred, values that need to be changed through the introduction of embryo cryopreservation in more centres. Registro Latinoamericano de Reproducción Asistida 1998 Red Latinoamericana de Reproducción Asistida. Santiago, Chile, 2000. Spira N, Spira A, Schwartz D 1985 Fertility of couples following cessation of contraception. Journal of Biosocial Science 17, 281 290. Steptoe PC, Edwards RG 1978 Birth after the re-implantation of a human embryo (letter). Lancet 2, 366. Tietze C 1956 Statistical contributions to the study of human fertility Fertility and Sterility 7, 88. Trounson A, Mohr L 1983 Human pregnancy following cryopreservation thawing and transfer of an eight-cell embryo. Nature 305, 707 709. Zegers-Hochschild F 1999 Cultural expectations from IVF and reproductive genetics in Latin America. In Jansen R, Mortimer D (eds) Towards Reproductive Certainty. Fertility and Genetics beyond 1999. Parthenon Publishing Group, New York, USA, pp. 435 439. In 1998 53 of 84 centres included in the registry reported 705 transfers after cryopreservation, with a significantly lower delivery rate (12.8%) and higher abortion rate (26%) when compared with results for fresh embryo transfers (21.6 and 18.6%), suggesting a technical problem. However, the fact that the best embryos are transferred fresh might have some influence on these results. Acknowledgements Our thanks go to the Red Latinoamericana de Reproducción Asistida for making this valuable information available. A description of participant centres can be found on www.redlara.com. References Battaglia DE, Goodwin P, Klein NA, Soules MR 1996 Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women. Human Reproduction 11, 2217 2222. Munné S, Alikani M, Tomkin G et al. 1995 Embryo morphology, developmental rates and maternal age are correlated with chromosome abnormalities. Fertility and Sterility 64, 382 391. Palermo G, Joris H, Devroey P, Van Steirteghem AC 1992 Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340, 17 18. Pérez-Palacios G, Garza-Flores J 1994 The contributions of Mexican scientists to contraceptive research and development. In Van Look PFA, Pérez-Paracios G (eds) Contraceptive Research and Development 1984 1994. The road from Mexico to Cairo and beyond. Oxford University Press, Oxford, UK. pp. 233 246.