Abstract
STUDY QUESTION
What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in ...a three-country network?
SUMMARY ANSWER
In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively.
WHAT IS KNOWN ALREADY
Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter ‘tissue activity’.
STUDY DESIGN, SIZE, DURATION
Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved.
MAIN RESULTS AND THE ROLE OF CHANCE
The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11).
LIMITATIONS, REASONS FOR CAUTION
The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated.
WIDER IMPLICATIONS OF THE FINDINGS
This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required.
STUDY FUNDING/COMPETING INTEREST
This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests.
TRIAL REGISTRATION NUMBER
None.
Data re-sampling methods such as delete-one jackknife, bootstrap or the sub-sample covariance are common tools for estimating the covariance of large-scale structure probes. We investigate different ...implementations of these methods in the context of cosmic shear two-point statistics. Using lognormal simulations of the convergence field and the corresponding shear field we generate mock catalogues of a known and realistic covariance. For a survey of
${\sim } 5000 \deg ^2$
we find that jackknife, if implemented by deleting sub-volumes of galaxies, provides the most reliable covariance estimates. Bootstrap, in the common implementation of drawing sub-volumes of galaxies, strongly overestimates the statistical uncertainties. In a forecast for the complete 5-yr Dark Energy Survey, we show that internally estimated covariance matrices can provide a large fraction of the true uncertainties on cosmological parameters in a 2D cosmic shear analysis. The volume inside contours of constant likelihood in the Ωm–σ8 plane as measured with internally estimated covariance matrices is on average ≳85 per cent of the volume derived from the true covariance matrix. The uncertainty on the parameter combination
$\Sigma _8 \sim \sigma _8 \Omega _{\rm m}^{0.5}$
derived from internally estimated covariances is ∼90 per cent of the true uncertainty.
This work aims to study the distribution of the luminous and dark matter in Coma early-type galaxies. Dynamical masses obtained under the assumption that mass follows light do not match with the ...masses of strong gravitational lens systems of similar velocity dispersions. Instead, dynamical fits with dark matter haloes are in good agreement with lensing results. We derive mass-to-light ratios of the stellar populations from Lick absorption line indices, reproducing well the observed galaxy colours. Even in dynamical models with dark matter haloes the amount of mass that follows the light increases more rapidly with the galaxy velocity dispersion than expected for a constant stellar initial mass function (IMF). While galaxies around σeff≈ 200 km s−1 are consistent with a Kroupa IMF, the same IMF underpredicts luminous dynamical masses of galaxies with σeff≈ 300 km s−1 by a factor of 2 and more. A systematic variation in the stellar IMF with the galaxy velocity dispersion could explain this trend with a Salpeter IMF for the most massive galaxies. If the IMF is instead constant, then some of the dark matter in high-velocity-dispersion galaxies must follow a spatial distribution very similar to that of the light. A combination of both, a varying IMF and a component of dark matter that follows the light is possible as well. For a subsample of galaxies with old stellar populations, we show that the tilt in the Fundamental Plane can be explained by systematic variations of the total (stellar + dark) mass inside the effective radius. We tested commonly used mass estimator formulae, finding them accurate at the 20-30 per cent level.
We present the weak lensing analysis of the Wide-Field Imager Sunyaev–Zel'dovich Cluster of Galaxy (WISCy) sample, a set of 12 clusters of galaxies selected for their Sunyaev–Zel'dovich (SZ) effect. ...After developing new and improved methods for background selection and determination of geometric lensing scaling factors from absolute multiband photometry in cluster fields, we compare the weak lensing mass estimate with public X-ray and SZ data. We find consistency with hydrostatic X-ray masses with no significant bias, no mass dependent bias and less than 20 per cent intrinsic scatter and constrain
$f_{\rm{gas},500c}=0.128^{+0.029}_{-0.023}$
. We independently calibrate the South Pole Telescope significance–mass relation and find consistency with previous results. The comparison of weak lensing mass and Planck Compton parameters, whether extracted self-consistently with a mass–observable relation (MOR) or using X-ray prior information on cluster size, shows significant discrepancies. The deviations from the MOR strongly correlate with cluster mass and redshift. This could be explained either by a significantly shallower than expected slope of Compton decrement versus mass and a corresponding problem in the previous X-ray based mass calibration, or a size or redshift dependent bias in SZ signal extraction.
Intrinsic variations of the projected density profiles of clusters of galaxies at fixed mass are a source of uncertainty for cluster weak lensing. We present a semi-analytical model to account for ...this effect, based on a combination of variations in halo concentration, ellipticity and orientation, and the presence of correlated haloes. We calibrate the parameters of our model at the 10 per cent level to match the empirical cosmic variance of cluster profiles at
$M_{200m}\approx 10^{14}\ldots 10^{15}\,h^{-1}{\,\mathrm{M}_{\odot }}$
, z = 0.25…0.5 in a cosmological simulation. We show that weak lensing measurements of clusters significantly underestimate mass uncertainties if intrinsic profile variations are ignored, and that our model can be used to provide correct mass likelihoods. Effects on the achievable accuracy of weak lensing cluster mass measurements are particularly strong for the most massive clusters and deep observations (with ≈20 per cent uncertainty from cosmic variance alone at
$M_{200m}\approx 10^{15}\,h^{-1}{\,\mathrm{M}_{\odot }}$
and z = 0.25), but significant also under typical ground-based conditions. We show that neglecting intrinsic profile variations leads to biases in the mass-observable relation constrained with weak lensing, both for intrinsic scatter and overall scale (the latter at the 15 per cent level). These biases are in excess of the statistical errors of upcoming surveys and can be avoided if the cosmic variance of cluster profiles is accounted for.
We present the completed KMOS3D survey, an integral field spectroscopic survey of 739 \(\mathrm{log}({M}_{\star }/{M}_{\odot })\gt 9\) galaxies at 0.6 < z < 2.7 using the K-band Multi Object ...Spectrograph (KMOS) at the Very Large Telescope. The KMOS3D survey provides a population-wide census of kinematics, star formation, outflows, and nebular gas conditions both on and off the star-forming galaxy main sequence through the spatially resolved and integrated properties of Hα, N ii, and S ii emission lines. We detect Hα emission for 91% of galaxies on the main sequence of star formation and 79% overall. The depth of the survey has allowed us to detect galaxies with star formation rates below 1 M ⊙ yr−1, as well as to resolve 81% of detected galaxies with ≥3 resolution elements along the kinematic major axis. The detection fraction of Hα is a strong function of both color and offset from the main sequence, with the detected and nondetected samples exhibiting different spectral energy distribution shapes. Comparison of Hα and UV+IR star formation rates reveal that dust attenuation corrections may be underestimated by 0.5 dex at the highest masses (\(\mathrm{log}({M}_{\star }/{M}_{\odot })\gt 10.5\)). We confirm our first year results of a high rotation-dominated fraction (monotonic velocity gradient and v rot/\({\sigma }_{0}\gt \sqrt{3.36}\)) of 77% for the full KMOS3D sample. The rotation-dominated fraction is a function of both stellar mass and redshift, with the strongest evolution measured over the redshift range of the survey for galaxies with \(\mathrm{log}({M}_{\star }/{M}_{\odot })\lt 10.5\). With this paper, we include a final data release of all 739 observed objects (http://www.mpe.mpg.de/ir/KMOS3D).
The original algorithm that classified triple-negative breast cancer (TNBC) into six subtypes has recently been revised. The revised algorithm (TNBCtype-IM) classifies TNBC into five subtypes and a ...modifier based on immunological (IM) signatures. The molecular signature may differ between cancer cells in vitro and their respective tumor xenografts. We identified cell lines with concordant molecular subtypes regardless of classification algorithm or analysis of cells in vitro or in vivo, to establish a panel of clinically relevant molecularly stable TNBC models for translational research. Gene expression data were used to classify TNBC cell lines using the original and the revised algorithms. Tumor xenografts were established from 17 cell lines and subjected to gene expression profiling with the original 2188-gene algorithm TNBCtype and the revised 101-gene algorithm TNBCtype-IM. A total of six cell lines (SUM149PT (BL2), HCC1806 (BL2), SUM149PT (BL2), BT549 (M), MDA-MB-453 (LAR), and HCC2157 (BL1)) maintained their subtype classification between in vitro and tumor xenograft analyses across both algorithms. For TNBC molecular classification-guided translational research, we recommend using these TNBC cell lines with stable molecular subtypes.
We present results for a galaxy-galaxy lensing study based on imaging data from the Canada-France-Hawaii Telescope Legacy Survey Wide. From a 12 million object multicolour catalogue for 124 deg2 of ...photometric data in the u*g
′
r
′
i
′
z
′ filters, we compute photometric redshifts (with a scatter of σΔz/(1 + z) = 0.033 and an outlier rate of η = 2.0 per cent for i
′ ≤ 22.5) and extract galaxy shapes down to i
′ = 24.0. We select a sample of lenses and sources with 0.05 < z
d ≤ 1 and 0.05 < z
s ≤ 2. We fit three different galaxy halo profiles to the lensing signal, a singular isothermal sphere (SIS), a truncated isothermal sphere (BBS) and a universal density profile (NFW). We derive velocity dispersions by fitting an SIS out to 100 h
−1 kpc to the excess surface mass density ΔΣ and perform maximum likelihood analyses out to a maximum scale of 2 h
−1 Mpc to obtain halo parameters and scaling relations. We find luminosity scaling relations of σred ∝ L
0.24 ± 0.03 for the red lens sample, σblue ∝ L
0.23 ± 0.03 for blue lenses and σ ∝ L
0.29 ± 0.02 for the combined lens sample with zero-points of
,
and σ* = 135 ± 2 km s−1 at a chosen reference luminosity
. The steeper slope for the combined sample is due to the different zero-points of the blue and red lenses and the fact that blue lenses dominate at low luminosities and red lenses at high luminosities. The mean effective redshifts for the lens samples are 〈z
red〉 = 0.28 for red lenses, 〈z
blue〉 = 0.35 for blue lenses and 〈z〉 = 0.34 for the combined lens sample. The BBS maximum likelihood analysis yields for the combined sample a velocity dispersion of
km s− 1 and a truncation radius of
kpc, corresponding to a total mass of
and a mass-to-light (M/L) ratio of
at
. At a given luminosity, both velocity dispersion σ and truncation radius s are larger for red galaxies than for blue galaxies. For an NFW profile, we measure at
a virial radius of
kpc and a concentration parameter of
, implying a virial mass of
. At L* for blue galaxies the concentration parameter is slightly higher than for red galaxies and r
200 is significantly lower. For the combined sample, if described as a single power law, the M/L ratio scales as
, the concentration parameter scales as
. Analysing the M/L scaling for red and blue galaxies separately, we find that a broken power law (with a flat slope at high luminosities) provides a more appropriate description for red and possibly also for blue galaxies. We measure M
200/M
star for red galaxies over 2.5 decades in stellar mass. We find a minimum for this ratio at M
star ∼ 3-4 × 1010 h
− 2 M with a strong increase for lower stellar masses.
Purpose
BRCA
mutation carriers have an increased risk of developing breast or ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is associated with a decrease in risk for tubal and ...ovarian cancer. Hormone replacement therapy (HRT) may increase breast, ovarian, and endometrial cancer risk in the general population. This review analyses the published data on HRT and risk of cancer in
BRCA
mutation carriers with and without RRBSO.
Methods
We included all relevant articles published in English from 1995 to October 2020. Sources were identified through a search on PubMed and Cochrane Library.
Results
We included one case–control and one retrospective cohort study on ovarian and one case–control study on endometrial cancer risk and HRT in
BRCA
mutation carriers. Regarding breast cancer risk, one case–control study on
BRCA
mutation carriers with and without RRBSO and one case–control study, one Markov chain decision model, two prospective cohort studies, and one metaanalysis on carriers after RRBSO were included. For ovarian cancer, results were ambiguous. For breast cancer, most studies did not find an adverse effect associated with HRT. However, some of the studies found a risk modification associated with different formulations and duration of use.
Conclusion
Although data are limited, HRT does not seem to have a relevant effect on cancer risk in
BRCA
mutation carriers. RRBSO should not be postponed to avoid subsequent HRT in this population. Adequate HRT after RRBSO should be offered to avoid chronic diseases resulting from low estrogen levels. However, further data on the safety of different formulations are needed.
Purpose
BRCA
mutation carriers have an increased risk of developing breast or ovarian cancer. Oral contraception (OC) is known to increase breast cancer and reduce ovarian cancer risk in the general ...population. This review analyses the published data on OC and risk of cancer in
BRCA
mutation carriers.
Methods
We included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library.
Results
We included four meta-analyses, one review, one case–control study and one retrospective cohort study on the association between ovarian cancer and OC in
BRCA
mutation carriers. All report a risk reduction for the OC users and several also describe an inverse correlation with duration of use. Regarding breast cancer, we included four meta-analyses, one review, one case–control study, two case-only studies, one prospective and one retrospective cohort study. Some studies report a risk elevation, while others did not find an association between OC use and breast cancer in
BRCA
mutation carriers. In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of OC.
Conclusion
Oral contraception leads to a risk reduction of ovarian cancer also in
BRCA
mutation carriers. An increase in breast cancer risk due to OC cannot be excluded. Women with BRCA mutation who consider OC use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods. OC should not be used for the prevention of ovarian cancer in this population.
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