| 1. |
- Einarsson, Snorri, 1973, et al.
(author)
-
No effect of weight intervention on perinatal outcomes in obese women scheduled for in vitro fertilization treatment
- 2019
-
In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 98:6, s. 708-714
-
Journal article (peer-reviewed)abstract
- Introduction Large observational studies have shown that obstetric and perinatal outcomes are negatively affected in obese women. In contrast, a recent Dutch randomized trial of infertile women and lifestyle weight intervention found no difference between the weight intervention group and the control group in obstetric or neonatal outcomes. We have recently published a large Nordic randomized trial where obese women scheduled for in vitro fertilization (IVF) treatment went through an intensive weight intervention treatment before IVF. No significant effect on live birth rate was found, despite large weight loss in the intervention group. The present study was conducted primarily to find out the effect of weight intervention in obese women scheduled for IVF on mean birthweight and mean deviation from expected birthweight, and secondarily the effect on other perinatal and maternal outcomes. Material and methods A secondary analysis of a prospective, randomized controlled trial performed between 2010 and 2016 in the Nordic countries was performed. In all, 317 women were randomized either to weight reduction and IVF treatment (n = 160) or IVF only (n = 157) and the primary end‐point was live birth. From this study, all births were analyzed for perinatal and maternal outcomes. Nine infertility clinics participated, including women < 38 years of age planning for IVF, and having a body mass index ≥ 30 and < 35 kg/m2. Data concerning perinatal and maternal outcomes were gathered from maternal health‐care and delivery records for mother and child. All analyses were performed on singletons only. Results There were 87 live births, 45 singletons in the intervention group and 41 singletons and one twin birth in the control group. The maternal characteristics for the women having a live birth were comparable in the two groups. The primary outcomes, mean birthweight, in the weight intervention and IVF group and the IVF only group were; 3486 g (standard deviation [SD] 523) vs 3584 g (SD 509) (P = 0.46), mean difference −98.6 g (95% confidence interval [CI] −320.3 to 123.2); deviation from expected birthweight 0.25% (SD 10.4) vs 0.87% (SD 12.9), mean difference 1.1% (95% CI −6.1 to 3.9). The estimates of the secondary perinatal and maternal outcomes in the 2 groups were: preterm birth < 37 weeks 2 (4.4%) vs 1 (2.4%) (odds ratio [OR] 1.95; 95% CI 0.17‐22.36), small‐for‐gestational‐age 0 (0%) vs 1 (2.4%), mean gestational age (days) 278 vs 280 (P = 0.95), preeclampsia 5 (11.1%) vs 4 (9.8%) (OR 1.19; 95% CI 0.30‐4.76), cesarean section 13 (28.9%) vs 10 (24.4%) (OR 1.14; 95% CI 0.45‐2.94). Conclusions The outcomes in both groups were generally good. There are no indications that weight intervention in this setting, in infertile women with obesity WHO class 1 undergoing IVF, has a negative impact on mean birthweight and deviation from expected birthweight. However, the data are not sufficiently robust to draw firm conclusions concerning other outcomes.
|
|
| 2. |
- Einarsson, Snorri, 1973, et al.
(author)
-
Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.
- 2017
-
In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 32:8, s. 1621-1630
-
Journal article (peer-reviewed)abstract
- Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women?An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF.Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women.A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included.Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only.In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found.The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2.The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results.The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose.ClinicalTrials.gov number, NCT01566929.23-03-2012.05-10-2010.
|
|
| 3. |
- Kluge, Linda, 1968, et al.
(author)
-
Cumulative live birth rates after weight reduction in obese women scheduled for IVF: follow-up of a randomized controlled trial.
- 2019
-
In: Human reproduction open. - : Oxford University Press (OUP). - 2399-3529. ; 2019:4
-
Journal article (peer-reviewed)abstract
- Did weight reduction in obese women scheduled for IVF increase cumulative live birth rate (CLBR) after 2years?Weight loss prior to IVF did not increase CLBR.Few studies have investigated the effect of weight reduction in obese infertile women scheduled for IVF. In a recent randomized controlled trial (RCT), including one IVF cycle, we found no increase in live birth rate after weight reduction. Weight regain after obesity reduction treatment often occurs, and children born to obese women have a higher risk of childhood obesity.A 2-year follow-up of a multicenter, RCT running between 2012 and 2018 was performed. Out of 317 women randomized to weight reduction followed by IVF treatment or IVF treatment-only, 305 remained in the full analysis set. Of these women, 90.5% (276/305) participated in this study.Nine infertility clinics in Sweden, Denmark and Iceland participated in the RCT. Obese women under 38years of age having a BMI ≥30 and<35kg/m2 were randomized to weight reduction and IVF or IVF-only. In all, 160 patients were randomized to a low calorie diet for 12weeks and 3-5weeks of weight stabilization, before IVF and 157 patients to IVF-only. Two years after randomization, the patients filled in a questionnaire regarding current weight, live births and ongoing pregnancies.42 additional live births were achieved during the follow-up in the weight reduction and IVF group, and 40 additional live births in the IVF-only group, giving a CLBR, the main outcome of this study, of 57.2% (87/152) and 53.6% (82/153), respectively (P=0.56; odds ratio (OR) 1.16, 95% CI: 0.74-1.52). Most of the women in the weight reduction and IVF group had regained their pre-study weight after 2years. The mean weight gain over the 2years was 8.6kg, while women in the IVF-only group had a mean weight loss of 1.2kg. At the 2-year follow-up, the weight standard deviation scores of the children born in the original RCT (index cycle) were 0.218 (1.329) (mean, SD) in the weight reduction and IVF group and-0.055 (1.271) (mean, SD) in the IVF-only group (P=0.25; mean difference between groups, 0.327; 95% CI: -0.272 to 0.932).All data presented in this follow-up study were self-reported by the participants, which could affect the results. A further limitation is in power for the main outcome. The study is a secondary analysis of a large RCT, where the original power calculation was based on live-birth rate after one cycle and not on CLBR.The follow-up indicates that for women with a BMI ≥30 and<35kg/m2 and scheduled for IVF, the weight reduction did not increase their chance of a live birth either in the index cycle or after 2years. It also shows that even in this highly motivated group, a regain of pre-study weight occurred.The 2-year follow-up was financed by grants from the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-70940 and ALFGBG-77690), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Hjalmar Svensson Foundation. Ms Kluge has nothing to disclose. Dr Bergh has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Einarsson has been reimbursed for lectures for Merck and Ferring. Dr Thurin-Kjellberg reports grants from Merck, and reimbursement for lectures from Merck outside the submitted work. Dr Pinborg has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Englund has nothing to disclose.ClinicalTrials.gov number, NCT01566929.
|
|
| 4. |
- Kluge, Linda, 1968
(author)
-
Obesity and IVF outcome. The hope of improvements through weight reduction
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Background: Female obesity is associated with decreased live birth rate (LBR) after in vitro fertilization (IVF) and adverse maternal and perinatal outcomes are increased in obese women compared to normal weight women after spontaneous conceived pregnancies. If the same applies in pregnancies achieved after IVF is scarcely investigated. Publicly funded IVF clinics in Sweden have BMI limits that women must meet to be accepted for IVF. Aim: To assess if weight reduction prior to IVF can increase LBR and cumulative live birth rates (CLBR) in obese women. To explore the women’s views of the having participated in a randomized weight reduction trial prior to IVF and further, to inves-tigate the association between obesity and CLBR and maternal and perinatal outcomes after IVF. Methods: Paper I: A randomized controlled trial (RCT) including 317 infertile obese women, comparing a weight reduction intervention for 16 weeks prior to IVF to immediate IVF, to assess LBR in the two groups. Paper II: A two-year follow-up to assess CLBR and whether the weight reduction achieved in the RCT remained. Paper III: A qualitative interview study, using thematic content analysis, to explore the women’s experiences and views of the RCT. Ten women from the intervention group and seven women from the control group participated in the interviews. Paper IV: A nationwide population-based register study including 126 620 fresh IVF cycles and subsequent frozen embryo transfers (FET) stratified by body mass index (BMI). The fresh cycles were performed between 2007 to 2019 and the main outcome was CLBR. In addition, 58 187 singleton deliveries, achieved after fresh or FET, were included to assess maternal and perinatal outcomes stratified by BMI. The transfers were performed between 2002 to 2020 and the primary outcomes were hypertensive disorders of pregnancy (HDP) and preterm birth less the 37 weeks. Results: Paper I: Despite a substantial weight reduction in the intervention group, mean 9.44 kg no significant difference in LBR could be shown between the weight reduction and IVF group compared to the IVF only group, 29.6% respective 27.5% (differ-ence 2.1%, confidence interval 12.9 to – 8.6). In the weight reduction and IVF group a higher frequency of children born after spontaneous conception was noted. Paper II: The CLBR was similar in the two groups and the women in the weight reduction and IVF group had regained the weight they had lost. Paper 3: The women were happy about the invitation to participate in the RCT. They described the weight reduction treatment as tough, and the support during the weight loss as crucial. They were against a strict BMI limit, and they wished to be evaluated individually. Paper 4: The CLBR decreased in overweight and obese women compared to normal weight women and the adverse maternal and perinatal outcomes increased with severity of obesity. Conclusion: Weight loss prior to IVF did not increase LBRs, nor CLBR after two years. Most interviewed women had a positive attitude to an offer of weight reduction prior to IVF. They wished to be assessed individually and not solely on the basis of their BMI. Overweight and obesity are associated with decreased CLBR and adverse maternal and perinatal outcomes after IVF.
|
|
| 5. |
- Kluge, Linda, 1968, et al.
(author)
-
The association between body mass index and live birth and maternal and perinatal outcomes after in-vitro fertilization: a national cohort study
- 2023
-
In: Frontiers in Endocrinology. - 1664-2392. ; 14
-
Journal article (peer-reviewed)abstract
- Objective: To investigate the association between female body mass index (BMI) and live birth rates and maternal and perinatal outcomes after in-vitro fertilization (IVF). Methods: We performed a national, population-based cohort study including women undergoing IVF between 2002 and 2020. The cohort included 126,620 fresh cycles and subsequent frozen embryo transfers between 2007 and 2019 (subpopulation 1) and 58,187 singleton deliveries between 2002 and 2020 (subpopulation 2). Exposure was female BMI (kg/m2) categorized according to the World Health Organization as underweight (<18.5), normal weight (18.5–24.9, reference), overweight (25.0–29.9), class I obesity (30.0–34.9), class II obesity (35.0–39.9), and class III obesity (≥40.0). The primary outcome in subpopulation 1 was cumulative live birth per started fresh IVF cycle, including fresh and subsequent frozen embryo transfers. Primary outcomes in subpopulation 2 were hypertensive disorders of pregnancy and preterm birth at less than 37 weeks. Risk ratios (RRs) with 95% confidence intervals (CIs) for the association between BMI class and outcomes were calculated using generalized linear models after adjustment for relevant confounders. Results: The cumulative live birth rate decreased significantly with increasing BMI from 32.6% in normal-weight women to 29.4% in overweight women, 27.0% in women in obesity class I, 21.8% in women in obesity class II, and 7.6% in women in obesity class III. The risk of hypertensive disorders of pregnancy increased significantly and progressively with increasing BMI, from 4.6% in normal-weight women to 7.8% in overweight women and 12.5%, 17.9%, and 20.3% in women in obesity classes I, II, and III. The risk of preterm birth followed a similar pattern, from 6.3% in normal-weight women to 7.5% in overweight women and 8.9%, 9.9%, and 15.3% in women in obesity classes I, II, and III. The risks of other perinatal complications, such as perinatal death, showed an even more pronounced increase. Conclusion: Using a large and complete national cohort of women undergoing IVF, we demonstrate a dose-dependent decrease in live birth rate and a substantial increase in maternal and perinatal complications with increasing BMI. Strategies to improve this situation are warranted.
|
|
| 6. |
- Kluge, Linda, 1968, et al.
(author)
-
Women´s experience and long-term perspectives: a qualitative sub-study of a randomized controlled trial on weight reduction prior to in vitro fertilization.
- 2023
-
In: Reproductive, Female and Child Health. ; 2:3, s. 143-151
-
Journal article (peer-reviewed)abstract
- Introduction Obesity is associated with impaired results after in vitro fertilisation (IVF). Consequently, several fertility clinics have set limits of body mass index (BMI) and obese infertile women are thus obliged to lose weight before treatment. Randomised controlled trials (RCTs) have not been able to show an increase in live birth rate after weight reduction before fertility treatment. The purpose of this study was to investigate the patients' experiences and views of participating in a RCT on weight reduction for obese women before IVF, in a long-term perspective. Methods A qualitative follow-up interview study including 17 women was performed between September and December 2020. The interviewed women had all been included in an RCT around 6 years earlier. Semistructured interviews were conducted, the interviews were audio recorded, transcribed verbatim, and analysed using thematic content analysis. Results During the analysis two main themes emerged; ‘Pros and cons related to trial participation’ and ‘Message to health care’. Several women were excited about the prospect of possibly receiving weight reduction before IVF. The women appreciated the support during the intervention but expressed that the diet was tough, and it was hard to maintain the weight loss. Their views regarding BMI limits differed. They advocated an individual assessment regardless of the woman's BMI and expressed that it could be of value to offer weight reduction treatment before IVF. Conclusions Even though the RCT and a 2-year follow-up could not show an increase in live birth rate in the intervention group most women had a positive attitude to weight reduction treatment before IVF. The importance of this study is that the views of the women have been highlighted and their opinions can add valuable information for fertility clinics in their care of obese infertile women.
|
|
| 7. |
- Nilsson, Sofia, et al.
(author)
-
A survey of ovarian reserve and quality of life in female survivors of pediatric cancer.
- 2022
-
In: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 101:1, s. 84-93
-
Journal article (peer-reviewed)abstract
- Childhood cancer is rare; the incidence in Sweden is approximately 16 new cases/100000 children each year. Reduced reproductive function and fertility are well-known side effects of cancer treatment. Anti-Müllerian hormone (AMH) has been shown to correlate well with antral follicle count in healthy women but is currently not recommended as the primary surveillance modality for evaluation of premature ovarian insufficiency in this patient group. Psychological wellbeing related to fertility could affect quality of life and should be included in long-term follow-up. The aim of the study is to present the baseline data from inclusion for a prospective follow-up study of fertility surveillance where both medical and psychological aspects of fertility in female childhood cancer survivors are considered.These are the first results from this longitudinal follow-up cohort study. Female adolescent and young adult survivors of pediatric cancer in Western Sweden were included from January 2016 to December 2018, a total of 54 participants. Median age at inclusion was 21 (15-29) years and median age at cancer diagnosis was 10 (1-17) years. AMH levels, antral follicle count, and data on fertility were recorded at inclusion and will be prospectively followed up. The study includes questionnaires and interviews concerning quality of life. This study is planned to continue until the participants reach the age of 40years.Eighteen of 54 (33%) participants had AMH levels below 1.0µg/L and were considered to have high or very high risk of infertility. Median AMH level was 2.50µg/L. Six women had immediate need of oocyte cryopreservation. Psychological assessment showed that more than one-third of participants (n=20) had elevated anxiety scores.One-third of female survivors of pediatric cancer in the study had high risk of low ovarian reserve, measured by a combination of AMH and antral follicle count, and many had signs of anxiety. The longitudinal study could contribute to better knowledge in the changes of AMH over time for this patient group. Psychological follow-up with questionnaires and interviews evaluating signs of depression and anxiety may serve as a model for future screening programs.
|
|
| 8. |
- Svensson, Henrik, et al.
(author)
-
Inflammatory and metabolic markers in relation to outcome of in vitro fertilization in a cohort of predominantly overweight and obese women.
- 2022
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
-
Journal article (peer-reviewed)abstract
- For overweight and obese women undergoing in vitro fertilization (IVF) the pregnancy and live birth rates are compromised while the underlying mechanisms and predictors are unclear. The aim was to explore the association between adipose tissue-related inflammatory and metabolic markers and the pregnancy and live birth outcome of IVF in a cohort of predominantly overweight and obese women. Serum samples, fulfilling standardizing criteria, were identified from 195 women having participated in either the control (n=131) or intervention (n=64) group of a randomized controlled trial (RCT), seeking to evaluate the effect of a weight reduction intervention on IVF outcome in obese women. Serum high-sensitivity C-reactive protein (hsCRP) and the adipokines leptin and adipocyte fatty acid-binding protein (AFABP) were analyzed for the whole cohort (n=195) in samples collected shortly before IVF [at randomization (control group), after intervention (intervention group)]. Information on age, anthropometry [BMI, waist circumference, waist-to-height ratio (WHtR)], pregnancy and live birth rates after IVF, as well as the spontaneous pregnancy rate, was extracted or calculated from collected data. The women of the original intervention group were also characterized at randomization regarding all variables. Eight women [n=3 original control group (2.3%), n=5 original intervention group (7.8%)] conceived spontaneously before starting IVF. BMI category proportions in the cohort undergoing IVF (n=187) were 1.6/20.1/78.3% (normal weight/overweight/obese). The pregnancy and live birth rates after IVF for the cohort were 35.8% (n=67) and 24.6% (n=46), respectively. Multivariable logistic regression revealed that none of the variables (age, hsCRP, leptin, AFABP, BMI, waist circumference, WHtR) were predictive factors of pregnancy or live birth after IVF. Women of the original intervention group displayed reductions in hsCRP, leptin, and anthropometric variables after intervention while AFABP was unchanged. In this cohort of predominantly overweight and obese women undergoing IVF, neither low-grade inflammation, in terms of hsCRP, other circulating inflammatory and metabolic markers released from adipose tissue (leptin, AFABP), nor anthropometric measures of adiposity or adipose tissue distribution (BMI, waist, WHtR) were identified as predictive factors of pregnancy or live birth rate.Trial registration: ClinicalTrials.gov number, NCT01566929. Trial registration date 30-03-2012, retrospectively registered.
|
|
