Si può desiderare di provare un trattamento naturale disfunzione erettile come un diverso per i problemi di costruzione. Al giorno d oggi ci sono diverse terapie sul mercato, ma un trattamento naturale disfunzione erettile è stato confermato qualche ora e ora di nuovo per dare risultati efficienti e permanenti. Cos è la disfunzione sessuale? L incapacità di sviluppare o sostenere una costruzione abbastanza lungo per fare l amore è chiamato disfunzione erettile, ED https://farmacia-senzaricetta.it/ o (maschio) problemi di erezione. Tutti gli uomini possono avere problemi di costruzione di volta in volta e gli scienziati considerano ED essere presenti se si verificano problemi di costruzione almeno il 25% del tempo. Alcuni fatti duri: ED Può essere dovuto a problemi emotivi. Stress, pressione, giltiness, depressione, bassa autostima e ansia prestazioni può essere la causa dei vostri problemi di costruzione. La ricerca ha confermato che il 90 per cento della disfunzione erettile è fisica in origine, non emotiva. L impotenza colpisce la maggior parte degli uomini durante la loro vita e può essere dovuto a troppo colesterolo, problemi cardiaci, diabete, ipertensione, fumo o alcol. Alcuni rimedi possono essere la ragione. Le questioni legate al movimento sono collegate. Se ti occupi dei tuoi problemi di movimento, hai piu possibilita di risolvere questo problema. Qui ci sono 5 consigli facili su come aumentare la circolazione: 1. Mangia i pasti giusti. Questo ti rendera il flusso sanguigno ovvio. Una grande parte di rimanere sani e anche mantenere il flusso sanguigno ovvio è legato al vostro piano di alimentazione quotidiana e quello che si mangia. Una buona cura per la disfunzione erettile è mangiare un piano a basso contenuto di grassi e grande alimentazione di fibre. Mangiare fibre tutti i giorni e questo viene scoperto in prodotti cerealicoli cereali integrali, frutta e verdura. Evitare il più possibile pasti pronti o pasti non sani. 2. Wonder herbal rimedi. Molti rimedi vegetali per ED eseguire bene come possono migliorare il movimento. Hanno molto meno reazioni avverse rispetto ai farmaci convenzionali e si svolgono in modo efficiente per migliorare hardons e la forza, troppo. Erbe naturali come Ginkgo Biloba sono utilizzati come una strategia per ED. Gli specialisti di erboristeria credono anche che le spezie o le erbe come noce moscata, portano al movimento intorno al corpo, tra cui il pene. 3. Vitamine naturali vitali. Gli scienziati sanitari hanno scoperto che una mancanza di supplemento è tipico tra gli uomini con ED in particolare vitamina A. Se si ha una mancanza del nutriente ossido di zinco, Questo è stato confermato per portare alla disfunzione erettile. Queste inadeguatezze derivano dal fatto che molti valori nutrizionali in quello che mangiamo piano non sono sufficienti. Aggiungere al vostro fabbisogno di nutrienti aumenterà la circolazione del sistema e migliorare questa condizione. Gli integratori alimentari sono completamente naturali, quindi non dovrete preoccuparvi dei rischi di reazioni avverse. Inoltre, queste vitamine naturali sono utili per il vostro benessere over-all. Oltre a questi vantaggi benessere, disfunzione erettile vitamine naturali e integratori costano molto meno di farmaci rimedi. 4. Esercitare. Fai una mossa e non un tablet vibrante. Camminare farà di più per migliorare e sostenere hardons di qualsiasi altra compressa chimica nel lungo periodo. Il fitness fisico manterrà bassi livelli di pressione e mantenere grandi stadi di movimento. Andando per un 20-30 minuti di movimento rapido ogni giorno, può affrontare questo problema e può sostenere la vostra libido senza l uso di qualsiasi farmaco. 5. Sottolineare. Questo è il peggior attaccante per problemi di erezione. Scopri diversi metodi per riposare. Alcuni metodi tipici per riposare includono la lettura di un libro, la meditazione, un bagno rilassante o allenamenti di respirazione. Sto solo imparando alcuni semplici allenamenti di respirazione che possono migliorare significativamente il movimento nel reparto pantaloni. Una naturale disfunzione erettile soluzioni di trattamento stanno diventando sempre più popolare con gli uomini. Questi rimedi a base di erbe sono preferiti perché non hanno reazioni avverse e sono confermati essere efficiente come il farmaco. La maggior parte degli uomini combattere parlano dei loro problemi, in particolare la disfunzione erettile come c è poca discussione sui problemi di erezione. La verita e che ED ha un impatto su piu di dieci milioni di uomini solo negli Stati Uniti. Non siete soli e l aiuto è disponibile.
Kupka.info
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 Reproduction8, 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. ReproductiveFertility 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. ReproductiveBioMedicine 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. EvolutionFertility 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.
Anaesthetic Information Sheet for Hernia Surgery Overall philosophy: We aim to provide you with the best and safest anaesthetic care available anywhere. We aim to achieve the best possible pain relief. We aim to do what we can to make your stay in hospital as pleasant as possible. We aim to treat you the way you want to be treated: We do not “do” mediocre. This sheet lists what we do for the
Journal of Dermatology 2010; 37: 708–713Anti-infliximab antibody status and its relation toclinical response in psoriatic patients: A pilot studyEsra ADIS¸EN,1 Arzu ARAL,2 Cemalettin AYBAY,2 Mehmet Ali GUDepartments of 1Dermatology and 2Immunology, Gazi University, Faculty of Medicine, Ankara, TurkeyAlthough the mechanisms underlying the loss of response to infliximab are not completely und