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Category Archives: Human Reproduction
Disclosure behaviour and intentions among 111 couples following treatment with oocytes or sperm from identity-release donors: follow-up at offspring age 1-4 years
STUDY QUESTION
Do heterosexual parents of young children following oocyte donation (OD) and sperm donation (SD) tell or intend to tell their offspring about the way he/she was conceived?
SUMMARY ANSWER
Following successful treatment with oocytes or sperm from identity-release donors in Sweden, almost all heterosexual couples intend to tell their offspring about the way he/she was conceived and some start the information-sharing process very early.
WHAT IS KNOWN AND WHAT THIS PAPER ADDS
Although the Swedish legislation on identity-release gamete donors has been in effect since 1985, there is a discrepancy between the behaviour of donor-insemination parents and the legal intention that offspring be informed about their genetic origin. The present study contributes data on a relatively large sample of oocyte and sperm recipient couples' intended compliance with the Swedish legislation.
DESIGN AND DATA COLLECTION METHOD
The present study constitutes a follow-up assessment of heterosexual couples who had given birth to a child following treatment with donated oocytes. Data collection was performed during 2007–2011; participants individually completed a questionnaire when the child was between 1 and 4 years of age.
PARTICIPANTS AND SETTING
The present study is part of the Swedish Study on Gamete Donation, a prospective longitudinal cohort study including all fertility clinics performing gamete donation in Sweden. For children conceived via OD, 107 individuals (including 52 couples and 3 individuals) agreed to participate (73% response). For children conceived via SD, the response rate was 70% (n = 122 individuals, including 59 couples and 4 individuals). Mean age of participants was 34 years (SD 4.4) and they reported a high level of education.
MAIN RESULTS
The majority of participants (78%) planned to tell the child about the donation, 16% had already started the information-sharing process and 6% planned not to tell their child about the donation or were undecided. Many were unsure about a suitable time to start the disclosure process and desired more information about strategies and tools for information sharing. Agreement on disclosure to offspring within the couple was related to the quality of the partner relationship.
BIAS AND GENERALIZABILITY
There is a risk of selection bias, with gamete recipients preferring secrecy and non-disclosure declining study participation. The results may be regarded as partly generalizable to heterosexual couples with young children following treatment with gametes from legislatively mandated identity-release donors in an established donor programme.
STUDY FUNDING/COMPETING INTERESTS
Study funding by Merck Serono, The Swedish Research Council and The Family Planning Fund in Uppsala. No conflicts of interest to declare.
Posted in Human Reproduction
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Uterine leiomyomata and fecundability in the Right from the Start study
BACKGROUND
Previous research suggests the removal of uterine leiomyomata may improve ability to conceive. Most of this previous research was conducted in infertility clinics. We investigated the association between leiomyoma characteristics on time to pregnancy among women enrolled from the general population.
METHODS
We enrolled a cohort study of women in early pregnancy. Participants retrospectively reported their time to conception. Leiomyomata characteristics were determined by first-trimester ultrasound. We used discrete time hazard models to estimate the effects of uterine leiomyomata on time to pregnancy.
RESULTS
In this population of 3000 women, 11% (324) with one or more leiomyomata, we found no association between leiomyomata presence, type, location, segment or size on time to pregnancy.
CONCLUSIONS
These results suggest that leiomyomata have little effect on time to pregnancy in this cohort of women. The study excluded women who had been treated for infertility, and this may have resulted in underestimation of the association. However, differences between our study and previous studies in specialty clinics may be, in part, attributable to differences between our community-recruited population of women and women receiving fertility care, as well as difference in leiomyomata size or type in women having myomectomies to treat infertility.
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Integration of patient characteristics and the results of Chlamydia antibody testing and hysterosalpingography in the diagnosis of tubal pathology: an individual patient data meta-analysis
BACKGROUND
Tubal patency tests are routinely performed in the diagnostic work-up of subfertile patients, but it is unknown whether these diagnostic tests add value beyond the information obtained by medical history taking and findings at physical examination. We used individual patient data meta-analysis to assess this question.
METHODS
We approached authors of primary studies for data sets containing information on patient characteristics and results from tubal patency tests, such as Chlamydia antibody test (CAT), hysterosalpingography (HSG) and laparoscopy. We used logistic regression to create models that predict tubal pathology from medical history and physical examination alone, as well as models in which the results of tubal patency tests are integrated in the patient characteristics model. Laparoscopy was considered to be the reference test.
RESULTS
We obtained data from four studies reporting on 4883 women. The duration of subfertility, number of previous pregnancies and a history of previous pelvic inflammatory disease (PID), pelvic surgery or Chlamydia infection qualified for the patient characteristics model. This model showed an area under the receiver operating characteristic curve (AUC) of 0.63 [95% confidence interval (CI) 0.61–0.65]. For any tubal pathology, the addition of HSG significantly improved the predictive performance to an AUC of 0.74 (95% CI 0.73–0.76) (P < 0.001). For bilateral tubal pathology, the addition of both CAT and HSG increased the predictive performance to an AUC of 0.76 (95% CI 0.74–0.79).
CONCLUSIONS
In the work-up for subfertile couples, the combination of patient characteristics with CAT and HSG results gives the best diagnostic performance for the diagnosis of bilateral tubal pathology.
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Simple adaptations to the Templeton model for IVF outcome prediction make it current and clinically useful
STUDY QUESTION
What is the validity of the Templeton model (TM) in predicting live birth (LB) for a couple starting an IVF/ICSI cycle?
SUMMARY ANSWER
A centre-specific model based on the original predictors of the TM may reach a sufficient level of accuracy to be used in every day practice, with a few simple adaptations.
WHAT IS KNOWN AND WHAT THIS PAPER ADDS
The TM seems the best predictive model of LB in IVF. However, previous validations of the TM suggest a lack of discrimination and calibration which means that it is not used in regular practice. We confirm this finding, and argue that such results are predictable, and essentially due to a strong centre effect. We provide evidence that the TM constitutes a useful reference reflecting a high proportion of the patient-mix effect since the parameters of the model remain invariant among centres, but also across various cultures, countries and types of hospitals. The only difference was the intercept value, interpreted as the measurement of the global performance of one centre, in particular, for a population of reference.
STUDY DESIGN
The validity of the TM was tested by a retrospective analysis all IVF/ICSI cycles (n = 12 901) in our centre since 2000.
PARTICIPANTS, SETTING AND METHODS
All IVF/ICSI cycles were included in the analysis. The model discrimination was evaluated by C-statistics, calculated as the area under the curve of an ROC curve. The TM was then adjusted for our data and additional variables were assessed.
MAIN RESULTS AND THE ROLE OF CHANCE
Poor calibration and discrimination (C = 0.64) was observed in conformity with previous external validations. Fitting the TM to our centre constituted the first substantial improvement in prediction accuracy of discrimination (C = 0.69) and calibration. We identified an important linear time trend effect and the added value of three other predictors (FSH, smoking habits and BMI) that significantly improved the model (C = 0.71).
BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION
Bias due to missing data handling was assessed through sensitivity analyses.
GENERALIZABILITY TO OTHER POPULATIONS
Neither the TM nor any other models based on some centres are directly applicable to other centres. However, the TM constitutes a useful basis to build an accurate centre-specific model.
STUDY FUNDING/COMPETING INTEREST(S)
There were no commercial relationships (i.e. consultancies, patent-licensing agreements) that might pose a conflict of interest in connection with the submitted manuscript. The objective of this research was not directed toward any treatment effects.
Posted in Human Reproduction
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Factors associated with dizygotic twinning after IVF treatment with double embryo transfer
BACKGROUND
Dizygotic twin pregnancies after IVF treatment are the result of multiple embryos transferred into the uterine cavity, followed by successful double implantation. Factors that increase the chance of multiple implantation after IVF are relatively unknown. The present study aimed to investigate whether features of body composition, such as maternal height, weight and body mass index (BMI) are associated with an increased chance of dizygotic twinning after IVF with double embryo transfer (DET).
METHODS
This study was conducted using data from a large Dutch nationwide cohort that comprised 19 861 women who had IVF or ICSI treatment between 1983 and 1995 (OMEGA study). First ‘fresh’ IVF and ICSI cycles with DET resulting in a delivery of a singleton or twin (living as well as stillborn) were selected. A multivariable logistic regression analysis was performed, with the delivery of a singleton or twin as the dependent variable and height, weight, BMI, maternal age, number of retrieved oocytes, use of alcohol, smoking, highest level of education and parity as independent variables.
RESULTS
Of the 6598 women who completed their first IVF or ICSI cycle, 2375 had DET, resulting in 496 deliveries of 371 singletons and 125 twins. Multivariable regression analysis revealed that tall women (>1.74 cm) and women with a high number of retrieved oocytes (>8) had an increased chance of dizygotic twinning [OR: 1.8 (95% CI: 1.0–3.4) and OR: 2.2 (95% CI: 1.3–3.8), respectively].
CONCLUSIONS
Our data demonstrate that tall stature and increased number of retrieved oocytes independently increase the chance of dizygotic twinning after IVF with DET.
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Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis
BACKGROUND
Current non-invasive diagnostic methods for endometriosis lack sensitivity and specificity. In search for new diagnostic biomarkers for ovarian endometriosis, we used a hypothesis-generating targeted metabolomics approach.
METHODS
In a case–control study, we collected plasma of study participants and analysed their metabolic profiles. We selected a group of 40 patients with ovarian endometriosis who underwent laparoscopic surgery and a control group of 52 healthy women who underwent sterilization at the University Clinical Centre Ljubljana, Slovenia. Over 140 targeted analytes included glycerophospholipids, sphingolipids and acylcarnitines. The analytes were quantified by electrospray ionization tandem mass spectrometry. For assessing the strength of association between the metabolite or metabolite ratios and the disease, we used crude and adjusted odds ratios. A stepwise logistic regression procedure was used for selecting the best combination of biomarkers.
RESULTS
Eight lipid metabolites were identified as endometriosis-associated biomarkers due to elevated levels in patients compared with controls. A model containing hydroxysphingomyelin SMOH C16:1 and the ratio between phosphatidylcholine PCaa C36:2 to ether-phospholipid PCae C34:2, adjusted for the effect of age and the BMI, resulted in a sensitivity of 90.0%, a specificity of 84.3% and a ratio of the positive likelihood ratio to the negative likelihood ratio of 48.3.
CONCLUSIONS
Our results suggest that endometriosis is associated with elevated levels of sphingomyelins and phosphatidylcholines, which might contribute to the suppression of apoptosis and affect lipid-associated signalling pathways. Our findings suggest novel potential routes for therapy by specifically blocking highly up-regulated isoforms of phosphpolipase A2 and lysophosphatidylcholine acyltransferase 4.
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