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Brodin, Thomas
Publications (8 of 8) Show all publications
Vaegter, K. K., Berglund, L., Tilly, J., Hadziosmanovic, N., Brodin, T. & Holte, J. (2019). Construction and validation of a prediction model to minimize twin rates at preserved high live birth rates after IVF. Reproductive Biomedicine Online, 38(1), 22-29
Open this publication in new window or tab >>Construction and validation of a prediction model to minimize twin rates at preserved high live birth rates after IVF
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2019 (English)In: Reproductive Biomedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 38, no 1, p. 22-29Article in journal (Refereed) Published
Abstract [en]

Research question: Elective single-embryo transfer (eSET) at blastocyst stage is widely used to reduce the frequency of multiple pregnancies after IVF. There are, however, concerns about increased risks for the offspring with prolonged embryo culture. Is it possible to select embryos for transfer at the early cleavage stage and still achieve low twin rates at preserved high live birth rates? Design: A prediction model (PM) was developed to optimize eSET based on variables known 2 days after oocyte retrieval (fresh day 2 embryo transfers; double-embryo transfers 1999-2002 (n=2846) and SET 1999-2003 (n=945); n total=3791). Seventy-five variables were analysed for association with pregnancy chance and twin risk and combined for PM construction. This PM was validated in 2004-2016 including frozen-thawed transfers (FET), to compare cumulative live birth rate (CLBR) and twin rate before (1999-2002 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2007, n=3495) and after (2004-2011 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2016, n=11195) implementing the model. Results: The PM was constructed from four independent variables: female age, embryo score, ovarian sensitivity and treatment history. The calibration, i.e. the fit of observed versus predicted results, was excellent both at construction and at validation. Without compromising CLBR, twin rate was reduced from 25.2% to 3.8%, accompanied by profound improvements in perinatal outcome. Conclusion: The results provide the first successful construction, validation and impact analysis of a day 2 transfer PM to reduce multiple pregnancies.

Keywords
Double-embryo transfer (DET), IVF/ICSI outcome, Multiple pregnancy, Prediction model, Single-embryo transfer (SET)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-375845 (URN)10.1016/j.rbmo.2018.09.020 (DOI)000455992700004 ()30518500 (PubMedID)
Available from: 2019-02-01 Created: 2019-02-01 Last updated: 2019-02-01Bibliographically approved
Vaegter, K. K., Ghukasyan Lakic, T., Olovsson, M., Berglund, L., Brodin, T. & Holte, J. (2017). Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments?: Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers. Fertility and Sterility, 107(3), 641-+
Open this publication in new window or tab >>Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments?: Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers
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2017 (English)In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 107, no 3, p. 641-+Article in journal (Refereed) Published
Abstract [en]

Objective: To construct a prediction model for live birth after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and single-embryo transfer (SET) after 2 days of embryo culture. Design: Prospective observational cohort study. Setting: University-affiliated private infertility center. Patient(s): SET in 8,451 IVF/ICSI treatments in 5,699 unselected consecutive couples during 1999-2014. Intervention(s): A total of 100 basal patient characteristics and treatment data were analyzed for associations with live birth after IVF/ICSI (adjusted for repeated treatments) and subsequently combined for prediction model construction. Main Outcome Measure(s): Live birth rate (LBR) and performance of live birth prediction model. Result(s): Embryo score, treatment history, ovarian sensitivity index (OSI; number of oocytes/total dose of FSH administered), female age, infertility cause, endometrial thickness, and female height were all independent predictors of live birth. A prediction model (training data set; n = 5,722) based on these variables showed moderate discrimination, but predicted LBR with high accuracy in subgroups of patients, with LBR estimates ranging from <10% to >40%. Outcomes were similar in an internal validation data set (n = 2,460). Conclusion(s): Based on 100 variables prospectively recorded during a 15-year period, a model for live birth prediction after strict SET was constructed and showed excellent calibration in internal validation. For the first time, female height qualified as a predictor of live birth after IVF/ICSI.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2017
Keywords
IVF, prediction model, live birth rate, multiple pregnancy, single-embryo transfer
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-320270 (URN)10.1016/j.fertnstert.2016.12.005 (DOI)000397985500022 ()28108009 (PubMedID)
Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2017-04-18Bibliographically approved
Brodin, T., Hadziosmanovic, N., Berglund, L., Olovsson, M. & Holte, J. (2015). Comparing four ovarian reserve markers: associations with ovarian response and live births after assisted reproduction. Acta Obstetricia et Gynecologica Scandinavica, 94(10), 1056-1063
Open this publication in new window or tab >>Comparing four ovarian reserve markers: associations with ovarian response and live births after assisted reproduction
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2015 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 94, no 10, p. 1056-1063Article in journal (Refereed) Published
Abstract [en]

Introduction. We compared the ability of four different ovarian reserve tests (ORTs) to predict live births per started in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycle, and poor and excessive response to controlled ovarian hyperstimulation. Material and methods. This was a cohort study in a private infertility center in collaboration with Uppsala University, comprising 1230 IVF-ICSI cycles in 892 consecutive women between April 2008 and June 2011. Anti-Mullerian hormone (AMH) levels, antral follicle counts (AFC), combinations of basal levels of follicle-stimulating hormone and luteinizing hormone, and menstrual cycle lengths were analyzed for correlation and treatment outcome prediction in age-adjusted statistical models. Stepwise multivariable generalized estimating equation analyses were carried out in a sub-group with complete data on all four ORTs (620 cycles in 443 women). Odds ratios and c-statistics were calculated in the largest available set of data for each significant variable. Primary outcomes were live birth rate per started cycle and poor and excessive ovarian response to controlled ovarian hyperstimulation (defined by the ovarian sensitivity index). Results. All ORTs correlated significantly with each other, with the strongest correlation between AFC and AMH (r = 0.71, p < 0.0001). Univariately, AMH and age equivalently predicted live birth (c-statistic 0.61), and together they provided a significantly better model (c-statistic 0.64). For prediction of poor and excessive response the best model included AMH, AFC and age (c-statistic 0.89). Conclusions. AMH improves the ability to estimate live birth rates after assisted reproduction compared with female age alone. AMH, AFC and age together constituted the best model for prediction of ovarian response.

Keywords
Antral follicle counts, anti-Mullerian hormone, follicle-stimulating hormone, in vitro fertilization, menstrual cycle length, ovarian reserve tests
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-265824 (URN)10.1111/aogs.12710 (DOI)000362511300005 ()26184379 (PubMedID)
Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2017-12-01
Rhenman, A., Berglund, L., Brodin, T., Olovsson, M., Milton, K., Hadziosmanovic, N. & Holte, J. (2015). Which set of embryo variables is most predictive for live birth?: A prospective study in 6252 single embryo transfers to construct an embryo score for the ranking and selection of embryos. Human Reproduction, 30(1), 28-36
Open this publication in new window or tab >>Which set of embryo variables is most predictive for live birth?: A prospective study in 6252 single embryo transfers to construct an embryo score for the ranking and selection of embryos
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2015 (English)In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 30, no 1, p. 28-36Article in journal (Refereed) Published
Abstract [en]

STUDY QUESTION: Which embryo score variables are most powerful for predicting live birth after single embryo transfer (SET) at the early cleavage stage? SUMMARY ANSWER: This large prospective study of visual embryo scoring variables shows that blastomere number (BL), the proportion of mononucleated blastomeres (NU) and the degree of fragmentation (FR) have independent prognostic power to predict live birth. WHAT IS KNOWN ALREADY: Other studies suggest prognostic power, at least univariately and for implantation potential, for all five variables. A previous study from the same centre on double embryo transfers with implantation as the end-point resulted in the integrated morphology cleavage (IMC) score, which incorporates BL, NU and EQ. STUDY DESIGN, SIZE AND DURATION: A prospective cohort study of IVF/ICSI SET on Day 2 (n = 6252) during a 6-year period (2006-2012). The five variables (BL NU, FR, EQ and symmetry of cleavage (SY)) were scored in 3- to 5-step scales and subsequently related to clinical pregnancy and LBR. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 4304 women undergoing IVF/ICSI in a university-affiliated private fertility clinic were included. Generalized estimating equation models evaluated live birth (yes/no) as primary outcome using the embryo variables as predictors. Odds ratios with 95% confidence intervals and P-values were presented for each predictor. The C statistic (i.e. area under receiver operating characteristic curve) was calculated for each model. Model calibration was assessed with the Hosmer-Lemeshow test. A shrinkage method was applied to remove bias in c statistics due to over-fitting. MAIN RESULTS AND THE ROLE OF CHANCE: LBR was 27.1% (1693/6252). BL, NU, FR and EQ were univariately highly significantly associated with LBR. In a multivariate model, BL, NU and FR were independently significant, with c statistic 0.579 (age-adjusted c statistic 0.637). EQ did not retain significance in the multivariate model. Prediction model calibration was good for both pregnancy and live birth. We present a ranking tree with combinations of values of the BL, NU and FR embryo variables for optimal selection of the embryo/s to transfer, providing a revised IMC score. The five embryo variables had similar effects over all age groups. LIMITATIONS, REASONS FOR CAUTION: Limitations of the present study are those inherent for real-time visual scoring, including risks of inter-observer variation and the hazards of fixed time-point scoring procedures in a dynamic process. The study is restricted to Day-2 transfers. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge this is the largest prospective, SET study performed with the explicit aim of constructing an evidence-based embryo score for the ranking and selection of early cleavage stage embryos. In line with previous research, our data suggest that the symmetry of cleavage variable may be omitted when scoring embryos in the early cleavage stage. We suggest that, following validation in other populations, the revised IMC score may be used when international standards for embryo scoring are discussed.

Keywords
embryo morphology, embryo score, implantation potential, prediction, embryo transfer
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-249035 (URN)10.1093/humrep/deu295 (DOI)000350146100006 ()25376459 (PubMedID)
Available from: 2015-04-23 Created: 2015-04-10 Last updated: 2017-12-04Bibliographically approved
Brodin, T., Hadziosmanovic, N., Berglund, L., Olovsson, M. & Holte, J. (2013). Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction. Journal of Clinical Endocrinology and Metabolism, 98(3), 1107-1114
Open this publication in new window or tab >>Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction
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2013 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 3, p. 1107-1114Article in journal (Refereed) Published
Abstract [en]

Context: Previous studies have suggested that antimullerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. Objective: The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. Design: The study was a prospective cohort study between April 2008 and June 2011. Setting: The study was done at a university-affiliated private infertility center. Patients: The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. Intervention(s): AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. Main Outcome Measures: Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured. Results: AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH < 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH > 2.94 ng/mL (75th percentile), P-trend < .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. Conclusions: AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.

Keywords
Anti-Mullerian Hormone, Polycystic-Ovary-Syndrome, Antral Follicle Counts, Menstrual-Cycle, Women, Ivf; Reserve, Age, Stimulatio, Embryo
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-192987 (URN)10.1210/jc.2012-3676 (DOI)000316417200060 ()23408576 (PubMedID)
Available from: 2013-01-28 Created: 2013-01-28 Last updated: 2017-12-06Bibliographically approved
Brodin, T. (2013). Ovarian Reserve and Assisted Reproduction. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Ovarian Reserve and Assisted Reproduction
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Treatment success in IVF-ICSI is mainly limited by female age, but differences in ovarian reserve (OR; the remaining pool of oocytes and their quality) between individuals modify treatment prerequisites among women of similar age. OR may be assessed by OR tests (ORTs). The main aims of this work were to study menstrual cycle length (MCL), basal levels of circulating gonadotrophins, antral follicle count (AFC) and serum Anti-Müllerian hormone (AMH) levels and their associations with and prognostic capacities regarding IVF-ICSI outcome in large cohorts of unselected women.

Age-adjusted MCL was positively and linearly associated with pregnancy rates (PRs), live-birth rates (LBRs) and ovarian response to controlled ovarian hyperstimulation. An MCL of >34 days almost doubled the LBR compared with an MCL of <26 days.

The grouped variable ‘combined FSH and LH levels’ was superior to both individual gonadotrophin levels and the LH:FSH ratio. The highest mean PR was seen in connection with a combination of FSH <6.7 U/l with LH >4.9 U/l; PRs were lowest when FSH-LH levels were opposite to this (high-low) and intermediate when FSH-LH levels were low-low or high-high. Associations with LBR and ovarian response were similar as those for PR.

AFCs and serum AMH levels were positively and log-linearly associated with PR, LBR and ovarian response. Success rates levelled out above AFC 30 or AMH 5 ng/ml. Treatment outcome was superior among women with polycystic ovaries.

Among the studied ORTs, logAFC and logAMH concentration correlated most strongly. After multivariate testing, entering all studied ORTs, AMH and female age remained independently associated with LBR. AMH + AFC + age predicted both poor and excessive ovarian responses with high accuracy.

Adjusting for age and oocyte yield, all ORTs remained significant for LBR, implying that ORTs also capture information on oocyte quality.

In conclusion, measures of OR are strongly associated with PR, LBR and ovarian response in a log-linear fashion, and partly reflect oocyte quality. The OR spectrum is continuous, from small ‘oligofollicular’ ovaries (the low extreme) to polycystic ovaries (the high extreme). Among the studied ORTs, AMH together with age provide the most powerful basal estimate for IVF/ICSI outcome.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. p. 88
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 865
Keywords
AFC, AMH, anti-Müllerian hormone, antral follicle count, follicle-stimulating hormone, FSH, ICSI, infertility, intracytoplasmic sperm injection, in vitro fertilization, IVF, LH, live birth, luteinizing hormone, menstrual cycle, menstrual cycle length, ovarian reserve, pregnancy, reproductive endocrinology, reproductive technology
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-192998 (URN)978-91-554-8592-4 (ISBN)
Public defence
2013-03-22, Sal IX, Universitetshuset, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2013-02-28 Created: 2013-01-28 Last updated: 2013-03-05Bibliographically approved
Brodin, T., Berglund, L., Hadziosmanovic, N., Bergh, T., Olovsson, M. & Holte, J. (2012). Antimullerian hormone predicts pregnancy and live-birth rates after assisted reproduction and reflect oocyte quality besides oocyte quantity. Acta Obstetricia et Gynecologica Scandinavica, 91, 35-35
Open this publication in new window or tab >>Antimullerian hormone predicts pregnancy and live-birth rates after assisted reproduction and reflect oocyte quality besides oocyte quantity
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2012 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, p. 35-35Article in journal, Meeting abstract (Other academic) Published
Keywords
AMH, IVF, ICSI, pregnancy, live birth, oocyte quality
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-177430 (URN)000304987600047 ()
Available from: 2012-12-13 Created: 2012-07-13 Last updated: 2017-12-06Bibliographically approved
Holte, J., Brodin, T., Berglund, L., Hadziosmanovic, N., Olovsson, M. & Bergh, T. (2011). Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries. Fertility and Sterility, 96(3), 594-599
Open this publication in new window or tab >>Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries
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2011 (English)In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, no 3, p. 594-599Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. Design: Prospective observational study. Setting: University-affiliated private infertility center. Patient(s): 2,092 women undergoing 4,308 IVF-ICSI cycles. Intervention(s): AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. Main Outcome Measure(s): Pregnancy rate, live-birth rate, and stimulation outcome parameters. Result(s): The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC similar to 30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. Conclusion(s): Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity.

Keywords
AFC, antral follicle count, infertility, IVF, ovarian reserve, PCO
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-158865 (URN)10.1016/j.fertnstert.2011.06.071 (DOI)000294417000026 ()
Available from: 2011-09-20 Created: 2011-09-19 Last updated: 2017-12-08Bibliographically approved
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