Assisted reproduction technology (ART) is used worldwide, at increasing rates, and data show that some adverse outcomes occur more frequently than following spontaneous conception (SC). Possible ...explanatory factors for the well-known adverse perinatal outcome in ART singletons were evaluated.
PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using donor or frozen oocytes were excluded, as well as those with no control group or including <100 children. The main outcome measure was preterm birth (PTB defined as delivery <37 weeks of gestation), and a random effects model was used for meta-analyses of PTB. Other outcomes were very PTB, low-birthweight (LBW), very LBW, small for gestational age and perinatal mortality.
The search returned 1255 articles and 65 of these met the inclusion criteria. The following were identified as predictors for PTB in singletons: SC in couples with time to pregnancy (TTP) > 1 year versus SC singletons in couples with TTP ≤ 1 year adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50; IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55, 95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine insemination versus SC singletons where TTP ≤ 1 year (AOR 1.45, 95% CI 1.21, 1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95% CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a lower risk of PTB.
Subfertility is a major risk factor for adverse perinatal outcome in ART singletons, however, even in the same mother an ART singleton has a poorer outcome than the non-ART sibling; hence, factors related to the hormone stimulation and/or IVF methods per se also may play a part. Further research is required into mechanisms of epigenetic modification in human embryos and the effects of cryopreservation on this, whether milder ovarian stimulation regimens can improve embryo quality and endometrial conditions, and whether longer culture times for embryos has a negative influence on the perinatal outcome.
Background
Approximately 50 000 oocyte donation (OD) treatment cycles are now performed annually in Europe and the US.
Objectives
To ascertain whether the risk of adverse obstetric and ...perinatal/neonatal outcomes is higher in pregnancies conceived by OD than in pregnancies conceived by conventional in‐vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) or spontaneously.
Search Strategy
A systematic search was performed in the PubMed, Cochrane and Embase databases from 1982–2016. Primary outcomes were hypertensive disorders of pregnancy, pre‐eclampsia (PE), gestational diabetes mellitus, postpartum haemorrhage, caesarean section, preterm birth, low birthweight and small for gestational age.
Selection criteria
Inclusion criteria were original studies including at least five OD pregnancies with a control group of pregnancies conceived by conventional IVF/ICSI or spontaneous conception, and case series with >500 cases reporting one or more of the selected complications. Studies not adjusting for plurality were excluded.
Data collection and analysis
Thirty‐five studies met the inclusion criteria. A random‐effects model was used for the meta‐analyses.
Main results
For OD pregnancies versus conventional IVF/ICSI pregnancies the risk of PE was adjusted odds ratio (AOR) 2.11 (95% CI, 1.42–3.15) in singleton and AOR 3.31 (95% CI, 1.61–6.80) in multiple pregnancies. The risks of preterm birth and low birthweight in singletons were AOR 1.75 (95% CI, 1.39–2.20) and 1.53 (95% CI, 1.16–2.01), respectively.
Conclusions
OD conceptions are associated with adverse obstetric and neonatal outcomes. To avoid the additional increase in risk from multiplicity, single‐embryo transfer should be the choice of option in OD cycles.
Tweetable
Oocyte donation pregnancies have increased risk of a range of obstetric and neonatal complications.
Tweetable
Oocyte donation pregnancies have increased risk of a range of obstetric and neonatal complications.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights14257.
STUDY QUESTION
What is the prevalence in a normal population of polycystic ovary syndrome (PCOS) according to the Rotterdam criteria versus revised criteria including anti-Müllerian hormone (AMH)?
...SUMMARY ANSWER
The prevalence of PCOS was 16.6% according to the Rotterdam criteria. When replacing the criterion for polycystic ovaries by antral follicle count (AFC) > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 and 8.5%, respectively.
WHAT IS KNOWN ALREADY?
The Rotterdam criteria state that two out of the following three criteria should be present in the diagnosis of PCOS: oligo-anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries (AFC ≥ 12 and/or ovarian volume >10 ml). However, with the advances in sonography, the relevance of the AFC threshold in the definition of polycystic ovaries has been challenged, and AMH has been proposed as a marker of polycystic ovaries in PCOS.
STUDY DESIGN, SIZE, DURATION
From 2008 to 2010, a prospective, cross-sectional study was performed including 863 women aged 20–40 years and employed at Copenhagen University Hospital, Rigshospitalet, Denmark.
PARTICIPANTS/MATERIAL, SETTING, METHODS
We studied a subgroup of 447 women with a mean (±SD) age of 33.5 (±4.0) years who were all non-users of hormonal contraception. Data on menstrual cycle disorder and the presence of hirsutism were obtained. On cycle Days 2–5, or on a random day in the case of oligo- or amenorrhoea, sonographic and endocrine parameters were measured.
MAIN RESULTS AND THE ROLE OF CHANCE
The prevalence of PCOS was 16.6% according to the Rotterdam criteria. PCOS prevalence significantly decreased with age from 33.3% in women < 30 years to 14.7% in women aged 30–34 years, and 10.2% in women ≥ 35 years (P < 0.001). In total, 53.5% fulfilled the criterion for polycystic ovaries with a significant age-related decrease from 69.0% in women < 30 years to 55.8% in women aged 30–34 years, and 42.8% in women ≥ 35 years (P < 0.001). AMH or age-adjusted AMH Z-score was found to be a reliable marker of polycystic ovaries in women with PCOS according to the Rotterdam criteria area under the curve (AUC) 0.994; 95% confidence interval (CI): 0.990–0.999 and AUC 0.992 (95% CI: 0.987–0.998), respectively, and an AMH cut-off value of 18 pmol/l and AMH Z-score of −0.2 showed the best compromise between sensitivity (91.8 and 90.4%, respectively) and specificity (98.1 and 97.9%, respectively). In total, AFC > 19 or AMH > 35 occurred in 17.7 and 23.0%, respectively. The occurrence of AFC > 19 or AMH > 35 in the age groups < 30, 30–34 and ≥ 35 years was 31.0 and 35.7%, 18.8 and 21.3%, and 9.6 and 18.7%, respectively. When replacing the Rotterdam criterion for polycystic ovaries by AFC > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 or 8.5%, respectively, and in the age groups < 30, 30–34 and ≥ 35 years, the prevalences were 17.9 and 22.6%, 3.6 and 5.6%, and 3.6 and 4.8%, respectively.
LIMITATIONS, REASON FOR CAUTION
The participants of the study were all health-care workers, which may be a source of selection bias. Furthermore, the exclusion of hormonal contraceptive users from the study population may have biased the results, potentially excluding women with symptoms of PCOS.
WIDER IMPLICATIONS OF THE FINDINGS
AMH may be used as a marker of polycystic ovaries in PCOS. However, future studies are needed to validate AMH threshold levels, and AMH Z-score may be appropriate to adjust for the age-related decline in the AFC.
STUDY FUNDING/COMPETING INTEREST(S)
None.
TRIAL REGISTRATION NUMBER
Not applicable.
STUDY QUESTION
Are singletons born after frozen embryo transfer (FET) at increased risk of being born large for gestational age (LGA) and if so, is this caused by intrinsic maternal factors or ...related to the freezing/thawing procedures?
SUMMARY ANSWER
Singletons after FET have an increased risk of being born LGA. This cannot solely be explained by intrinsic maternal factors as it was also observed in sibling pairs, where the sibling conceived after FET had an increased risk of LGA compared with the sibling born after Fresh embryo transfer.
WHAT IS KNOWN ALREADY
FET singletons have a higher mean birthweight than singletons born after transfer of fresh embryos, and FET singletons may be at an increased risk of being born LGA.
STUDY DESIGN, SIZE, DURATION
The national register–based controlled cohort study involves two populations of FET singletons. The first population (A: total FET cohort) consisted of all FET singletons (n = 896) compared with singletons born after Fresh embryo transfer (Fresh) (n = 9480) and also with that born after natural conception (NC; n = 4510) in Denmark from 1997 to 2006. The second population (B: Sibling FET cohort) included all sibling pairs, where one singleton was born after FET and the consecutive sibling born after Fresh embryo transfer or vice versa from 1994 to 2008 (n = 666). The sibling cohort included n = 550 children with the sibling combination first child Fresh/second child FET and n = 116 children with the combination first child FET/second child Fresh.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Main outcome measures were LGA defined as birthweight of >2 SD from the population mean (z-score >2) according to Marsáls curves. Macrosomia was defined as birthweight of >4500 g. Crude and adjusted odds ratios (AORs) of LGA and macrosomia were calculated for FET versus Fresh and versus NC singletons in the total FET cohort. Similarly, AOR was calculated for FET versus Fresh in the sibling cohort. Adjustments were made for maternal age, parity, child sex, year of birth and birth order in the sibling analyses. Meta-analyses were performed by pooling our data with the previously published cohort studies on LGA and macrosomia.
MAIN RESULTS AND THE ROLE OF CHANCE
The AORs of LGA (z-score >2) and macrosomia in FET singletons versus singletons conceived after Fresh embryo transfer were 1.34 95% confidence interval (95% CI) 0.98–1.80 and 1.91 (95% CI 1.40–2.62), respectively. The corresponding risks for FET versus NC singletons were 1.41 (95% CI 1.01–1.98) for LGA and 1.67 (95% CI 1.18–2.37) for macrosomia. The increased risk of LGA and macrosomia in FET singletons was confirmed in the sibling cohort also after adjustment for birth order. Hence, the increased risk of LGA in FET singletons cannot solely be explained by being the second born or by intrinsic maternal factors, but may also partly be related to freezing/thawing procedures per se. In the meta-analysis, the summary effects of LGA and macrosomia in FET versus singletons conceived after Fresh embryo transfer were AOR 1.54 (95% CI 1.31–1.81) and AOR 1.64 (95% CI 1.26–2.12), respectively. The corresponding figures for FET versus NC singletons were for LGA AOR 1.32 (95% CI 1.07–1.61) and macrosomia AOR 1.41 (95% CI 1.11–1.80), respectively.
LIMITATIONS, REASONS FOR CAUTION
Adjustment for body mass index as a possible confounder was not possible. The size of the FET/Fresh sibling cohort was limited; however, the complete sibling cohort was sufficiently powered to explore the risk of LGA. A bias is very unlikely as data coding was based on national registers.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings are consistent with the previous Nordic studies and thus can be generalized to the Nordic countries. The causes for LGA in FET singletons should be further explored.
STUDY FUNDING/COMPETING INTEREST(S)
No external funding was used for this project. None of the authors have any conflict of interest to declare.
The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the ...European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models.
ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised.
Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements.
This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.
Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low ...bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis.
The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between -2·5 and -4·0 if no previous radiographic vertebral fracture, or between -1·5 and -4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than -4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66).
Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43-40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45-60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40-0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39-0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68-0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42-0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40-0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66-0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95-1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90-1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% 136/8043 vs 1·3% 104/8028, HR 1·32, 1·02-1·70; p=0·034), but not myocardial infarction (0·7% 60/8043 vs 0·9% 74/8028, HR 0·82, 0·58-1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% 401/8043 vs 4·4% 356/8028, 0·98-1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 5·0% of 8043 vs 343 4·3% of 8028, HR 1·17, 1·02-1·36; p=0·029, as did stroke (2·3% 187/8043 vs 1·7% 137/8028, HR 1·37, 1·10-1·71; p=0·0051).
Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis.
Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.
STUDY QUESTION
Does neonatal outcome including congenital malformations in children born after ICSI with epididymal and testicular sperm testicular sperm extraction (TESE)/percutaneous epididymal ...sperm aspiration (PESA)/testicular sperm aspiration (TESA) (TPT) differ from neonatal outcome in children born after ICSI with ejaculated sperm, IVF and natural conception (NC)?
SUMMARY ANSWER
Children born after TPT have similar neonatal outcome, including total malformation rates, as have children born after ICSI and IVF with ejaculated sperm. Testing for variance over the four groups may indicate smaller differences in specific malformation rates with TPT as the highest risk group.
WHAT IS KNOWN ALREADY
Regarding neonatal outcome as well as congenital malformations in children born after TPT, studies are few, with limited sample size, heterogeneous and often performed without relevant control groups.
STUDY DESIGN, SIZE, DURATION
Population-based cohort study including all Danish children born after TPT and fresh embryo transfer in Denmark from 1995 to 2009. Children born after transfer of frozen–thawed embryos were excluded. Control groups of children conceived by ICSI with ejaculated sperm, IVF and NC were identified by cross-linkage of the Danish IVF Register, Medical Birth Register (MBR) and National Hospital Discharge Register (HDR).
PARTICIPANTS/MATERIALS, SETTING
The study group consisted of 466 children born after TPT, while the control groups consisted of 8967 (ICSI with ejaculated sperm), 17 592 (IVF) and 63 854 (NC) children. Neonatal outcomes and congenital malformations were analysed for singletons and twins separately. Risk estimates for low birthweight (LBW, <2500 g) and preterm birth (PTB, <37 gestational weeks) were adjusted for maternal age, parity, child gender and year of childbirth. The study group was identified from the Danish national database on children born after TPT. Control groups were obtained from the IVF register and the MBR. All information included in the study was retrieved from the national registers.
MAIN RESULTS AND THE ROLE OF CHANCE
Considering singletons and twins as one group, the sex ratio (♂/♀) was significantly lower for children born after TPT (0.89) compared with conventional IVF (1.11; P = 0.017) but did not differ significantly when compared with ICSI with ejaculated sperm (0.94) and NC (1.05). The mean birthweight (BW) for singletons did not differ significantly between groups when including only first-born children. The mean gestational age (GA) in the TPT singletons (279 ± 12 days) was significantly higher compared with IVF (276 ± 18 days; P = 0.02), but similar to ICSI with ejaculated sperm and NC singletons when including only first-born children (277 ± 16 days and 279 ± 14 days, respectively). Rate of stillbirths, perinatal and neonatal mortality in the group of TPT singletons did not differ significantly from any of the control groups. Comparable results were found for the TPT twin group, except for perinatal mortality, which was significantly lower in the TPT group compared with naturally conceived twins. The adjusted risk of LBW was significantly higher for TPT versus NC singletons adjusted odds ratio (AOR) = 0.67 (0.48–0.93); however AOR for PTB was similar in the two groups. Regarding twins, similar adjusted risks were observed for PTB and LBW between the TPT and all three control groups. Significantly more Caesarean sections were performed after IVF (27.3% for singletons) and ICSI (25.1% for singletons) with ejaculated sperm compared with the TPT group (16.4% for singletons). The total rate of congenital malformations in the TPT group was 7.7% and did not differ significantly from any of the control groups. However, singleton TPT boys showed an increased rate of cardiac malformations (3.6%) compared with singleton boys after IVF (1.4%; P = 0.04) and NC (1.1%; P = 0.02). Considering the level of male infertility as a continuum over the four groups, tests for variance in the rate of cardiac malformations in singleton boys, and undescended testicles for singleton as well as twin boys were each significantly increased from NC to IVF to ICSI to TPT (P < 0.001). The rate of hypospadias showed the same pattern, but the TPT group did not differ significantly compared with the control groups.
LIMITATIONS, REASONS FOR CAUTION
One of the limitations is that the TPT group could not be classified according to testicular or epididymal sperm, as these data were not available in the IVF register. Another limitation is that registry-based studies are encumbered with the risk of reporting or coding errors or missing data due to insufficient coding. However, the quality of data on congenital malformations in HDR has, in other studies, been validated and found acceptable for epidemiological research, and furthermore, recordings on study and control groups are performed similarly.
WIDER IMPLICATIONS OF THE FINDINGS
Accumulating data show that TPT treatment is equally safe as conventional ICSI and IVF treatment and as NC with regard to neonatal outcome including congenital malformation.
STUDY FUNDING/POTENTIAL COMPETING INTERESTS
This study is supported by Laboratory of Reproductive Biology, Scientific Unit, Horsens Hospital. No competing interests declared.
Abstract
STUDY QUESTION
What are the long-term chances of having a child for couples starting fertility treatments and how many conceive with ART, IUI and without treatment?
SUMMARY ANSWER
Total ...5-year live birthrates were strongly influenced by female age and ranged from 80% in women under 35–26% in women ≥40 years, overall, 14% of couples conceived naturally and one-third of couples starting treatments with intrauterine insemination delivered from that treatment.
WHAT IS KNOWN ALREADY
Few studies report success rates in fertility treatments across a couple's complete fertility treatment history, across clinics, evaluating live births after insemination, ART and natural conceptions.
STUDY DESIGN, SIZE, DURATION
This register-based national cohort study from Denmark includes all women initiating fertility treatments in public and private clinics with homologous gametes in 2007–2010.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women were identified in the Danish ART Registry and were cross-linked with the Medical Birth Registry to identify live births. Subfertile couples were followed 2 years (N = 19 884), 3 years (N = 14 445) and 5 years (N = 5165), or until their first live birth. Cumulative live birthrates were estimated 2, 3 and 5 years from the first treatment cycle, in all women, including drop-outs. Birthrates were stratified by type of first treatment (ART/IUI), mode of conception (ART/IUI/natural conception) and female age.
MAIN RESULTS AND THE ROLE OF CHANCE
Within 5 years, in women aged <35 years (N = 3553), 35–39 years (N = 1156) and ≥40 years (N = 451), a total of 64%, 49% and 16% had a live birth due to treatment, respectively. Additionally, in women aged < 35 years, 35–39 years and ≥40 years, 16%, 11% and 10% delivered after natural conception, yielding total 5-year birthrates of 80%, 60% and 26%. In women starting treatments with IUI (N = 3028), 35% delivered after IUI within 5 years, 24% delivered after shift to ART treatments and 17% delivered after natural conception. Within 5 years from starting treatments with ART (N = 2137), 53% delivered after ART, 11% delivered after natural conception and 0.6% delivered after IUI.
LIMITATIONS, REASONS FOR CAUTION
Birthrates are most likely higher compared to countries without national coverage of treatments and results are influenced by laws and regulations. Information on duration of infertility prior to treatment was not available. Future prospective intervention studies should focus on the role of expectant management.
WIDER IMPLICATIONS OF THE FINDINGS
Our results can provide couples with a comprehensible age-stratified prognosis at start of treatment.
STUDY FUNDING/COMPETING INTEREST(S)
This study was unconditionally funded by Ferring Pharmaceuticals and the Augustinus foundation. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: S.S.M. received an unconditional grant from Ferring Pharmaceuticals; A.A.H. has received personal fees from Ferring Pharmaceuticals not related to this work; A.N.A. reports grants and personal fees from Ferring Pharmaceuticals, personal fees from Merck Serono, grants and personal fees from MSD, outside the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
TRIAL REGISTRATION NUMBER
The study was approved by the Danish Data Protection Agency (J.nr. 2012-41-1330).
Abstract
STUDY QUESTION
Is the number of aspirated oocytes in the first ART cycle associated with the cumulative live birthrates (CLBR) in subsequent cycles?
SUMMARY ANSWER
The number of aspirated ...oocytes in the first cycle was associated with CLBR in subsequent cycles. Previous treatment response predicts outcome in future cycles.
WHAT IS KNOWN ALREADY
Previous reports have shown a positive association between the number of retrieved oocytes and live birthrate per fresh treatment cycle. This has also been shown for the CLBR in one complete ART-cycle, including possible subsequent frozen-thawed transfers (FER). It has been shown that women with less than five oocytes in the first cycle have poorer outcome within six complete cycles than women with more than 12 oocytes, suggesting that the number of aspirated oocytes in the first cycle may be reproduced in later cycles. However, other studies have shown that an initial low treatment response may be improved with increased gonadotrophin start-dose.
STUDY DESIGN, SIZE, DURATION
The Danish National IVF-registry includes all ART treatments in public and private clinics since 1994. Treatment-cycles were cross-linked with the Medical Birth Registry, identifying treatment-related births and natural conception births. This national cohort study includes all women starting ART treatments with homologous eggs between 2002 and 2011, N = 30 486. Subjects were followed for up to four fresh ART-cycles including subsequent FER-cycles (=four complete cycles), until the first livebirth, or until December 2011.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The CLBR within 1-4 complete ART-cycles were calculated as the proportion of women with a livebirth, out of all women initiating ART-treatment, including drop-outs (no livebirth or no continued treatment within follow-up). In women with one year follow-up from last treatment, multivariate logistic regression analysis assessed impact of retrieved oocytes on CLBR, adjusting results for female age and cause of infertility. Hospital admission due to ovarian hyperstimulation syndrome (OHSS) was reported.
MAIN RESULTS AND THE ROLE OF CHANCE
After one, two and three complete ART-cycles, the CLBRs attributable to ART treatment were 26.4% 95%CI 25.9-26.9, 42.6% 42.0-43.1 and 51.3% 50.7-51.9, respectively. The CLBR attributable to non-ART related conception (natural conception or intrauterine insemination) were 5.3% 5.0-5.6, 8.3% 8.0-8.7 and 10.6% 10.3-11.0, after one, two and three complete cycles. In women without a live birth in the first complete cycle, the number of aspirated oocytes predicted the outcome in the second and third cycle: When compared to women with 0-3 aspirated oocytes in the first cycle, the odds for live birth in the second and third cycle was 1.18 1.07-1.30 for women with 4-9 aspirated oocytes in the first cycle, 1.41 1.27-1.57 for women with 10-15 aspirated oocytes and 1.63 1.42-1.88 for women with more than 15 aspirated oocytes. For women without a livebirth in the first and second cycle, the sum of aspirated oocytes predicted outcome in the third complete cycle. Women with a sum larger than six aspirated oocytes, had marked increased odds ratios for livebirth in the third complete cycle, compared to women with a sum of 0-6 oocytes in the first and second fresh cycle. Incidence of hospital-admission due to OHSS was 1.7% in the first cycle, decreasing to 1.3% and 1.0% in the second and third cycles.
LIMITATIONS, REASONS FOR CAUTION
Although mandatory, there may be treatment-cycles not registered in the IVF-registry. Missing information in number of aspirated oocytes are most likely random losses of information. There were few observations in women with more than 15 aspirated oocytes and these birthrates should be interpreted cautiously. Information on gonadotrophin dose used for stimulation was not available, nor was information on dose adjustments in subsequent cycles.
WIDER IMPLICATIONS OF THE FINDINGS
With these results we can counsel couples returning for fertility treatments, providing an age-stratified revised prognosis for chances of live birth and risk of OHSS, reflecting prior failed attempts and previous ovarian response.
STUDY FUNDING/COMPETING INTEREST(S)
This study was unconditionally funded by Ferring Pharmaceuticals and ReproUnion. The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication. The authors have no conflicts of interest.
TRIAL REGISTRATION NUMBER
The study was approved by the Danish Data Protection Agency (J.nr. 2012-41-1330).
During the past two decades, magnetic resonance imaging (MRI) has increasingly been used diagnostically in axial spondyloarthritis (axSpA), and in 2009 MRI was introduced in the Assessment of ...SpondyloArthritis Society (ASAS) classification criteria. In clinical practice, there is a risk of overdiagnosis if MRI findings are not related to clinical and biochemical findings. The aim of this study was to provide an estimate of the prevalence of axSpA in a cohort of clinical patients with low back pain and findings suggestive of axSpA according to ASAS through consensus diagnosis at a multi-disciplinary team (MDT) conference, and to describe the performance of the features included in the ASAS criteria.
Consensus diagnoses of axSpA at MDT conferences were retrospectively established at 3.5 years' follow-up in a cohort of 84 patients, initially referred with disease features according to the ASAS criteria. Patients were examined clinically regarding spondyloarthritis features, and biochemical tests and MRI of the sacroiliac joints and entire spine were performed at baseline and after a mean of 3.5 years.
According to the MDT consensus, 25 patients (30%) of the total cohort had axSpA at follow-up; 40% of individuals who fulfilled the ASAS criteria at baseline had axSpA, and 37% at follow-up; 96% of axSpA patients according to the MDT consensus met the ASAS criteria at baseline and 92% at follow-up.
Approximately one-third of the included patients had axSpA when evaluated at the MDT conference. The ASAS criteria had low predictive value, but high sensitivity at both baseline and follow-up.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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