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Holte, Jan
Publications (10 of 10) 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
Scherwitzl, E. B., Lundberg, O., Kallner, H. K., Rowland, S. P., Holte, J., Trussell, J., . . . Scherwitzl, R. (2019). Short- and long-term effect of contraceptive methods on fecundity. European journal of contraception & reproductive health care, 24(4), 260-265
Open this publication in new window or tab >>Short- and long-term effect of contraceptive methods on fecundity
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2019 (English)In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 24, no 4, p. 260-265Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of the study was to compare the effect of previously used contraceptive methods on women's short- and long-term fecundity. Use of hormonal contraception (HC) was compared with the use of a contraceptive mobile application (app). Methods: This real-life prospective observational study comprised 2874 women who were attempting to become pregnant using the Natural Cycles mobile app to monitor their fertility. The women registered to use the app between August 2014 and June 2016 with the intention of planning a pregnancy and had previously either used the same app to prevent pregnancy or had recently discontinued HC use. We calculated the average time to pregnancy (TTP) for all women who became pregnant during the study and performed Kaplan-Meier life-table analysis to examine the cumulative probabilities of pregnancy for all women in the study. Results: The average TTP was 2.3 (95% confidence interval [CI] 2.1, 2.4) and 3.7 (95% CI 3.4, 3.9) cycles for women who had previously used Natural Cycles and HC, respectively. The time to reach 30% pregnancy probability for women previously on HC was 1.6 (95% CI 1.5, 1.8) times longer than for women previously using Natural Cycles. There was no significant difference in the 13 cycle cumulated pregnancy probability between the two groups. Conclusion: The results show that fertility awareness-based methods of contraception increase short-term pregnancy rates relative to HC, but have no effect on long-term pregnancy rates.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Conception rate, contraceptive, mobile application, subfertility, time to pregnancy
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-396153 (URN)10.1080/13625187.2019.1621999 (DOI)000472450700001 ()31223036 (PubMedID)
Available from: 2019-11-04 Created: 2019-11-04 Last updated: 2019-11-04Bibliographically approved
Iliadou, A. N., Öberg, A. S., Pege, J., Rodriguez-Wallberg, K. A., Olofsson, J. I., Holte, J., . . . Cesta, C. E. (2019). The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study. BMJ Open, 9, Article ID e028866.
Open this publication in new window or tab >>The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study
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2019 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, article id e028866Article in journal (Refereed) Published
Abstract [en]

Purpose: The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study is a prospectively recruited sample of couples undergoing assisted reproduction in Stockholm and Uppsala county in Sweden. The study was initiated to (1) investigate possible changes in the epigenetic profile of infants inferred through the ART procedures and their consequence and (2) to assess the impact of lifestyle and health exposures on treatment outcome.

Participants: Recruitment took place between September 2011 and December 2013, and in vitro fertilisation (IVF) cycles initiated and pregnancies conceived during this time were followed until December 2014. The cohort includes 971 participants (n= 514 women; n= 457 men), and 129 pregnancies were achieved from the first IVF cycle included in the study.

Findings to date: Self-reported demographic, health and lifestyle data were collected from a baseline questionnaire, and to assess changes to lifestyle, a follow-up questionnaire was issued at the time of oocyte retrieval, and at subsequent IVF cycles. Questionnaire data were linked to data extracted from medical records. Biological samples were collected at baseline: blood for extraction of serum, plasma and DNA, morning and evening saliva samples for cortisol measurement and at delivery including samples of maternal blood, placenta and amniotic fluid, and cord blood for epigenetic analysis.

Future plans: Through the unique identification number assigned to each Swedish citizen at birth or immigration, UppStART study participants will be linked to the Swedish population-based national and quality registers to provide data from prenatal, obstetrical, neonatal and infant care, and subsequent updates will provide data on childhood health and educational outcomes. Collaboration and use of UppStART data is encouraged, and more information about access can be found at www.ki.se/meb/uppstart

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2019
Keywords
assisted reproductive techniques, in vitro fertilisation, infertility, lifestyle, epigenetics
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-402234 (URN)10.1136/bmjopen-2018-028866 (DOI)000502537200210 ()31467051 (PubMedID)
Funder
EU, FP7, Seventh Framework ProgrammeSwedish Research Council, K2011-69X-21871-01-6Swedish Research Council, SIMSAM 340-2013-5867
Available from: 2020-01-16 Created: 2020-01-16 Last updated: 2020-01-16Bibliographically approved
Lindgren, K. E., Yaldir, F. G., Hreinsson, J., Holte, J., Kårehed, K., Sundström Poromaa, I., . . . Åkerud, H. (2018). Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay. Upsala Journal of Medical Sciences, 123(3), 143-152
Open this publication in new window or tab >>Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay
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2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 3, p. 143-152Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim of this study was to assess different patterns of the human embryo secretome analysed as protein levels in culture media. Furthermore, analyses to correlate protein levels with quality and timing to development of human embryos were performed.

Material and methods: Human day-2 cryopreserved embryos were cultured for four days in an EmbryoScope((R)) with a time-lapse camera, and embryo quality was evaluated retrospectively. After culture, the media were collected and relative levels of secreted proteins were analysed using Proseek Multiplex Assays. Protein levels were evaluated in relation to timing to development and the ability to form a blastocyst.

Results: Specific patterns of timing of development of blastocysts were found, where a difference in time to start of cavitation was found between high- and low-quality blastocysts. There appeared to be a correlation between specific protein patterns and successful formation of morulae and blastocysts. Embryos developing into blastocysts had higher levels of EMMPRIN than arrested embryos, and levels of caspase-3 were lower in high- versus low-quality blastocysts. Also, higher levels of VEGF-A, IL-6, and EMMPRIN correlated with shorter times to morula formation.

Conclusions: The secretome and timing to development differ in embryos forming blastocysts and those that become arrested, and in high- versus low-quality blastocysts. The levels of certain proteins also correlate to specific times to development.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Blastocyst, caspase-3, extracellular matrix metalloproteinase inducer, interleukin-6, prediction, secretome, time-lapse, vascular endothelial growth factor A
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-368773 (URN)10.1080/03009734.2018.1490830 (DOI)000446977000002 ()30282508 (PubMedID)
Funder
Swedish Research Council, FF-2017-477Swedish Society of MedicineStiftelsen Olle Engkvist Byggmästare
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Lind, T., Holte, J., Olofsson, J. I., Hadziosmanovic, N., Gudmundsson, J., Nedstrand, E., . . . Rodriguez-Wallberg, K. (2018). Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study. Human Reproduction, 33(2), 238-247
Open this publication in new window or tab >>Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study
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2018 (English)In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 33, no 2, p. 238-247Article in journal (Refereed) Published
Abstract [en]

Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linn, Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linkoping University Hospital (D) and A-rebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P =< 0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = < 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i. e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. WIDER IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
unilateral oophorectomy, live-birth rate, pregnancy, infertility, assisted reproductive technology (ART), IVF, ICSI, ovarian surgery
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-346885 (URN)10.1093/humrep/dex358 (DOI)000424139800008 ()29211889 (PubMedID)
Funder
Swedish Research CouncilSwedish Society of MedicineStockholm County Council
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28Bibliographically 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
Lind, T., Olofsson, J. I., Holte, J., Hadziosmanovic, N., Berglund, L., Gudmundsson, J. & Wallberg, R.-K. W. W. (2015). Reduced clinical pregnancy rates by ART in women with a history of unilateral oophorectomy. Results of a large multi-center cohort study. Paper presented at 31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), JUN 14-17, 2015, Lisbon, PORTUGAL. Human Reproduction, 30(Suppl. 1), 33-33
Open this publication in new window or tab >>Reduced clinical pregnancy rates by ART in women with a history of unilateral oophorectomy. Results of a large multi-center cohort study
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2015 (English)In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 30, no Suppl. 1, p. 33-33Article in journal, Meeting abstract (Other academic) Published
Keywords
unilateral oophorectomy, pregnancy, infertility, assisted reproductive techniques, ovarian surgery
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-264491 (URN)000359740300075 ()
Conference
31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), JUN 14-17, 2015, Lisbon, PORTUGAL
Note

Meeting Abstract: O-075

Available from: 2015-10-19 Created: 2015-10-13 Last updated: 2017-12-01Bibliographically approved
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
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