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- Stormlund, S., et al.
(författare)
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Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 370
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Tidskriftsartikel (refereegranskat)abstract
- 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) v 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.
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| 2. |
- Stormlund, S., et al.
(författare)
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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
- 2017
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- 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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article).
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| 3. |
- Vexö, LE, et al.
(författare)
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Low-grade inflammation is negatively associated with live birth in women undergoing IVF
- 2023
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Ingår i: Reproductive Biomedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 46:2, s. 302-311
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Tidskriftsartikel (refereegranskat)abstract
- Research question: Is low-grade inflammation, detected by C-reactive protein (CRP), a marker of IVF outcome addressing both blastocyst quality and pregnancy outcome? Design: This sub-study of a multicentre randomized controlled trial included 440 women undergoing IVF treatment with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Serum CRP was measured on cycle day 2-3 (baseline) and on the day of ovulation triggering. The association between CRP concentrations and reproductive outcomes (number of retrieved oocytes, number of good-quality blastocysts, pregnancy, pregnancy loss and live birth), were analysed, adjusting for relevant confounders. Results: A negative association was found between higher baseline CRP concentrations and live birth rate (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62-0.96, P = 0.02) and higher CRP concentrations at baseline were associated with pregnancy loss among women who conceived (OR 1.37, 95% CI 1.07-1.76, P = 0.01). When testing for a specific cut-off, CRP concentrations above 2.34 (the highest quartile) were more likely to be associated with pregnancy loss (P = 0.02) and a lower chance of live birth (P = 0.04) compared with the lowest quartile. No associations were found between CRP concentrations and pregnancy outcomes on the day of ovulation triggering, and there were no associations between CRP concentrations and the number of good-quality blastocysts. Conclusions: Higher CRP concentrations at cycle day 2-3, before starting ovarian stimulation, are negatively associated with chance of live birth, possibly because of an increased risk of pregnancy loss. No association was found between the number of good-quality blastocysts and CRP concentration. More studies are needed to investigate the impact of low-grade inflammation.
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| 4. |
- Alexopoulou, E., et al.
(författare)
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Embryo Morphokinetics and Blastocyst Development After GnRH Agonist versus hCG Triggering in Normo-ovulatory Women: a Secondary Analysis of a Multicenter Randomized Controlled Trial
- 2021
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 28, s. 2972-2981
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Tidskriftsartikel (refereegranskat)abstract
- 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
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| 5. |
- Priskorn, Lærke, et al.
(författare)
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RUBIC (ReproUnion Biobank and Infertility Cohort) : A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity
- 2021
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Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 9:6, s. 1828-1842
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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