Dr-kupka.de2

RBMOnline - Vol 8. No 3. 348-356 Reproductive BioMedicine Online; www.rbmonline.com/Article/1193 on web 29 January 2004 Previous miscarriages influence IVF andintracytoplasmatic sperm injection pregnancyoutcome Dr Markus S Kupka studied in Cologne, Tubingen and Bonn in Germany. He received his MDdegree in 1997. Following training, he was awarded his qualification in endocrinology andreproductive medicine from the University of Bonn, Germany in 1999, and in medicalinformatics in 2001. The latter scientific field deals with the storage, retrieval, sharing, andoptimal use of biomedical information, data and knowledge for problem solving and decisionmaking. Since 1997 he has been a co-worker and member of the Scientific Board of theGerman IVF-Registry (DIR). In 2001, he obtained a grant from the German Research Society(DFG) for a scientific project in Birmingham, Alabama, USA, in co-operation with the Centresfor Disease Control and Prevention at Atlanta, Georgia, USA. This project concentrates ontools for quality assessment and management in assisted reproductive techniques. Since2003 he has headed the working group for endocrinology and reproductive medicine at the most beautiful University Medical Centre of Obstetrics and Gynaecology in Germany.
MS Kupka1,4,5, C Dorn2, M Montag2, RE Felberbaum3, H van der Ven2, A Kulczycki4, K Friese11University Medical Centre of Obstetrics and Gynaecology, University of Munich, Maistr. 11, D–80337 Munich,Germany; 2University Medical Centre of Obstetrics and Gynaecology, University of Bonn, Sigmund Freud Strasse 25,D–53105 Bonn, Germany; 3University Medical Centre of Obstetrics and Gynaecology, University of Luebeck,Ratzenburger Allee 160, D–23538 Luebeck, Germany; 4School of Public Health, University of Alabama atBirmingham, 1665 University Boulevard, Ryals Building, Birmingham, AL 35294-0022, USA5Correspondence: Tel: +49 89 51604214; Fax: +49 89 51604918; e-mail: [email protected] Previous conceptions are one predictor for the outcome of assisted reproductive technology procedures. Approximately18–34% of clinical pregnancies following assisted reproduction procedures result in spontaneous abortion. The risk of suchpregnancy loss is believed to increase with women’s age, previous miscarriages and use of frozen–thawed embryos. This studyanalyses German IVF Registry data to examine the impact of previous miscarriages on the outcome of assisted reproductionprocedures. The dataset consists of a total of 174,909 assisted reproduction procedures performed between January 1998 andDecember 2000. Multiple logistic regression is used to assess the correlation between women’s age, spousal/partner change,and infertility diagnosis. It is demonstrated that any previous miscarriage will increase the treatment-dependant miscarriage ratein assisted reproduction procedures. A significantly higher impact is shown for one previous miscarriage achieved by assistedreproduction procedures compared with spontaneous conception. Partner change is shown to have no specific impact on thetreatment dependant miscarriage rate, whereas a statistically significant increase in miscarriages in all assisted reproductionprocedures was found among women older than 34 years of age. Overall, the highest rate of treatment-dependant miscarriageswas seen in assisted reproduction procedures with cryopreserved embryo transfer.
Keywords: IVF outcome, IVF registry, miscarriages, previous conception, reproductive history
al., 1996). Using population-based data of 65,751 assistedreproduction treatments (fresh, non-donor eggs or embryos) Infertile women who have experience spontaneous single or performed in the United States in 2000, a miscarriage rate of recurrent abortion will sustain emotional stress (Engelhard et 14.9% per clinical pregnancy and 5.3% per retrieval was al., 2001). Counselling of subfertile couples should therefore reported (Assisted Reproductive Technology Success Rates, include accurate information about the risk of miscarriage adapted to an individual’s reproductive history.
Numerous studies have investigated the wide range of The frequency of loss of clinically recognized pregnancies is aetiology in miscarriages. Women’s age (Abdalla et al., 1993), reported to be 10% (Gilmore and McNay, 1985). The rate of morphological abnormalities of the uterus (Homer et al., early pregnancy loss following assisted reproduction 2000), infection of the reproductive tract (Byrn and Gibson, procedures is thought to be in the range of 18–34% (Bulletti et 1986), maternal endocrine disorders such as luteal phase Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. insufficiency, polycystic ovary syndrome (PCOS), thyroid pharmaceutical agents for controlled ovarian hyperstimulation dysfunction, diabetes mellitus or hyperprolactinaemia (Felberbaum and Dahncke, 2000). Starting with paper (Roberts and Murphy, 2000), ovarian hyperstimulation (Raziel questionnaires, data collection was computerized in 1990 and et al., 2002), and genetic disorders (Zheng et al., 2000) have all IVF units use a nearly uniform software solution. This tool is undergoing further development and will be adapted to theguidelines recommended by the International Working Group It has been demonstrated that in patients with elevated basal for Registers on Assisted Reproduction (IWGRAR) under the FSH concentrations >10 IU/l, half of the pregnancies achieved umbrella of the International Federation of Fertility Societies by IVF treatment ended in a miscarriage (Cédrin-Durnerin et (IFFS) once clearance will be given by WHO (Adamson et al., al., 2003). In addition, a high follicular LH concentration was 2001). Prospectivity of entered records (with a maximum of 8 related to high miscarriage rates in IVF cycles involving days after beginning of ovarian stimulation) was established in clomiphene citrate/gonadotrophin/cetrorelix stimulation 1997. Participation became compulsory in 1999.
Compared with the IVF registries of other countries, the Immunologically mediated abortions (IMA) represent a German registry data contains more information on distinct entity in research. Relations to antiphospholipid reproductive history (Kupka et al., 2003). The dataset of the antibodies, antinuclear antibodies, antithyroid antibodies, American Society for Assisted Reproductive Technology natural killer cells and histocompatibility complex have been (SART), operational since 1985, documents the number of described (Kaider et al., 1999; Ghazeeri and Kutteh, 2001).
previous pregnancies, full-term births (≥37 weeks), preterm Some studies have also explored the effect of obesity births (<37 weeks), spontaneous abortions, and surgical (Fedorcsak et al., 2000), endometriosis (Matorras et al., 1998) sterilizations (Assisted Reproductive Technology Success and psychological factors (Bergant et al., 1997) in spontaneous Rates, 2001). The British Human Fertilization and abortion. Corresponding to aetiology diversity, various Embryology Authority, established in 1991, collects data about treatment strategies have been developed. The efficacy of patient’s previous obstetric history including the total number heparin and low-dose aspirin in women with antiphospholipid of previous pregnancies (natural and assisted conceptions), the syndrome could be shown in different controlled total number of IVF pregnancies, the total number of live investigations (Lee and Silver, 2000). The successful use of births, and the year of the last pregnancy (HFEA, 2000). The metformin to reduce miscarriage rate in PCOS has been annual reports of the French national IVF registry (established demonstrated by Jakubowicz (Jakubowicz et al., 2002). The in 1986) also provide only limited information about possible connection between miscarriage and ovarian reproductive history (FIVNAT, 2000). The records of the stimulation has been demonstrated in a mouse model by German IVF Registry include data of all previous pregnancies Ertzeid (Ertzeid and Storeng 2001). A prominent area of with information about the year, live births, miscarriages, current research concerns preimplantation genetic diagnosis induced abortions, ectopic pregnancies, change of partnership (PGD) during assisted reproduction procedures (Pellicer et al., and use of assisted medical procreation (DIR, 2000).
Information on whether the male partner has ever made awoman pregnant is not reported to the registry. Protection of The aim of the present study was to analyse the impact of privacy in health related registries is required by public previous miscarriages on the outcome of different assisted authorities. Therefore, multiple cycles for a single patient are reproduction procedures including IVF, intracytoplasmatic not linked and identification of single patients can only be sperm injection (ICSI), a combination of both treatments integrated with technical expense using unique algorithms.
(IVF/ICSI) and cryopreserved embryo transfer (CPE) using Similar to other IVF data collections this should be realized population-based data of the German IVF Registry (DIR).
soon as well as using modern techniques like the Internet(Cohen, 2001). Annual reports of the four registries are already National registries in reproductive medicine help reveal trends and correlations (de Mouzon et al., 1993). However, analyticalstudies have to be estimated as representations of special environments of each country, such as legislative restrictions,attitude of insurers and quality of data collection (Lancaster, The records of 174,909 assisted reproduction treatment procedures including IVF, ICSI, a combination of IVF andICSI in one cycle (IVF/ICSI), and CPE were analysed. Gamete The German Embryo Protection Act (EschG, 1990) and intra-Fallopian transfer (GIFT) was performed in 93 cycles guidelines of the German Medical Association, for example, only and therefore excluded from the analysis. In addition, prohibit any kind of donor programmes in IVF procedures, intrauterine insemination (IUI) could not be incorporated restrict the maximum number of transferred embryos to three, because data on this procedure are not collected by the German and effectively prevent embryo selection through only IVF Registry. A total of 103,939 previous pregnancies allowing the freezing of fertilized oocytes in the pronuclear (including live births, miscarriages, induced abortions and ectopic pregnancies) were reported. Previous assistedreproduction procedures could include IUI, IVF, ICSI, These factors have to be considered when comparing results IVF/ICSI, GIFT and CPE without exact specification.
with those derived from other national data collections. The Treatments were performed during January 1998 to December German registry was founded in 1982 and has expanded at 2000. The present analysis was approved by the Board of the various times to include the implementation of new therapeutic Registry. Identifiable information on patient and IVF centre strategies such as micromanipulation, assisted hatching, and Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. A maximum of 103 reproductive centres reported their data, (1.6%). Cycles involving cryopreserved embryo transfer most working as private sector units. Thirty-six are tertiary (CPE, n = 27,021, 15.4%) are reported as a separate category care centres or university hospitals. To evaluate the impact of (Table 2).
previous miscarriages on the outcome of assisted reproductionprocedures, the present study assessed correlations of women’s The average age of the women was 34 years (SD 4.5, range age, previous infertility treatments, change of partnership in 17–46). The average duration of infertility was 5 years (SD previous conceptions and infertility diagnoses. The primary 3.4, range 0–17). Primary infertility was reported in 65% of outcome measure was the miscarriage rate per clinical the cycles and ranged from 58% of the IVF group to 73% in the ICSI treatment group. Infertility diagnoses were classifiedin five groups: tubal disease, male factor, ovulatory disorder, According to the registry guidelines, a miscarriage is defined unexplained infertility and other reasons. The latter category as the loss of a clinically recognized pregnancy during the first included multiple diagnoses as well as severe endometriosis, 24 weeks of gestation. Stillbirths are included in this definition, but induced abortions are reported separately. Amultiple pregnancy ending in a miscarriage is listed as one Of 174,909 started cycles, a total of 161,430 (92%) resulted in miscarriage. According to the registry definition a clinical oocyte retrieval respectively in vital thawed embryos in CPE pregnancy is fixed as the occurrence of at least one cycles. Cycles with follicular puncture where no oocytes could ultrasonography confirmed gestational sac (which excludes be found and cycles with thawing cryopreserved fertilized biochemical pregnancies) with or without confirmation of oocytes where no vital embryos were found were observed in positive heartbeats, as well as ectopic pregnancies and a 8%. A total of 145,807 (83%) cycles resulted in embryo pregnancy loss up to a gestational age of 24 weeks. A live birth transfer. The overall cancellation rate was 8%. Cycles with no is described as a treatment cycle that results in at least one live regular fertilization were seen in 11%. A total of 35,648 born neonate with a minimum gestational age of 25 weeks.
clinical pregnancies were reported, with an overall clinical Multiple live births followed the same definition.
pregnancy rate per transfer of 25%. IVF and ICSI yieldedsimilar pregnancy rates (26%), while combination of both A relatively high percentage of pregnancies were lost of methods yielded a slightly lower rate (25%). Transfer of follow-up (14.2%). From a total of 178,608 records in the cryopreserved embryos result in a 16% clinical pregnancy rate.
dataset, 3699 incomplete records (2.1%) had to be removed Multiple pregnancy was observed in 7930 cycles (22%). A before starting the analysis. Information about luteal phase total of 21,335 live births were reported, for an overall rate per support, body weight, the quality and number of embryos or transfer of 15%. Due to a relatively high miscarriage rate, the previous specific treatments in cases of recurrent miscarriages live birth rate in cycles with cryopreserved embryo transfer only amounted to 9%. Ectopic pregnancies were observed in3% of all procedures.
Logistic regression was used to model success (defined as aclinical pregnancy) as a binomial dependent variable Compared with other registries, the overall miscarriage-rate (McCullagh et al., 1989). Independent variables in the was relatively high (23%). The reported 8311 miscarriages regression models include number of previous miscarriages, include 233 stillbirths. Overall, the highest miscarriage rate duration of infertility, woman’s age, clinical pregnancy rate per was observed in the group of procedures with transfer of retrieval and type of assisted reproduction-procedure, all cryopreserved embryos (27%), and was similar in both ICSI defined as categorical. In models evaluating the impact of the cycles and IVF cycles (23%). Overall, the miscarriage rates number of previous miscarriages, the reference group was per retrieval ranged from 4.0% in the group of CPE to 5.7% in represented by patients without previous miscarriages. In models evaluating the impact of different kinds of assistedreproduction procedure, the reference group was represented A total of 103,939 previous pregnancies were reported. On by patients undergoing IVF procedures. Odds ratio (OR) average, 0.59 (range 0–12, SD 0.98) previous pregnancies per comparing each category of the independent variables to the procedure were listed. The largest group represented 41,082 reference group, and their 95% confidence interval (CI) were live births (40%). A total of 34,281 miscarriages were obtained from the regression coefficient estimates and their registered (33%); ectopic pregnancies were seen in 17,725 standard errors. Wald’s Chi-Square (χ2) test was used to test cases (17%) and induced abortions in 10,851 cases (10%). The the null hypothesis of no association (i.e. OR = 1), whereas the number of previous miscarriages ranged from 1 to 12 (mean precision of the estimates was evaluated using the 95% 0.19, SD 0.52). In 18,808 cycles, one previous miscarriage was confidence interval. For categorical data, e.g. age, the reported, in 3689 cycles two previous miscarriages were Cochran–Mantel–Haenszel statistics with 1 degree of freedom notified and three previous miscarriages were seen in 939 was used. Goodness of fit was indicated by scaled deviance cycles. A total number of 107 cycles (0.4% of all cycles with and Pearson χ2 values (Table 1). The Statistical Analysis
history of pregnancy loss) reported more than three previous System (SAS) version 8.02 (SAS Institute Inc.®, Cary, NC, miscarriages and were not considered in further analyses to The present study focused on 29,003 reported previousmiscarriages, where an embryo transfer in the subsequent Most of the assisted reproduction procedures were planned as assisted reproduction procedure had been performed. In some IVF (n = 75,024, 43%) or ICSI cycles (n = 70,335, 40%). A correlations, only consecutive previous miscarriages were combination (IVF/ICSI) was performed in 2529 procedures Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. Table 1. Goodness of fit.
previous miscarriagesInfluence of women’s age conception (spontaneous/assisted reproduction)Influence of change Table 2. Infertility diagnosis, pregnancy rate and clinical outcome.
Clinical pregnancy rate per retrieval (%) Rate of ectopic pregnancy per retrieval (%) Miscarriage rate per clinical pregnancy (%) Clinical pregnancies with loss of follow-up aValues are means with standard deviation in parentheses.
bVital thawed fertilized oocytes in pronuclear stage.
c0.3% heterotopic pregnancies were reported (118/35.673) in 0,2% of assisted reproduction procedures a live birth and additional extrauterine gravidity was reported (39/21,349).
CPE = cryopreserved embryo transfer.
Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. To answer the question how the number of previous number of previous miscarriages. The live birth rate decreased miscarriages could influence assisted reproduction outcome, a from 13% in patients without a previous miscarriage to 10% in logistic regression model including assisted reproduction patients with three previous miscarriages. The miscarriage rate procedures, miscarriage rates per retrieval and number of per clinical pregnancy increased from 21 to 31%. The live previous miscarriages was established (Table 3). The
birth rate decreased from 13% in patients without any previous reference group comprised patients without previous miscarriage, to 10% in the group of patients with three miscarriages. A highly significant impact could be seen for one, two and three previous miscarriages on all four evaluatedkinds of assisted reproduction procedures (IVF, ICSI, Women’s age is a well-known prognostic factor in human IVF/ICSI, CPE). In ICSI treatments, the miscarriages rates reproduction. To demonstrate the correlation to previous increased from 22% among patients without previous miscarriages, 10 age categories were used (≤26, 27–28, 29–30, miscarriages to 39% for patients with three previous 31–32, 33–34, 35–36, 37–38, 39–40, 41–42, ≥43). The miscarriages. The combination of IVF and ICSI showed an percentages of women with no previous miscarriage declined even higher increase. In general, a positive impact on the from 92% among those less than 27 years of age to 72% miscarriage rate could be observed comparing women with among women 43 years or older. One previous miscarriage primary (no previous pregnancy) and secondary infertility.
was observed only in 7% in the youngest age category with anincrease to 21% in the group of women older than 42 years.
To evaluate the influence of previous miscarriages on the The same increase could be shown for two and three previous outcome of assisted reproduction procedures in general, miscarriages. To analyse the relation of women’s age to the 68,703 IVF cycles were analysed (Table 4). Clinical
miscarriage rate in assisted reproduction procedures in more pregnancy rates and miscarriage rates were associated with the detail, a logistic regression model including assisted Table 3. Previous pregnancies and miscarriage-rate per clinical pregnancy in assisted reproduction procedures.
aPercentages refer to the clinical pregnancy rate per retrieval.
bNo previous pregnancy (primary infertility).
cAt least one previous pregnancy (secondary infertility).
dNo previous miscarriage but potentially previous pregnancies with different outcome.
Table 4. Previous miscarriages and assisted reproduction outcome in IVF procedures.
aNo previous pregnancy (not included in Cochran–Mantel–Haenszel statistics).
bNo previous miscarriage but potentially previous pregnancies with different outcome.
cCochran–Mantel–Haenszel statistics.
ePercentages refer to the sum of each column.
Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. reproduction procedures, miscarriage rates per clinical To answer the question of whether the assisted reproduction pregnancy and age categories was established (Table 5). The
miscarriage rate would differ between patients with previous reference group was represented by patients younger than 27 miscarriages achieved by assisted reproduction treatments or years undergoing IVF procedures. A highly statistically by spontaneous conception, a regression analysis performed, significant correlation was observed for women 35 years or including assisted reproduction procedures, miscarriage rate per clinical pregnancy, and previous consecutive miscarriages
(Table 6). The most important finding was that one previous
To analyse the correlation of infertility diagnoses and miscarriage resulting from an assisted reproduction treatment miscarriage rate in assisted reproduction procedures, a logistic (IVF, ICSI, IVF/ICSI, CPE or IUI) increased the miscarriage regression model including miscarriage rates per retrieval, rate of an ongoing assisted reproduction procedure for all infertility diagnoses and number of previous pregnancies was kinds of treatment relative to the rates where a previous established. The reference group comprised patients with no miscarriage was achieved by spontaneous conception. In IVF previous miscarriage. A statistically significant association to cycles, the rate increased from 26 to 31% and in cycles where the number of previous miscarriages could be found. The a combination of IVF and ICSI was performed, the difference groups of cycles with one (OR 1.375, CI 1.238–1.526, was even larger (27 versus 35%). No statistically significant P<0.001), two (OR 1.288, CI 1.037–1.600, P = 0.0221) and difference could be shown for two or three previous three (OR 1.651, CI 1.093–2.495, P = 0.0173) previous miscarriages demonstrated increased rates in all diagnosiscategories.
Table 5. Women’s age and miscarriage rate per clinical pregnancy in assisted reproduction procedures.
Table 6. Previous consecutive miscarriages achieved by spontaneous conception/assisted reproduction and
miscarriage-rate per clinical pregnancy in assisted reproduction procedures.
aMiscarriages after spontaneous conception.
bMiscarriages after assisted reproduction procedure (IVF, ICSI, IVF/ICSI, CPE, IUI).
Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. To evaluate the impact of a change in partnership on previous Stolwijk described a significant difference in the cumulative consecutive miscarriages, a similar regression model was probability to achieve an ongoing pregnancy in IVF/ICSI performed (Table 7). The reference group was the group of
cycles in the first attempt comparing women with primary and patients with previous miscarriages in the same partnership.
secondary infertility (16 versus 23%) (Stolwijk et al., 2000).
No statistically significant difference could be shown for one, This also could be seen in the present study. The clinical two or three previous consecutive miscarriages.
pregnancy rate in IVF cycles increased from 22% in patientswith primary infertility to 23% in patients with one previous miscarriage (P = 0.0192). Nevertheless, in cycles with morethan one miscarriage, the pregnancy rate decreased to 20%.
Various prognostic factors in assisted reproduction procedureshave been described, such as women’s age (Templeton et al., A previous successful IVF cycle was described as a positive 1996), infertility aetiology (Tan et al., 1992), previous successful prognostic factor for a following attempt (Simon et al., 1993; treatment cycles (Simon, 1993), semen quality parameters Templeton et al., 1996). Unfortunately, this seemed to be (Sukcharoen et al., 1996), embryo quality and number of associated with a higher miscarriage rate, as seen in the current embryos (Scott et al., 1991). It could be demonstrated that in poor responder cycles, the miscarriage rate was 17% (Ulug et al.,2003). Unfortunately, the quality and number of embryos was not The impact of women’s age in assisted reproduction procedures has been evaluated in several studies. Hughesfound women’s age to be a more important factor than semen The present study has examined the relationship between quality, embryo quality and previous response to stimulation in previous miscarriages and the loss of clinically recognized IVF treatments (Hughes et al., 1989). Similar to the present pregnancies in assisted reproduction procedures. Previous findings, Dicker described an increase in miscarriages in IVF research has indicated that miscarriage rates are higher in treatments from 28% in women aged 25 years or younger to pregnancies achieved by assisted reproduction, although the 50% in women 40 years or older (Dicker et al., 1991). The reasons for that observation are not yet completely understood present study demonstrated a statistically significant increase (Ezra and Schenker, 1995). The overall miscarriage rate in the in miscarriages in all assisted reproduction procedures in present study (23%) was relatively high compared with other data. This rate is influenced in part by the relatively high rate ofcycles lost to follow-up. The Danish IVF Registry reported for To evaluate the impact of age concerning uterine and ovarian the years 1994 and 1995 a miscarriage rate per clinical pregnancy factors, Abdalla demonstrated that in cycles with oocyte of 17% in IVF cycles and in 25% of ICSI cycles (Westergaard et donation, women aged 40 years or older will benefit al., 2000). Coulam described a miscarriage rate in IVF cycles of significantly (Abdalla et al., 1993). He described a miscarriage 17% (Coulam et al., 1998). The Israeli Registry reported an rate of 58% in non-donor treatments among women older than overall miscarriage rate of 24% for the period 1995 and 1996 40 years. This was similar to the present findings (Figure 1).
(Insler et al., 2000). The British registry reported a miscarriagerate per clinical pregnancy in IVF and CPE cycles of 13% in the The impact of infertility diagnosis on miscarriage rate was period of April 1998 to March 1999 (HFEA, 2000).
analysed by Tan, using a collective of 700 pregnanciesachieved by IVF therapy (Tan et al., 1992). He described the In this study, the overall miscarriage rate ranged from 21 to highest miscarriage rate in women with unexplained cause of 27%, with the highest range in patients undergoing infertility (36%) followed by tubal damage (34%) and male frozen–thawed embryo transfer. This could be affected by the factor (32%). Miscarriage rates in the present investigation procedure of freezing and thawing itself, but also by the were lower in general, with the highest percentage seen in selection process on day 1 after follicular puncture. According to women suffering from tubal damage and unexplained causes the German embryo protection law, freezing is only allowed of infertility. Infertility diagnosis showed a specific relation to until this day. Fertilized oocytes in the pronuclear stage of lower the number of previous miscarriages in the present study.
quality will be selected for freezing. This could also affect the Kiefer reported a 40% increase in spontaneous abortions in pregnancy rate and consequently the abortion rate.
ICSI cycles with severe oligoasthenozoospermia, but thisfinding was based on a relatively small group of patients (6/15) It was found that having a previous miscarriage increases the (Kiefer et al., 1997). In the current investigation, the overall treatment dependant miscarriage rate in all analysed assisted miscarriage rates in ICSI cycles amounted only 23.0% and reproduction procedures. Similar findings have also been only a small increase was seen compared with IVF cycles described by other researchers (Tatham et al. 2001).
A significantly higher impact was shown for one previous IVF as a therapeutic approach in women experiencing miscarriage resulting from assisted reproduction procedures recurrent miscarriages is a controversial topic. Balasch found compared with a previous miscarriage resulting from that in a group of 12 couples suffering from recurrent spontaneous conception. Bates described a positive effect of one pregnancy loss, all achieved pregnancies after IVF treatment previous early pregnancy loss in IVF cycles (Bates et al., 2002).
ended in a live birth (Balasch et al., 1996). Raziel reported no This finding could not be seen in the present study, since it was decrease of miscarriage rates after IVF treatment in 14 couples not possible to differentiate between previous assisted (Raziel et al., 1997). In the present investigation, a higher reproduction procedures because cycles of individual couples clinical pregnancy rate in IVF treatments was observed inwomen experiencing one previous miscarriage. No benefit was are not linked. A new software solution for data collection willhelp to solve this problem in the future.
observed in reproductive histories with more than one previous Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. Table 7. Previous consecutive miscarriages in the same/different partnership and miscarriage rate in
assisted reproduction.
Dr M. Macaluso, Chief of the Women’s Health and FertilityBranch, Division of Reproductive Health, National Centre forChronic Disease Prevention and Health Promotion(NCCDPHP), Centres for Disease Control and Prevention(CDC), Atlanta, GA helped to establish statistic models andsupervised the project.
Figure 1. Women’s age correlated to clinical pregnancy rate
(•) live birth rate (♦) miscarriage rate per retrieval (×) and
Abdalla HI, Burton G, Kirkland A et al. 1993 Age, pregnancy and miscarriage rate per clinical pregnancy (s ) in IVF miscarriage: uterine versus ovarian factors. Human Reproduction 8, 1512–1517.
Adamson GD, Lancaster P, de Mouzon J et al. F 2001 A simple headstone or just eliminate the chads? Fertility and Sterility 76,
1284–1285.
miscarriage. The live birth rate was negative correlated and the Assisted Reproductive Technology Success Rates 2000 Centers for miscarriage rate positively related to the amount of previous Disease Control and Prevention, American Society for Reproductive Medicine, Society of Assisted ReproductiveTechnology,Resolve. Centers for Disease Control and Prevention, Only limited information is available about the impact of Atlanta 2002, http://www.cdc.gov/nccdphp/drh/assisted change in partnership and miscarriage rates in assisted reproduction procedures. Although this investigation could not Balasch J, Creus M, Fabregues F et al. 1996 In-vitro fertilization treatment for unexplained recurrent abortion: a pilot study.
demonstrate any specific correlation, it would have been Human Reproduction 11, 1579–1582.
expected that the treatment dependant miscarriage rate in Bates GW, Ginsburg ES 2002 Early pregnancy loss in in vitro women with previous miscarriages in a different partnership fertilization (IVF) is a positive predictor of subsequent IVF would be affected (Carp et al., 1994; Stricker et al., 2000).
success. Fertility and Sterility 77, 337–341.
Bergant AM, Reinstadler K, Moncayo HE et al. 1997 Spontaneous Counselling of subfertile couples should include information abortion and psychosomatics. A prospective study on the impact about both the age dependant likelihood of treatment of psychological factors as a cause for recurrent spontaneous dependant miscarriages and the relation to previous pregnancy abortion. Human Reproduction 12, 1106–1110.
Bulletti C, Flamigni C, Giacomucci E 1996 Reproductive failure due to spontaneous abortion and recurrent miscarriage. Human
Reproduction Update 2, 118–136.
The major findings of this study are that any previous Byrn FW, Gibson M 1986 Infectious causes of recurrent pregnancy miscarriage will increase the treatment dependant miscarriage loss. Clinical Obstetrics and Gynecology 29, 925–940.
rate in assisted reproduction procedures. A significantly higher Carp HJ, Toder V, Mashiach S et al. 1994 Effect of paternal impact is shown for one previous miscarriage achieved by leukocyte immunization on implantation after biochemical assisted reproduction procedures compared with spontaneous pregnancies and repeated failure of embryo transfer. American
Journal of Reproductive Immunology 31, 112–115.
conception. Partner change is shown to have no specific Cédrin-Durnerin I, Bstandig B, Galey J, et al. 2003 Beneficial effects impact on the treatment dependant miscarriage rate, whereas a of GnRH agonist administration prior to ovarian stimulation for statistically significant increase in miscarriages in all assisted patients with a short follicular phase. Reproductive BioMedicine reproduction procedures was found among women older than Online 7, 179–184.
34 years of age. Overall, the highest rate of treatment Cohen J 2001 The future of international registries for assisted dependant miscarriages was seen in assisted reproduction reproductive technologies. Fertility and Sterility 76, 871–873.
procedures with cryopreserved embryo transfer.
Coulam CB, Chapman C, Rinehart JS 1998 What is a preclinical pregnancy loss? Journal of Assisted Reproduction and Genetics Article - Effect of miscarriage on subsequent IVF and ICSI pregnancies - MS Kupka et al. 15, 184–187.
Pellicer A, Rubio C, Vidal F et al. 1999 In vitro fertilization plus de Mouzon J, Bachelot A, Spira A 1993 Establishing a national in preimplantation genetic diagnosis in patients with recurrent vitro fertilization registry: methodological problems and analysis miscarriage: an analysis of chromosome abnormalities in human of success rates. Statistics in Medicine 12, 39–50.
preimplantation embryos. Fertility and Sterility 71, 1033–1039.
Dicker D, Goldman JA, Ashkenazi J et al. 1991 Age and pregnancy Raziel A, Friedler S, Schachter M et al. 2002 Increased early rates in in vitro fertilization. Journal of In Vitro Fertilization and pregnancy loss in IVF patients with severe ovarian Embryo Transfer 8, 141–144.
hyperstimulation syndrome. Human Reproduction 17, 107–110.
DIR–Deutsches IVF-Register 2001 Jahrbuch, Bundesgeschaeftsstelle Raziel A, Herman A, Strassburger D et al. 1997 The outcome of in Ärztekammer Schleswig-Holstein, Bad-Segeberg, Germany, vitro fertilization in unexplained habitual aborters concurrent with http://www.deutsches-ivf-register.org.
secondary infertility. Fertility and Sterility 67, 88–92.
Engelhard IM, van den Hout MA, Arntz A 2001 Posttraumatic stress Roberts CP, Murphy AA 2000 Endocrinopathies associated with disorder after pregnancy loss. General Hospital Psychiatry 23,
recurrent pregnancy loss. Seminars in Reproductive Medicine 18,
Ertzeid G, Storeng R 2001 The impact of ovarian stimulation on Scott RT, Hofmann GE, Veeck LL et al. 1991 Embryo quality and implantation and fetal development in mice. Human pregnancy rates in patients attempting pregnancy through in vitro Reproduction 16, 221–225
fertilization. Fertility and Sterility 55, 426–428.
EschG–Gesetz zum Schutz von Embryonen BGBl 1990 1: 2746.
Simon A, Ronit C, Lewin A et al. 1993 Conception rate after in vitro http://www.bmgesundheit.de/rechts/genfpm/embryo/embryo.htm.
fertilization in patients who conceived in a previous cycle.
Ezra Y, Schenker JG 1995 Abortion rate in assisted reproduction – Fertility and Sterility 59, 343–347.
true increase. Early Pregnancy 1, 171–175.
Stolwijk AM, Wetzels AM, Braat DD 2000 Cumulative probability of Fedorcsak P, Storeng R, Dale PO et al. 2000 Obesity is a risk factor achieving an ongoing pregnancy after in-vitro fertilization and for early pregnancy loss after IVF or ICSI. Acta Obstetricia et intracytoplasmic sperm injection according to a woman’s age, Gynecologica Scandinavica 79, 43–48.
subfertility diagnosis and primary or secondary subfertility.
Felberbaum R, Dahncke W 2000 The German IVF Registry as a Human Reproduction 15, 203–209.
quality assurance tool and for use in patient counseling.
Stricker RB, Steinleitner A, Bookoff CN et al. 2000 Successful Gynäkologe 33, 800–811.
treatment of immunologic abortion with low-dose intravenous FIVNAT 2000 Annual Report. French National Register on In Vitro immunoglobulin. Fertility and Sterility 73, 536–540.
Fertilization. http://perso.wanadoo.fr/fivnat.fr/bilan2000.htm.
Sukcharoen N, Keith J, Irvine DS et al. 1996 Prediction of the in- Ghazeeri GS, Kutteh WH 2001 Immunological testing and treatment vitro fertilization (IVF) potential of human spermatozoa using in reproduction: frequency assessment of practice patterns at sperm function tests: the effect of the delay between testing and assisted reproduction clinics in the USA and Australia. Human IVF. Human Reproduction 11, 1030–1034.
Reproduction 16, 2130–2135.
Tan SL, Royston P, Campbell S et al. 1992 Cumulative conception Gilmore DH, McNay MB 1985 Spontaneous fetal loss rate in early and live birth rates after in-vitro fertilisation. Lancet, 339,
pregnancy. Lancet 12, 107.
Human Fertilisation and Embryology Authority (HFEA) 2000 Tatham LM, Schieve L, Jeng G 2001 Spontaneous abortion and Annual Report. http://www.hfea.gov.uk/frame3.htm.
assisted reproductive technology in the United States. Paediatric Homer HA, Li TC, Cooke ID 2000 The septate uterus: a review of and Perinatal Epidemiology 15, A33.
management and reproductive outcome. Fertility and Sterility 73,
Tavaniotou A, Albano C, Van Steirteghem A et al. 2003 The impact of LH serum concentration on the clinical outcome of IVF cycles Hughes EG, King C, Wood EC 1989 A prospective study of in patients receiving two regimens of clomiphene prognostic factors in in vitro fertilization and embryo transfer.
citrate/gonadotrophin/0.25 mg cetrorelix. Reproductive Fertility and Sterility 51, 838–844.
BioMedicine Online 6, 421–426.
Insler V, Gonnen O, Levran D et al. 2000 Assisted reproductive Templeton A, Morris JK, Parslow W 1996 Factors that affect technologies reported in the National Registry of Israel outcome of in-vitro fertilisation treatment. Lancet 348,
1995–1996. Harefuah 139, 421–424.
Jakubowicz DJ, Iuorno MJ, Jakubowicz S et al. 2002 Effects of Ulug U, Ben-Shlomo I, Turan E et al. 2003 Conception rates metformin on early pregnancy loss in the polycystic ovary following assisted reproduction in poor responder patients: a syndrome. Journal of Clinical Endocrinology and Metabolism 87,
retrospective study in 300 consecutive cycles. Reproductive BioMedicine Online 6, 439–443.
Kaider AS, Kaider BD, Janowicz PB et al. 1999 Immunodiagnostic Westergaard HB, Johansen AM, Erb K et al. 2000 Danish National evaluation in women with reproductive failure. American Journal IVF Registry 1994 and 1995. Treatment, pregnancy outcome and of Reproductive Immunology 42, 335–346.
complications during pregnancy. Acta Obstetricia et Kiefer D, Check JH, Katsoff D 1997 Evidence that Gynecologica Scandinavica 79, 384–390.
oligoasthenozoospermia may be an etiologic factor for Zheng CJ, Guo SW, Byers B 2000 Modeling the maternal-age spontaneous abortion after in vitro fertilization-embryo transfer.
dependency of reproductive failure and genetic fitness. Evolution Fertility and Sterility 68, 545–548.
and Development 2, 203–207.
Kupka MS, Dorn C, Richter O et al. 2003 Impact of reproductive history on in vitro fertilization and intracytoplasmatic sperm Received 17 November 2003; refereed 10 December 2003; injection outcome: Evidence from the German IVF Registry.
Fertility and Sterility 80, 508–516.
Lancaster PA 1996 Registers of in-vitro fertilization and assisted conception. Human Reproduction Supplement 11, 89–104.
Lee RM, Silver RM 2000 Recurrent pregnancy loss: summary and clinical recommendations. Seminars in Reproductive Medicine
18,433–440.
Matorras R, Rodriguez F, Gutierrez de Teran G et al. 1998 Endometriosis and spontaneous abortion rate: a cohort study in
infertile women. European Journal of Obstetrics & Gynecology
and Reproductive Biology 77, 101–105.
McCullagh P, Nelder JA 1989 Generalized Linear Models, 2nd edn.

Source: http://dr-kupka.de/miscarriages.pdf