Publications by authors named "Anne Zedeler"

16 Publications

  • Page 1 of 1

[Intrauterine inseminationwith or without ovarian stimulationis often a first-choice treatment for infertility].

Ugeskr Laeger 2021 11;183(48)

In Denmark, intrauterine insemination (IUI) with or without ovarian stimulation is a common treatment for infertility. If strict cancellation criteria are met to reduce the risk of multiple pregnancies in ovarian stimulation cycles, IUI can be considered safe, less invasive and less costly compared to in vitro fertilisation. In 2019, a total of 9,322 homologous IUIs and 8,433 IUIs using donor sperm were performed in Denmark, and 2,000 children were expected to be born after the use of IUI. Thus, in this review we conclude that IUI is an effective treatment for infertility in selected patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2021

In vitro fertilisation (IVF) versus intracytoplasmic sperm injection (ICSI) in patients without severe male factor infertility: study protocol for the randomised, controlled, multicentre trial INVICSI.

BMJ Open 2021 06 24;11(6):e051058. Epub 2021 Jun 24.

Department of Obstetrics and Gynaecology, The Fertility Clinic, Copenhagen University Hospital Hvidovre, Hvidovre Hospital, Hvidovre, Denmark.

Introduction: Over the last decades, the use of intracytoplasmic sperm injection (ICSI) has increased, even among patients without male factor infertility. The increase has happened even though there is no evidence to support that ICSI results in higher live birth rates compared with conventional in vitro fertilisation (IVF) in cases with nonmale factor infertility. The lack of robust evidence on an advantage of using ICSI over conventional IVF in these patients is problematic since ICSI is more invasive, complex and requires additional resources, time and effort. Therefore, the primary objective of the IVF versus ICSI (INVICSI) study is to determine whether ICSI is superior to standard IVF in patients without severe male factor infertility. The primary outcome measure is first live birth from fresh and frozen-thawed transfers after one stimulated cycle. Secondary outcomes include fertilisation rate, ongoing pregnancy rate, birth weight and congenital anomalies.

Methods And Analysis: This is a two-armed, multicentre, randomised, controlled trial. In total, 824 couples/women with infertility without severe male factor will be recruited and allocated randomly into two groups (IVF or ICSI) in a 1:1 ratio. Participants will be randomised in variable block sizes and stratified by trial site and age. The main inclusion criteria are (1) no prior IVF/ICSI treatment, (2) male partner sperm with an expected count of minimum 2 million progressive motile spermatozoa following density gradient purification on the day of oocyte pick up and (3) age of the woman between 18 and 42 years.

Ethics And Dissemination: The study will be performed in accordance with the ethical principles in the Helsinki Declaration. The study is approved by the Scientific Ethical Committee of the Capital Region of Denmark. Study findings will be presented, irrespectively of results at international conferences and submitted for publication in peer-reviewed journals.

Trial Registration Number: NCT04128904. Pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-051058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231059PMC
June 2021

RUBIC (ReproUnion Biobank and Infertility Cohort): A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity.

Andrology 2021 11 18;9(6):1828-1842. Epub 2021 Jun 18.

Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Background: Infertility affects 15%-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth.

Objectives: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?

Material And Methods: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/andr.13063DOI Listing
November 2021

Embryo Morphokinetics and Blastocyst Development After GnRH Agonist versus hCG Triggering in Normo-ovulatory Women: a Secondary Analysis of a Multicenter Randomized Controlled Trial.

Reprod Sci 2021 10 13;28(10):2972-2981. Epub 2021 Apr 13.

The Fertility Clinic, Department of Obstetrics and Gynecology, Copenhagen University Hospital Hvidovre, Kettegård Alle 30, DK-2650, Hvidovre, Denmark.

Gonadotropin-releasing hormone agonist (GnRHa) for final oocyte maturation, along with vitrification of all usable embryos followed by transfer in a subsequent frozen-thawed cycle, is the most effective strategy to avoid ovarian hyperstimulation syndrome (OHSS). However, less is known about the ovulation induction triggers effect on early embryo development and blastocyst formation. This study is a secondary analysis of a multicenter, randomized controlled trial, with the aim to compare embryo development in normo-ovulatory women, randomized to GnRHa or human chorionic gonadotropin (hCG) trigger. In all, 4056 retrieved oocytes were observed, 1998 from the GnRHa group (216 women) and 2058 from the hCG group (218 women). A number of retrieved oocytes, mature and fertilized oocytes, and high-quality embryos and blastocysts were similar between the groups. A sub-analysis in 250 women enrolled at the main trial site including 2073 oocytes was conducted to compare embryo morphokinetics and cleavage patterns with EmbryoScope time-lapse system. In total, 1013 oocytes were retrieved from the GnRHa group (124 women) and 1060 oocytes were retrieved from the hCG group (126 women). Morphokinetic parameters and cleavage patterns were comparable between the groups. However, embryos derived from the GnRHa group were less likely to perform rolling during their development than the embryos from the hCG trigger group (OR = 0.41 (95%CI 0.25; 0.67), p-value 0.0003). The comparable results on embryo development and utilization rates between the GnRHa and hCG triggers is of clinical relevance to professionals and infertile patients, when GnRHa trigger and freeze-all is performed to avoid OHSS development. ClinicalTrials.gov Identifier: NCT02746562.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-021-00564-9DOI Listing
October 2021

Identification of a unique epigenetic profile in women with diminished ovarian reserve.

Fertil Steril 2021 03 4;115(3):732-741. Epub 2020 Dec 4.

Department of Obstetrics and Gynaecology, Department of Reproductive Medicine, Hospital Herlev, Copenhagen University, Copenhagen, Denmark.

Objective: To investigate whether epigenetic profiles of mural granulosa cells (MGC) and leukocytes from women with diminished ovarian reserve (DOR) differ from those of women with normal or high ovarian reserve.

Design: Prospectively collected material from a multicenter cohort of women undergoing fertility treatment.

Setting: Private and university-based facilities for clinical services and research.

Patient(s): One hundred and nineteen women of various ages and ovarian reserve status (antimüllerian hormone level) who provided blood samples and MGC.

Intervention(s): None.

Main Outcome Measure(s): Measures of epigenetic aging rates from whole-genome methylation array data: DNA methylation variability, age acceleration, DNA methylation telomere length estimator (DNAmTL), and accumulation of epimutations.

Result(s): Comparison of DOR or high ovarian reserve samples to controls (normal ovarian reserve) showed differential methylation variability between DOR and normal samples at 4,199 CpGs in MGC, and 447 between high and normal (false-discovery rate < 0.05). Variable sites in MGC from DOR were enriched in regions marked with the repressive histone modification H3K27me3, and also included genes involved in folliculogenesis, such as insulin growth factor 2 (IGF2) and antimüllerian hormone (AMH). Regardless of ovarian reserve, very few signals were detected in leukocytes, and no overlaps with those in MGC were found. Furthermore, we found a higher number of epimutations in MGC from women with DOR (Kruskal-Wallis test, difference in mean = 3,485).

Conclusion(s): The somatic cells of human ovarian follicles have a distinctive epigenetic profile in women with DOR. A high frequency of epimutations suggests premature aging. Ovarian reserve status was not reflected in the leukocyte epigenetic profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2020.09.009DOI Listing
March 2021

Association between women's age and stage, morphology, and implantation of the competent blastocyst: a multicenter cohort study.

Fertil Steril 2021 03 29;115(3):646-654. Epub 2020 Oct 29.

The Fertility Unit, Aalborg University Hospital & Aalborg University, Aalborg, Denmark.

Objective: To study if the age of women undergoing assisted reproductive technology treatment associates with stage, morphology, and implantation of the competent blastocyst.

Design: Multicenter historical cohort study based on exposure (age) and outcome data (blastocyst stage and morphology and initial human chorionic gonadotrophin [hCG] rise) from women undergoing single blastocyst transfer resulting in singleton pregnancy/birth.

Setting: Sixteen private and university-based facilities.

Patient(s): In this study, 7,246 women who, between 2014 and 2018, underwent controlled ovarian stimulation (COS) or frozen-thawed embryo transfer (FET) with a single blastocyst transfer resulting in singleton pregnancy were identified. Linking data to the Danish Medical Birth Registry resulted in a total of 4,842 women with a live birth being included.

Intervention(s): None.

Main Outcome Measure(s): The competent blastocyst development stage (1-6), inner cell mass (A, B, C), trophectoderm (A, B, C), and initial serum hCG value.

Result(s): Adjusted analysis of age and stage in COS treatments showed that for every 1-year increase in age there was a 5% reduced probability of the competent blastocyst assessed as being in a high stage at transfer. Comparison between hCG values in women 18-24 years and 25-29 years in both COS and FET showed significantly lower levels in the youngest women.

Conclusion(s): The initial hCG rise was influenced by the age of the woman, with an identical pattern for hCG values in COS and FET treatments. In COS, the competent blastocyst had a reduced stage with increasing women's age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2020.08.1432DOI Listing
March 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies at Delivery in Women, Partners, and Newborns.

Obstet Gynecol 2021 01;137(1):49-55

Department of Obstetrics and Gynaecology, Copenhagen University Hospital Hvidovre, Hvidovre, the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Methods and Analysis, Statistics Denmark, Copenhagen, the Recurrent Pregnancy Loss Unit, the Capital Region, Rigshospitalet, Copenhagen University Hospital, Copenhagen, the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, the Department of Obstetrics and Gynaecology, the Fertility Clinic, Copenhagen University Hospital Hvidovre, Hvidovre, the Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre, the DNRF Center for Chromosome Stability (CCS), Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, the Fetal Medicine Unit, Department of Obstetrics and Gynaecology, Copenhagen University Hospital Hvidovre, Hvidovre, and the Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

Objective: To investigate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in parturient women, their partners, and their newborns and the association of such antibodies with obstetric and neonatal outcomes.

Methods: From April 4 to July 3, 2020, in a single university hospital in Denmark, all parturient women and their partners were invited to participate in the study, along with their newborns. Participating women and partners had a pharyngeal swab and a blood sample taken at admission; immediately after delivery, a blood sample was drawn from the umbilical cord. The swabs were analyzed for SARS-CoV-2 RNA by polymerase chain reaction, and the blood samples were analyzed for SARS-CoV-2 antibodies. Full medical history and obstetric and neonatal information were available.

Results: A total of 1,313 parturient women (72.5.% of all women admitted for delivery at the hospital in the study period), 1,188 partners, and 1,206 newborns participated in the study. The adjusted serologic prevalence was 2.6% in women and 3.5% in partners. Seventeen newborns had SARS-CoV-2 immunoglobulin G (IgG) antibodies, and none had immunoglobulin M antibodies. No associations between SARS-CoV-2 antibodies and obstetric or neonatal complications were found (eg, preterm birth, preeclampsia, cesarean delivery, Apgar score, low birth weight, umbilical arterial pH, need for continuous positive airway pressure, or neonatal admission), but statistical power to detect such differences was low. Full serologic data from 1,051 families showed an absolute risk of maternal infection of 39% if the partner had antibodies.

Conclusion: We found no association between SARS-CoV-2 infection and obstetric or neonatal complications. Sixty-seven percent of newborns delivered by mothers with antibodies had SARS-CoV-2 IgG antibodies. A limitation of our study is that we lacked statistical power to detect small but potentially meaningful differences between those with and without evidence of infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000004199DOI Listing
January 2021

Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial.

BMJ 2020 08 5;370:m2519. Epub 2020 Aug 5.

Fertility Clinic, Department of Obstetrics and Gynaecology, Hvidovre University Hospital, Hvidovre, Kettegaard Allé 30, Copenhagen DK-2650, Denmark.

Objective: To compare the ongoing pregnancy rate between a freeze-all strategy and a fresh transfer strategy in assisted reproductive technology treatment.

Design: Multicentre, randomised controlled superiority trial.

Setting: Outpatient fertility clinics at eight public hospitals in Denmark, Sweden, and Spain.

Participants: 460 women aged 18-39 years with regular menstrual cycles starting their first, second, or third treatment cycle of in vitro fertilisation or intracytoplasmic sperm injection.

Interventions: Women were randomised at baseline on cycle day 2 or 3 to one of two treatment groups: the freeze-all group (elective freezing of all embryos) who received gonadotropin releasing hormone agonist triggering and single frozen-thawed blastocyst transfer in a subsequent modified natural cycle; or the fresh transfer group who received human chorionic gonadotropin triggering and single blastocyst transfer in the fresh cycle. Women in the fresh transfer group with more than 18 follicles larger than 11 mm on the day of triggering had elective freezing of all embryos and postponement of transfer as a safety measure.

Main Outcome Measures: The primary outcome was the ongoing pregnancy rate defined as a detectable fetal heart beat after eight weeks of gestation. Secondary outcomes were live birth rate, positive human chorionic gonadotropin rate, time to pregnancy, and pregnancy related, obstetric, and neonatal complications. The primary analysis was performed according to the intention-to-treat principle.

Results: Ongoing pregnancy rate did not differ significantly between the freeze-all and fresh transfer groups (27.8% (62/223) 29.6% (68/230); risk ratio 0.98, 95% confidence interval 0.87 to 1.10, P=0.76). Additionally, no significant difference was found in the live birth rate (27.4% (61/223) for the freeze-all group and 28.7% (66/230) for the fresh transfer group; risk ratio 0.98, 95% confidence interval 0.87 to 1.10, P=0.83). No significant differences between groups were observed for positive human chorionic gonadotropin rate or pregnancy loss, and none of the women had severe ovarian hyperstimulation syndrome; only one hospital admission related to this condition occurred in the fresh transfer group. The risks of pregnancy related, obstetric, and neonatal complications did not differ between the two groups except for a higher mean birth weight after frozen blastocyst transfer and an increased risk of prematurity after fresh blastocyst transfer. Time to pregnancy was longer in the freeze-all group.

Conclusions: In women with regular menstrual cycles, a freeze-all strategy with gonadotropin releasing hormone agonist triggering for final oocyte maturation did not result in higher ongoing pregnancy and live birth rates than a fresh transfer strategy. The findings warrant caution in the indiscriminate application of a freeze-all strategy when no apparent risk of ovarian hyperstimulation syndrome is present.

Trial Registration: Clinicaltrials.gov NCT02746562.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.m2519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399608PMC
August 2020

Endometrial scratch injury with office hysteroscopy before IVF/ICSI: A randomised controlled trial.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 17;252:112-117. Epub 2020 Jun 17.

The Fertility Clinic, Hvidovre Hospital, Copenhagen University Hospital, Kettegaard Allé 30, 2650, Hvidovre, Denmark; The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Objective: Endometrial scratch injury (ESI) has been proposed to improve endometrial receptivity and thereby increase implantation rates in assisted reproductive technology (ART) treatment. ESI has been widely incorporated into clinical practice despite inconclusive evidence of its effect on reproductive outcomes. We aimed to assess pregnancy and live birth rates in subfertile women receiving ESI before IVF treatment in comparison to controls.

Study Design: This was a randomised controlled trial (RCT) with no blinding of participants, investigators or health care personnel. Women in ART treatment were allocated to either office hysteroscopy with ESI (ESI group) or no intervention (control group). In total 184 women in IVF/ICSI treatment with minimum one previous failed IVF/ICSI cycle, were included in the final analysis. The primary outcome was positive serum hCG (s-hCG). Secondary outcomes were ongoing pregnancy and live birth rate. Only per-protocol analyses were performed as all patients included at one centre had to be excluded. The trial is registered at ClinicalTrials.gov, NCT01743391.

Results: Our results showed a non-significant increase in positive s-hCG (OR 1.23, 95 % CI (0.65-2.33)), ongoing pregnancy (OR 1.52, 95 % CI (0.73-3.17)), and live birth rates (OR 1.69, 95 % CI (0.78-3.64)) per randomised woman between the ESI and the control group.

Conclusion: We observed no significant differences in positive s-hCG or other reproductive outcomes in the ESI vs. the control group. While the crude estimates of positive reproductive outcomes were higher in the ESI group, statistical significance was not reached, and the study was not powered to show smaller differences. However, data from this study will be re-evaluated in the context of an individual participant data meta-analysis (IPD-MA) of RCTs on ESI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.06.034DOI Listing
September 2020

Perinatal outcomes in 521 gestations after fresh and frozen cycles: a secondary outcome of a randomized controlled trial comparing GnRH antagonist versus GnRH agonist protocols.

Reprod Biomed Online 2019 Oct 17;39(4):659-664. Epub 2019 May 17.

The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Research Question: Are perinatal outcomes different after treatment with the gonadotrophin-releasing hormone (GnRH) antagonist versus the long GnRH agonist protocol for IVF?

Design: Perinatal outcomes were secondary outcomes in a large Phase IV, dual-centre, open-label, randomized controlled trial to compare GnRH antagonist and long GnRH agonist protocols in women <40 years undergoing their first assisted reproductive technology treatment. Women (n = 1050) were randomized in a ratio 1:1 from January 2009 to December 2013 and followed until December 2016. All fresh and frozen embryo transfer (FET) cycles from a single oocyte aspiration, resulting in a gestation (human chorionic gonadotrophin >10 IU/l) were included (n = 521). Data were analysed to compare preterm birth [PTB] (<37 weeks), very PTB (<32 weeks), low birthweight [LBW] (<2500 g) and very LBW (<1500 g) rates among singleton live births in GnRH antagonist versus agonist protocol.

Results: Similar perinatal outcomes were found after both protocols. In singletons after fresh embryo transfer, mean gestational age at delivery was 39.1 ± 2.49 versus 39.3 ± 1.90 (P = 0.67) and very PTB rates 1.9% versus 0% (P = 0.17). Mean birthweight was 3264 ± 662 g in the antagonist and 3341 ± 562 g in the agonist group (P = 0.37). LBW was found in 12.4% versus 7% (P = 0.19) and very LBW in 2.9% versus 1% (P = 0.34). In FET cycles, the perinatal outcomes were similar. Small for gestational age and large for gestational age rates were similar in both protocols for singleton live births after fresh and FET.

Conclusions: Perinatal outcomes are similar after the GnRH antagonist versus GnRH agonist protocols for IVF. The choice of the GnRH analogue in ovarian stimulation should be based solely on optimizing the chance of pregnancy and not on risks in perinatal outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2019.05.010DOI Listing
October 2019

Contribution of recruitable follicles to circulating anti-Müllerian hormone levels following maximal gonadotrophin stimulation in patients with limited ovarian reserve.

Gynecol Endocrinol 2020 Mar 6;36(3):273-276. Epub 2019 Aug 6.

Fertility Clinic, Hvidovre Hospital, Copenhagen University, Hvidovre, Denmark.

In women, the majority of anti-Müllerian hormone (AMH) measured in serum originate from small antral follicles measuring 2-10 mm. In gonadotrophin-stimulated cycles prior to assisted reproductive technology (ART), most of the recruitable follicles develop beyond 10 mm in size and thus lose their AMH secretion capacity causing declining serum AMH levels. The aim of this study was to define the residual serum AMH level after elimination of the AMH producing recruitable follicles following maximal gonadotrophin stimulation. We measured serum AMH and number of follicles according to size at several time points during a cycle of maximal gonadotrophin stimulation (fixed dose of 300 IE HP-hMG) in 107 women with low AMH (median AMH 5 pmol/L, interquartile range (IQR) 3.3-8.3). We found that AMH decreased gradually and reached a minimum level of -55.4% (95% CI -59.6; -50.7) of the baseline value four days after ovulation trigger. Our findings suggest that the residual AMH production origins from pre-antral and small antral follicles not visible by sonography and that they account for up to 40% of the circulating AMH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09513590.2019.1648414DOI Listing
March 2020

Comparing early embryo morphokinetics with time-lapse microscopy in patients with low and normal ovarian response to ovarian stimulation.

Reprod Biol 2019 Jun 30;19(2):127-132. Epub 2019 Mar 30.

Department of Obstetrics and Gynecology, The Fertility Clinic, Copenhagen University Hospital, Kettegård Alle 30, Hvidovre,2650, Denmark.

In this retrospective study, patients undergoing ovarian stimulation were allocated into two groups (47 normal responders (NR) vs 47 low responders (LR)) according to the number of aspirated oocytes and their Anti-Müllerian hormone (AMH). 171 oocytes were retrieved from the LR group and 447 oocytes from the NR group. The oocytes were studied regarding the early embryo morphokinetic parameters and cleavage stage patterns after data extraction from our EmbryoScope database. The following parameters were recorded; time of PN fading (tPNf), time to two cells (t2), three cells (t3), four cells (t4), asynchrony in 2 cell cycle (S2), fragmentation, multinucleation, direct cleavages from 1 to 3 cells, reversed cleavage, rolling and non-tetrahedral shape. Except of an indicative time difference in t3 (dif = 0.884; p-value < 0.046), the differences in timings of early cell divisions were not statistically significant when tPNf was used as a starting point and the analysis was adjusted for age. No statistically significant differences were observed for irregular cleavage patterns, multinucleation at 2-cell stage, fragmentation and non-tetrahedral shape rate at the 4-cell stage. However, the risk for multinucleation at 4-cell stage is significantly lower in low responders (OR = 0.342; p-value < 0.019). The groups did not differ regarding fertilization and cleavage rates as well as the number of embryos that fulfill the European Society of Human Reproduction and Embryology (ESHRE) criteria for top quality characteristics on Day 2. Embryos derived from patients with low ovarian response have similar morphokinetic characteristics and cleavage stage pattern as embryos from patients with normal ovarian response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.repbio.2019.03.002DOI Listing
June 2019

Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols.

Fertil Steril 2018 01 23;109(1):154-164. Epub 2017 Nov 23.

Fertility Clinic Section 455, Department of Obstetrics and Gynecology, Hvidovre University Hospital, Hvidovre, Copenhagen, Denmark.

Objective: To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH antagonist or long GnRH agonist protocol.

Design: Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing.

Setting: Fertility clinics at university hospitals.

Patient(s): Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols.

Intervention(s): Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495 women allocated to a long GnRH agonist protocol.

Main Outcome Measure(s): Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment.

Result(s): Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically.

Conclusion(s): Women in a short GnRH antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly.

Clinical Trial Registration Number: NCT00756028.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2017.09.020DOI Listing
January 2018

Comparison of a 'freeze-all' strategy including GnRH agonist trigger versus a 'fresh transfer' strategy including hCG trigger in assisted reproductive technology (ART): a study protocol for a randomised controlled trial.

BMJ Open 2017 Jul 31;7(7):e016106. Epub 2017 Jul 31.

Department of Obstetrics and Gynaecology, The Fertility Clinic, Hvidovre University Hospital, Copenhagen, Denmark.

Introduction: Pregnancy rates after frozen embryo transfer (FET) have improved in recent years and are now approaching or even exceeding those obtained after fresh embryo transfer. This is partly due to improved laboratory techniques, but may also be caused by a more physiological hormonal and endometrial environment in FET cycles. Furthermore, the risk of ovarian hyperstimulation syndrome is practically eliminated in segmentation cycles followed by FET and the use of natural cycles in FETs may be beneficial for the postimplantational conditions of fetal development. However, a freeze-all strategy is not yet implemented as standard care due to limitations of large randomised trials showing a benefit of such a strategy. Thus, there is a need to test the concept against standard care in a randomised controlled design. This study aims to compare ongoing pregnancy and live birth rates between a freeze-all strategy with gonadotropin-releasing hormone (GnRH) agonist triggering versus human chorionic gonadotropin (hCG) trigger and fresh embryo transfer in a multicentre randomised controlled trial.

Methods And Analysis: Multicentre randomised, controlled, double-blinded trial of women undergoing assisted reproductive technology treatment including 424 normo-ovulatory women aged 18-39 years from Denmark and Sweden. Participants will be randomised (1:1) to either (1) GnRH agonist trigger and single vitrified-warmed blastocyst transfer in a subsequent hCG triggered natural menstrual cycle or (2) hCG trigger and single blastocyst transfer in the fresh (stimulated) cycle. The primary endpoint is to compare ongoing pregnancy rates per randomised patient in the two treatment groups after the first single blastocyst transfer.

Ethics And Dissemination: The study will be performed in accordance with the ethical principles in the Helsinki Declaration. The study is approved by the Scientific Ethical Committees in Denmark and Sweden. The results of the study will be publically disseminated.

Trial Registration Number: NCT02746562; Pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2017-016106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642760PMC
July 2017

Predictive value of plasma human chorionic gonadotropin measured 14 days after Day-2 single embryo transfer.

Acta Obstet Gynecol Scand 2017 Aug 19;96(8):960-967. Epub 2017 May 19.

The Fertility Clinic, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.

Introduction: Prediction of pregnancy outcome after in vitro fertilization is important for patients and clinicians. Early plasma human chorionic gonadotropin (p-hCG) levels are the best known predictor of pregnancy outcome, but no studies have been restricted to single embryo transfer (SET) of Day-2 embryos. The aim of the present study was to investigate the predictive value of p-hCG measured exactly 14 days after the most commonly used Day-2 SET on pregnancy, delivery, and perinatal outcome.

Material And Methods: A retrospective analysis of prospectively collected data on 466 women who had p-hCG measured exactly 14 days after Day-2 SET during a randomized trial including 1050 unselected women (aged 18-40 years) undergoing their first in vitro fertilization/ intracytoplasmic sperm injection treatment.

Results: The p-hCG predicted clinical pregnancy [area under the curve (AUC) 0.953; 95% CI 0.915-0.992] significantly better than ongoing pregnancy (AUC 0.803, 95% CI 0.717-0.890) and delivery (AUC 0.772, 95% CI 0.691-0.854). Women with p-hCG levels in the lowest quartile had significantly lower clinical pregnancy, ongoing pregnancy, and delivery rates (p < 0.001), whereas the pregnancy outcome and post-clinical pregnancy loss remained similar throughout the three highest p-hCG quartiles. The p-hCG level was related to neither birthweight nor gestational age at delivery.

Conclusions: Clinical pregnancy is significantly better predicted by p-hCG compared with ongoing pregnancy and delivery. Clinical pregnancy rates, ongoing pregnancy rates, and delivery rates remained similar throughout the three highest p-hCG quartiles with no trend towards "the higher the better".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aogs.13144DOI Listing
August 2017

Murine leukemia virus transmembrane protein R-peptide is found in small virus core-like complexes in cells.

J Gen Virol 2006 Jun;87(Pt 6):1583-1588

Department of Pharmacology and Pharmacotherapy, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

The core of the retrovirus Murine leukemia virus (MLV) consists of the Gag precursor protein and viral RNA. It assembles at the cytoplasmic face of the cell membrane where, by an unclear mechanism, it collects viral envelope proteins embedded in the cell membrane and buds off. The C-terminal half of the short cytoplasmic tail of the envelope transmembrane protein (TM) is cleaved off to yield R-peptide and fusion-active TM. In Moloney MLV particles, R-peptide was found to bind to core particles. In cells, R-peptide and low amounts of uncleaved TM were found to be associated with small core-like complexes, i.e. mild detergent-insoluble, Gag-containing complexes with a density of 1.23 g ml(-1) and a size of 150-200 S. Our results suggest that TM associates with the assembling core particle through the R-peptide before budding and that this is the mechanism by which the budding virus acquires the envelope proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/vir.0.81527-0DOI Listing
June 2006
-->