Publications by authors named "Georg Griesinger"

91 Publications

Erratum: ESHRE guideline: ovarian stimulation for IVF/ICSI.

Hum Reprod Open 2020 29;2020(4):hoaa067. Epub 2020 Dec 29.

Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, The Netherlands.

[This corrects the article DOI: 10.1093/hropen/hoaa009.][This corrects the article DOI: 10.1093/hropen/hoaa009.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hropen/hoaa067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770487PMC
December 2020

Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: A systematic review and individual participant data meta-analysis.

PLoS One 2020 4;15(11):e0241044. Epub 2020 Nov 4.

Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.

The aim of this systematic review and meta-analysis was to conduct a comprehensive assessment of the evidence on the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) for luteal phase support. Embase and MEDLINE were searched for studies that evaluated the effect of luteal phase support with daily administration of oral dydrogesterone (20 to 40 mg) versus MVP capsules (600 to 800 mg) or gel (90 mg) on pregnancy or live birth rates in women undergoing fresh-cycle IVF (protocol registered at PROSPERO [CRD42018105949]). Individual participant data (IPD) were extracted for the primary analysis where available and aggregate data were extracted for the secondary analysis. Nine studies were eligible for inclusion; two studies had suitable IPD (full analysis sample: n = 1957). In the meta-analysis of IPD, oral dydrogesterone was associated with a significantly higher chance of ongoing pregnancy at 12 weeks of gestation (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.08 to 1.61; P = 0.0075) and live birth (OR, 1.28; 95% CI, 1.04 to 1.57; P = 0.0214) compared to MVP. A meta-analysis combining IPD and aggregate data for all nine studies also demonstrated a statistically significant difference between oral dydrogesterone and MVP (pregnancy: OR, 1.16; 95% CI, 1.01 to 1.34; P = 0.04; live birth: OR, 1.19; 95% CI, 1.03 to 1.38; P = 0.02). Safety parameters were similar between the two groups. Collectively, this study indicates that a higher pregnancy rate and live birth rate may be obtained in women receiving oral dydrogesterone versus MVP for luteal phase support.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241044PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641447PMC
December 2020

Strong variation in progesterone production of the placenta in early pregnancy - what are the clinical implications?

Reprod Biomed Online 2020 10 18;41(4):748-749. Epub 2020 Jul 18.

Department of Gynaecological Endocrinology and Reproductive Medicine, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, Luebeck 23538, Germany. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2020.07.009DOI Listing
October 2020

The performance of the Elecsys® anti-Müllerian hormone assay in predicting extremes of ovarian response to corifollitropin alfa.

Reprod Biomed Online 2020 Jul 30;41(1):29-36. Epub 2020 Apr 30.

Department of Obstetrics, Gynecology and Reproductive Medicine, Dexeus University Hospital, Department of Clinical Medicine, Faculty of Health, Aarhus University, Barcelona, Aarhus 08028, 8000, Spain, Denmark. Electronic address:

Research Question: What is the performance of anti-Müllerian hormone (AMH) as measured by the Elecsys® AMH assay in predicting ovarian response in women treated with 150 µg corifollitropin alfa (CFA)?

Design: Multicentre, prospective study conducted between December 2015 and April 2018. Women were aged 18-43 years, had regular menstrual bleeding, a body mass index of 17-35 kg/m and weighed 60 kg or over.

Exclusion Criteria: previous oophorectomy, history of ovarian hyperstimulation syndrome, a previous IVF and intracytoplasmic sperm injection cycle producing over 30 follicles measuring 11 mm or wider, basal antral follicle count (AFC) over 20 or polycystic ovarian syndrome. All women were treated with 150 μg CFA followed by recombinant FSH (150-300 IU/day) in a fixed gonadotrophin releasing hormone antagonist protocol.

Results: Of the 219 patients enrolled, 22.8% had low ovarian response (three or fewer oocytes), 66.2% had normal response and 11% had high ovarian response (15 or more oocytes). The AMH and AFC presented an area under the curve of 0.883 (95% CI 0.830 to 0.936) and 0.879 (95% CI 0.826 to 0.930), respectively, for low ovarian response; and an AUC of 0.865 (95% CI 0.793 to 0.935) and 0.822 (95% CI 0.734 to 0.909) for high ovarian response. An AMH cut-off of 1.0 ng/ml provided a sensitivity of 92.0% and a specificity of 66.9% in the prediction of low ovarian response; a cut-off of 2.25 ng/ml predicted high ovarian response with a sensitivity of 54.2% and a specificity of 91.8%.

Conclusions: The automated Elecsys® AMH assay predicts ovarian response in a CFA antagonist protocol. The best predictors of ovarian response in CFA-treated patients were AMH and AFC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2020.03.023DOI Listing
July 2020

ESHRE guideline: ovarian stimulation for IVF/ICSI.

Hum Reprod Open 2020 1;2020(2):hoaa009. Epub 2020 May 1.

Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands.

Study Question: What is the recommended management of ovarian stimulation, based on the best available evidence in the literature?

Summary Answer: The guideline development group formulated 84 recommendations answering 18 key questions on ovarian stimulation.

What Is Known Already: Ovarian stimulation for IVF/ICSI has been discussed briefly in the National Institute for Health and Care Excellence guideline on fertility problems, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologist has published a statement on ovarian stimulation in assisted reproduction. There are, to our knowledge, no evidence-based guidelines dedicated to the process of ovarian stimulation.

Study Design Size Duration: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 8 November 2018 and written in English were included. The critical outcomes for this guideline were efficacy in terms of cumulative live birth rate per started cycle or live birth rate per started cycle, as well as safety in terms of the rate of occurrence of moderate and/or severe ovarian hyperstimulation syndrome (OHSS).

Participants/materials Setting Methods: Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.

Main Results And The Role Of Chance: The guideline provides 84 recommendations: 7 recommendations on pre-stimulation management, 40 recommendations on LH suppression and gonadotrophin stimulation, 11 recommendations on monitoring during ovarian stimulation, 18 recommendations on triggering of final oocyte maturation and luteal support and 8 recommendations on the prevention of OHSS. These include 61 evidence-based recommendations-of which only 21 were formulated as strong recommendations-and 19 good practice points and 4 research-only recommendations. The guideline includes a strong recommendation for the use of either antral follicle count or anti-Müllerian hormone (instead of other ovarian reserve tests) to predict high and poor response to ovarian stimulation. The guideline also includes a strong recommendation for the use of the GnRH antagonist protocol over the GnRH agonist protocols in the general IVF/ICSI population, based on the comparable efficacy and higher safety. For predicted poor responders, GnRH antagonists and GnRH agonists are equally recommended. With regards to hormone pre-treatment and other adjuvant treatments (metformin, growth hormone (GH), testosterone, dehydroepiandrosterone, aspirin and sildenafil), the guideline group concluded that none are recommended for increasing efficacy or safety.

Limitations Reason For Caution: Several newer interventions are not well studied yet. For most of these interventions, a recommendation against the intervention or a research-only recommendation was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.

Wider Implications Of The Findings: The guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available. In addition, a list of research recommendations is provided to promote further studies in ovarian stimulation.

Study Funding/competing Interests: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. F.B. reports research grant from Ferring and consulting fees from Merck, Ferring, Gedeon Richter and speaker's fees from Merck. N.P. reports research grants from Ferring, MSD, Roche Diagnositics, Theramex and Besins Healthcare; consulting fees from MSD, Ferring and IBSA; and speaker's fees from Ferring, MSD, Merck Serono, IBSA, Theramex, Besins Healthcare, Gedeon Richter and Roche Diagnostics. A.L.M reports research grants from Ferring, MSD, IBSA, Merck Serono, Gedeon Richter and TEVA and consulting fees from Roche, Beckman-Coulter. G.G. reports consulting fees from MSD, Ferring, Merck Serono, IBSA, Finox, Theramex, Gedeon-Richter, Glycotope, Abbott, Vitrolife, Biosilu, ReprodWissen, Obseva and PregLem and speaker's fees from MSD, Ferring, Merck Serono, IBSA, Finox, TEVA, Gedeon Richter, Glycotope, Abbott, Vitrolife and Biosilu. E.B. reports research grants from Gedeon Richter; consulting and speaker's fees from MSD, Ferring, Abbot, Gedeon Richter, Merck Serono, Roche Diagnostics and IBSA; and ownership interest from IVI-RMS Valencia. P.H. reports research grants from Gedeon Richter, Merck, IBSA and Ferring and speaker's fees from MSD, IBSA, Merck and Gedeon Richter. J.U. reports speaker's fees from IBSA and Ferring. N.M. reports research grants from MSD, Merck and IBSA; consulting fees from MSD, Merck, IBSA and Ferring and speaker's fees from MSD, Merck, IBSA, Gedeon Richter and Theramex. M.G. reports speaker's fees from Merck Serono, Ferring, Gedeon Richter and MSD. S.K.S. reports speaker's fees from Merck, MSD, Ferring and Pharmasure. E.K. reports speaker's fees from Merck Serono, Angellini Pharma and MSD. M.K. reports speaker's fees from Ferring. T.T. reports speaker's fees from Merck, MSD and MLD. The other authors report no conflicts of interest.

Disclaimer: . . www.eshre.eu/guidelines.ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hropen/hoaa009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203749PMC
May 2020

Is progress in clinical reproductive medicine happening fast enough?

Authors:
Georg Griesinger

Ups J Med Sci 2020 May 4;125(2):65-67. Epub 2020 May 4.

Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital of Schleswig-Holstein, Lübeck, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03009734.2020.1734991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720956PMC
May 2020

Characterization of early pregnancy placental progesterone production by use of dydrogesterone in programmed frozen-thawed embryo transfer cycles.

Reprod Biomed Online 2020 May 31;40(5):743-751. Epub 2020 Jan 31.

Department of Gynaecological Endocrinology and Reproductive Medicine, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, Luebeck 23538, Germany. Electronic address:

Research Question: When and how does the gradual transition of the endocrine control of early pregnancy from the corpus luteum to the placenta, termed luteoplacental shift, take place?

Design: Prospective analysis of serum progesterone levels in pregnancies (n = 88) resulting from programmed frozen-thawed embryo transfer cycles in which ovulation was suppressed and no corpus luteum was present. Dydrogesterone, which does not cross-react with progesterone in immunoassay or spectrometric assay, was used for luteal phase and early pregnancy support. Progesterone, oestradiol and hCG were measured at regular intervals from before pregnancy achievement until +65 to 71 days after embryo transfer by Roche Elecsys electrochemiluminescence immunoassay (Elecsys ECLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: Serum progesterone remained at baseline levels on first blood analysis +9 to 15 days after embryo transfer and increased only marginally independently from the type of pregnancy up to +16 to 22 days after embryo transfer. From +23 to 29 days after embryo transfer, progesterone increased non-linearly above 1.0 ng/ml and increased further throughout the first trimester with elevated levels in multiples. Oestradiol levels increased in parallel with progesterone; hCG plateaued around +37 to 43 days. Progesterone levels were significant predictors for pregnancy viability from +23 to 29 days after embryo transfer onwards with best accuracy +37 to 43 days after embryo transfer (receiver operator characteristic analysis area under the curve 0.98; 95% CI 0.94 to 1; P = 0.0009).

Conclusions: The onset of substantial progesterone production is the 7th gestational week. Progesterone increase is non-linear, depends on chorionicity and zygosity, and may have predictive potential on the outcome of pregnancies originating from frozen embryo transfer cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2020.01.019DOI Listing
May 2020

An Economic Analysis of Aneuploidy Screening of Oocytes in Assisted Reproduction in Germany.

Geburtshilfe Frauenheilkd 2020 Feb 21;80(2):172-178. Epub 2020 Feb 21.

Sektion für gynäkologische Endokrinologie und Reproduktionsmedizin, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

The randomized ESTEEM trial reported that preimplantation genetic aneuploidy testing of oocytes by polar body biopsy (PGT-A) with array comparative genomic hybridization (aCGH) in women aged 36 - 40 years undergoing assisted reproduction treatment reduces the number of embryo transfers and the risk of miscarriage while not impacting the live birth rate. A decision tree model based on data from the ESTEEM trial was created and analyzed, using three cost scenarios for assisted reproduction treatment in Germany (statutory health insurance [GKV] = the deductible is 50% of the standard medical costs; private medical insurance [PKV] = invoicing is based on the German medical fee schedule [GOÄ]; private medical insurance with a simple GOÄ factor [simple GOÄ factor] = invoicing is based on the standard medical fees multiplied by a linear GOÄ factor). The scenarios were compared for cost-effectiveness (cost per live birth), cost per prevented miscarriage and the threshold values for cost and effectiveness. PGT-A increased the costs per live birth in all scenarios (GKV: + 208%; PKV: + 49%; simple GOÄ factor: + 89%). A threshold analysis showed a substantial cost discrepancy between the actual cost of the intervention based on GOÄ (€ 5801) vs. the theoretically tolerable PGT-A cost (GKV: € 561, PKV: € 1037, single GOÄ-factor: € 743). The incremental cost per one prevented miscarriage was approximately € 70 000 - 75 000 for all cost scenarios. The use of PGT-A with aCGH in assisted reproduction cannot be recommended from a cost-effectiveness perspective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1079-5283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035128PMC
February 2020

Fully human glyco-optimized recombinant FSH (follitropin epsilon) - a randomized, comparator-controlled phase II clinical trial.

Reprod Biomed Online 2020 Feb 16;40(2):331-341. Epub 2019 Sep 16.

Fertility Center Berlin, Berlin, Germany.

Research Question: The study aimed to determine the standard treatment dose of follitropin epsilon for ovarian stimulation in the context of IVF treatment.

Design: A total of 247 women aged 18-37 years were treated with either 52.5, 75, 112.5 or 150 IU follitropin epsilon daily, or 150 IU every other day, or 150 IU follitropin alfa daily in a long gonadotrophin-releasing hormone agonist protocol. The study was performed as a randomized, assessor-blinded, comparator-controlled, six-armed phase II trial in eight fertility clinics in two European countries.

Results: The primary results were as follow. First, none of the doses of follitropin epsilon showed superiority for the main outcome measure, i.e. number of follicles ≥12 mm in size. Follitropin epsilon 75 IU produced results most similar to those of follitropin alfa 150 IU. In terms of secondary results, stronger effects of follitropin epsilon 112.5 IU compared with follitropin alfa 150 IU were seen for secondary outcome measures such as hormone concentrations (oestradiol, inhibin B and progesterone) and oocyte number.

Conclusions: Follitropin epsilon 75 IU daily results in a similar ovarian response to a standard dose of 150 IU follitropin alfa. This dose could be tested in a phase III trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2019.09.003DOI Listing
February 2020

A Phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in fertilization (Lotus II): results from the Chinese mainland subpopulation.

Gynecol Endocrinol 2020 Feb 9;36(2):175-183. Epub 2019 Aug 9.

Center for Reproductive Medicine, Shandong University, Jinan, China.

Lotus II, a randomized, open-label, multicenter, international study compared the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) gel for luteal support in IVF. A prespecified subgroup analysis was performed on 239 Chinese mainland subjects from the overall study population ( = 1034), who were randomized to oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily from the day of oocyte retrieval until 12 weeks of gestation. The aim was to demonstrate non-inferiority of oral dydrogesterone to MVP gel, assessed by the presence of a fetal heartbeat at 12 weeks of gestation. In the Chinese mainland subpopulation, there was a numerical difference of 9.4% in favor of oral dydrogesterone, with ongoing pregnancy rates at 12 weeks of gestation of 61.4% and 51.9% in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 9.4%; 95% CI: -3.4 to 22.1); in the overall population, these were 38.7% and 35%, respectively (adjusted difference, 3.7%; 95% CI: -2.3 to 9.7). In both the Chinese mainland subpopulation and the overall population, dydrogesterone had similar efficacy and safety to MVP gel. With convenient oral administration, dydrogesterone has potential to transform luteal support treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09513590.2019.1645110DOI Listing
February 2020

Introduction of a novel ELISA assay for serum AMH determination.

Clin Chem Lab Med 2019 07;57(8):e183-e185

Department of Gynaecological Endocrinology and Reproductive Medicine, University Hospital of Schleswig-Holstein, Lübeck, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2018-0855DOI Listing
July 2019

Reply: Ovarian response and its prediction are relevant.

Hum Reprod 2019 03;34(3):586-587

Department of Reproductive Medicine and Gynecological Endocrinology, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/dey380DOI Listing
March 2019

Thin Endometrium Is Also Associated With Lower Clinical Pregnancy Rate in Unstimulated Menstrual Cycles: A Study Based on Natural Cycle IVF.

Front Endocrinol (Lausanne) 2018 20;9:776. Epub 2018 Dec 20.

Division of Gynaecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital University Hospital, Bern, Switzerland.

Does the endometrial thickness (EMT) at the time of follicle aspiration correlate with the pregnancy rate in unstimulated menstrual cycles? This is a retrospective, observational single center study.105 women with regular menstrual cycles undergoing their first NC-IVF cycle with an embryo transfer were analyzed. Clinical pregnancy and live birth rates were calculated and data were adjusted for women's age, cycle day of follicle aspiration and body mass index (BMI). Age of participants was 35.0 y [32.0; 37.0]. Follicle aspiration was performed on day 14.0 [12.0; 15.0] of the cycle. Total clinical pregnancy rate was 24.8% and live birth rate 15.2% per transfer. Pregnancy rate in women with endometrial thickness ≤7 mm ( = 27) was 7.4 and 30.8% in women >7 mm ( = 78) (OR 5.56, 1.22-25.36) ( = 0.03). Live birth rates were not significantly different. Quadratic regression analysis revealed lower pregnancy rates in women with thin (around <8 mm) as well as with thick (around >11 mm) endometria. -value after crude quadratic analysis was 0.028 and after adjustment for age, day of aspiration and BMI was 0.039. Significance was not reached for live birth rates. Thin endometrium should also be considered as an independent negative prognostic factor for achieving pregnancy in women without ovarian stimulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2018.00776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306415PMC
December 2018

Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction.

Reprod Biomed Online 2019 Feb 15;38(2):249-259. Epub 2018 Dec 15.

Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.

The pharmacological and physiological profiles of progestogens used for luteal phase support during assisted reproductive technology are likely to be important in guiding clinical choice towards the most appropriate treatment option. Various micronized progesterone formulations with differing pharmacological profiles have been investigated for several purposes. Dydrogesterone, a stereoisomer of progesterone, is available in an oral form with high oral bioavailability; it has been used to treat a variety of conditions related to progesterone deficiency since the 1960s and has recently been approved for luteal phase support as part of an assisted reproductive technology treatment. The primary objective of this review is to critically analyse the clinical implications of the pharmacological and physiological properties of dydrogesterone for its uses in luteal phase support and in early pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2018.11.017DOI Listing
February 2019

Comparison of the follicular output rate after controlled ovarian stimulation with daily recombinant follicle-stimulating hormone versus corifollitropin alfa.

Eur J Obstet Gynecol Reprod Biol 2019 Jan 5;232:101-105. Epub 2018 Nov 5.

Department of Clinical Development, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address:

Objective: To compare the Follicular Output Rate (FORT) between corifollitropin alfa (CFA) and recombinant follicle-stimulating hormone (rFSH) during controlled ovarian stimulation (COS).

Study Design: This retrospective analysis compared FORT between women treated with CFA or rFSH from three clinical trials: ENGAGE (N = 1476; ages 18-36, >60 kg), ENSURE (N = 395; ages 18-36, ≤60 kg), and PURSUE (N = 1388; ages 35-42, ≥50 kg). Women underwent COS in a GnRH antagonist protocol followed by hCG trigger prior to IVF. Antral follicle count (AFC; <11 mm) and pre-ovulatory follicle count (>15 mm) were used for FORT, defined as [pre-ovulatory follicles/AFCx100].

Results: For CFA and rFSH, respectively, mean FORT (adjusted for trial and age) was 85.0 versus 76.8 (p < 0.001) in the combined cohort, 86.0 versus 75.0 in ENGAGE (p < 0.001), 96.2 versus 79.2 in ENSURE (p = 0.070), and 74.1 versus 71.2 in PURSUE (p = 0.180); mean oocyte output (oocytes retrieved/AFCx100, adjusted for age) was 121.9 versus 107.3 in ENGAGE (p = 0.001), 133.5 versus 102.3 in ENSURE (p < 0.001), and 100.6 versus 98.1 in PURSUE (p = 0.463). FORT and oocyte output were consistent with the number of metaphase II oocytes retrieved for CFA and rFSH: 10.4 versus 8.8 in ENGAGE (p < 0.001), 10.3 versus 7.6 in ENSURE (p < 0.001), and 7.5 versus 7.2 in PURSUE (p = 0.37). No differences in pregnancy rates based on FORT were observed.

Conclusions: FORT was significantly higher in CFA-stimulated cycles and accurately predicted oocyte output. No association of FORT with pregnancy likelihood was found.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2018.11.002DOI Listing
January 2019

The use of intracytoplasmic sperm injection is associated with a shift in the secondary sex ratio.

Reprod Biomed Online 2018 Dec 6;37(6):703-708. Epub 2018 Oct 6.

Department of Reproductive Medicine and Gynecological Endocrinology, as well as Medical Biometry and Statistics, Ratzeburger Allee 160, Luebeck 23538, Germany.

Research Question: What is the association between assisted reproductive technologies and human sex ratio as a proportion of male offspring at birth.

Design: A total of 59,628 singleton deliveries resulting from IVF, intracytoplasmic sperm injection (ICSI) and intrauterine insemination (IUI) or ovulation induction from 101 IVF clinics in Germany, that had been documented in a national German IVF registry, were analysed. Sex ratio after assisted reproductive technology was also compared with the sex ratio reported in the birth records of the German Federal Statistical Office.

Results: The sex ratio was 50.0% (95% CI 49.5% to 50.5%) for ICSI, 52.2% (95% CI 51.5% to 52.9%) for IVF, 52.2% (95% CI 50.9% to 53.5%) for IUI or ovulation induction and 51.3% in the national birth records, respectively. Significant differences existed across the three treatment groups (P = 6.86 × 10) as well as in pairwise comparisons between ICSI versus IVF (P = 6.88 × 10) and ICSI versus IUI or ovulation induction (P = 0.003). No difference existed between the groups IUI or ovulation induction versus IVF. Same results were also present after stratification by maternal age: IVF versus ICSI (P = 6.433 × 10), ICSI versus IUI or ovulation induction (P = 0.003), and IVF versus IUI or ovulation induction (non-significant). Compared with the national birth records, ICSI is associated with a lower sex ratio compared with the reference group (P < 0.001), whereas IVF is associated with a higher sex ratio (P = 0.015).

Conclusions: The use of ICSI is associated with an equal proportion of sexes at birth, which is not the case for IVF, IUI or ovulation induction, or natural conception. This phenomenon is not influenced by maternal age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2018.09.009DOI Listing
December 2018

Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial.

Hum Reprod 2018 12;33(12):2212-2221

Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussels, Belgium.

Study Question: Is oral dydrogesterone 30 mg daily non-inferior to 8% micronized vaginal progesterone (MVP) gel 90 mg daily for luteal phase support in IVF?

Summary Answer: Oral dydrogesterone demonstrated non-inferiority to MVP gel for the presence of fetal heartbeats at 12 weeks of gestation (non-inferiority margin 10%).

What Is Known Already: The standard of care for luteal phase support in IVF is the use of MVP; however, it is associated with vaginal irritation, discharge and poor patient compliance. Oral dydrogesterone may replace MVP as the standard of care if it is found to be efficacious with an acceptable safety profile.

Study Design, Size, Duration: Lotus II was a randomized, open-label, multicenter, Phase III, non-inferiority study conducted at 37 IVF centers in 10 countries worldwide, from August 2015 until May 2017. In total, 1034 premenopausal women (>18 to <42 years of age) undergoing IVF were randomized 1:1 (stratified by country and age group), using an Interactive Web Response System, to receive oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily.

Participants/materials, Setting, Methods: Subjects received either oral dydrogesterone (n = 520) or MVP gel (n = 514) on the day of oocyte retrieval, and luteal phase support continued until 12 weeks of gestation. The primary outcome measure was the presence of fetal heartbeats at 12 weeks of gestation, as determined by transvaginal ultrasound.

Main Results And The Role Of Chance: Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates in the full analysis sample (FAS) at 12 weeks of gestation of 38.7% (191/494) and 35.0% (171/489) in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 3.7%; 95% CI: -2.3 to 9.7). Live birth rates in the FAS of 34.4% (170/494) and 32.5% (159/489) were obtained for the oral dydrogesterone and MVP gel groups, respectively (adjusted difference 1.9%; 95% CI: -4.0 to 7.8). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP gel.

Limitations, Reasons For Caution: The analysis of the results was powered to consider the ongoing pregnancy rate, but a primary objective of greater clinical interest may have been the live birth rate. This study was open-label as it was not technically feasible to make a placebo applicator for MVP gel, which may have increased the risk of bias for the subjective endpoints reported in this study. While the use of oral dydrogesterone in fresh-cycle IVF was investigated in this study, further research is needed to investigate its efficacy in programmed frozen-thawed cycles where corpora lutea do not exist.

Wider Implications Of The Findings: This study demonstrates that oral dydrogesterone is a viable alternative to MVP gel, due to its comparable efficacy and tolerability profiles. Owing to its patient-friendly oral administration route, dydrogesterone may replace MVP as the standard of care for luteal phase support in fresh-cycle IVF.

Study Funding/competing Interests(s): This study was sponsored and supported by Abbott. G.G. has received investigator fees from Abbott during the conduct of the study. Outside of this submitted work, G.G. has received non-financial support from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope and Gedeon Richter, as well as personal fees from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope, VitroLife, NMC Healthcare, ReprodWissen, Biosilu, Gedeon Richter and ZIVA. C.B. is the President of the Belgian Society of Reproductive Medicine (unpaid) and Section Editor of Reproductive BioMedicine Online. C.B. has received grants from Ferring Pharmaceuticals, participated in an MSD sponsored trial, and has received payment from Ferring, MSD, Biomérieux, Abbott and Merck for lectures. G.S. has no conflicts of interest to be declared. A.P. is the General Secretary of the Indian Society of Assisted Reproduction (2017-2018). B.D. is President of Pune Obstetric and Gynecological Society (2017-2018). D.-Z.Y. has no conflicts of interest to be declared. Z.-J.C. has no conflicts of interest to be declared. E.K. is an employee of Abbott Laboratories GmbH, Hannover, Germany and owns shares in Abbott. C.P.-F. is an employee of Abbott GmbH & Co. KG, Wiesbaden, Germany and owns shares in Abbott. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Origio, Besins, Ferring and Mithra (now Allergan); and H.T. has received consultancy fees from Finox-Gedeon Richter, Merck, Ferring, Abbott and ObsEva.

Trial Registration Number: NCT02491437 (clinicaltrials.gov).

Trial Registration Date: 08 July 2015.

Date Of First Patient’s Enrollment: 17 August 2015.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/dey306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238366PMC
December 2018

Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial.

Hum Reprod 2018 09;33(9):1767-1776

Research Group Reproduction and Genetics, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium.

Study Question: Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis?

Summary Answer: PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years.

What Is Known Already: PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial.

Study Design, Size, Duration: This is a multinational, multicentre, pragmatic, randomized clinical trial with intention-to-treat analysis. Of 396 women enroled between June 2012 and December 2016, 205 were allocated to CCS of the first and second polar body (study group) as part of their ICSI treatment cycle and 191 were allocated to ICSI treatment without chromosome screening (control group). Block randomization was performed stratified for centre and age group. Participants and clinicians were blinded at the time of enrolment until the day after intervention.

Participants/materials, Setting, Methods: Infertile couples in which the female partner was 36-40 years old and who were scheduled to undergo ICSI treatment were eligible. In those assigned to PGT-A, array comparative genomic hybridization (aCGH) analysis of the first and second polar bodies of the fertilized oocytes was performed using the 24sure array of Illumina. If in the first treatment cycle all oocytes were aneuploid, a second treatment with PB array CGH was offered. Participants in the control arm were planned for ICSI without PGT-A. Main exclusion criteria were three or more previous unsuccessful IVF or ICSI cycles, three or more clinical miscarriages, poor response or low ovarian reserve. The primary outcome was the cumulative live birth rate after fresh or frozen embryo transfer recorded over 1 year after the start of the intervention.

Main Results And The Role Of Chance: Of the 205 participants in the chromosome screening group, 50 (24%) had a live birth with intervention within 1 year, compared to 45 of the 191 in the group without intervention (24%), a difference of 0.83% (95% CI: -7.60 to 9.18%). There were significantly fewer participants in the chromosome screening group with a transfer (relative risk (RR) = 0.81; 95% CI: 0.74-0.89) and fewer with a miscarriage (RR = 0.48; 95% CI: 0.26-0.90).

Limitations, Reasons For Caution: The targeted sample size was not reached because of suboptimal recruitment; however, the included sample allowed a 90% power to detect the targeted increase. Cumulative outcome data were limited to 1 year. Only 11 patients out of 32 with exclusively aneuploid results underwent a second treatment cycle in the chromosome screening group.

Wider Implications Of The Findings: The observation that the similarity in birth rates was achieved with fewer transfers, less cryopreservation and fewer miscarriages points to a clinical benefit of PGT-A, and this form of embryo selection may, therefore, be considered to minimize the number of interventions while producing comparable outcomes. Whether these benefits outweigh drawbacks such as the cost for the patient, the higher workload for the IVF lab and the potential effect on the children born after prolonged culture and/or cryopreservation remains to be shown.

Study Funding/competing Interest(s): This study was funded by the European Society of Human Reproduction and Embryology. Illumina provided microarrays and other consumables necessary for aCGH testing of polar bodies. M.B.'s institution (UZBrussel) has received educational grants from IBSA, Ferring, Organon, Schering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speakers' fees from Organon, Serono Symposia and Merck. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott and Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. W.V., C.S., P.M.B., V.G., G.A., M.D., T.E.G., L.G., G.Ka., G.Ko., J.L., M.C.M., M.P., A.S., M.T., K.V., J.G. and K.S. declare no conflict of interest.

Trial Registration Number: NCT01532284.

Trial Registration Date: 7 February 2012.

Date Of First Patient’s Enrolment: 25 June 2012.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/dey262DOI Listing
September 2018

Performance of prognostic modelling of high and low ovarian response to ovarian stimulation for IVF.

Hum Reprod 2018 08;33(8):1499-1505

Department of Reproductive Medicine and Gynecological Endocrinology, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, Luebeck, Germany.

Study Question: What is the performance of previously established regression models in predicting low and high ovarian response to 150 μg corifollitropin alfa/GnRH-antagonist ovarian stimulation in an independent dataset?

Summary Answer: The outcome of ovarian stimulation with 150 μg corifollitropin alfa in a fixed, multiple dose GnRH-antagonist protocol can be validly predicted using logistic regression models with AMH being of paramount importance.

What Is Known Already: Predictors of ovarian response have been identified in FSH/GnRH agonist protocols as well as ovarian stimulation with corifollitropin alfa/GnRH-antagonist. Multivariable response models have been established already, however, external validation of model performance has so far been lacking.

Study Design, Size, Duration: Data from a prospective, multi-centre (n = 5), multi-national, investigator-initiated, observational cohort study were analysed. Infertile women (n = 211), body weight >60 kg, were undergoing ovarian stimulation with 150 μg corifollitropin alfa in a GnRH-antagonist multiple dose protocol for transvaginal oocyte retrieval for IVF. Demographic, sonographic and endocrine parameters were prospectively assessed on cycle Day 2 or 3 of spontaneous menstruation before ovarian stimulation. Main outcomes were low (<6 oocytes) and high (>18 oocytes) ovarian response.

Participants/materials, Setting, Methods: Firstly, previously established prediction models for low ovarian response (LOR) and high ovarian response (HOR) were tested using the original parameters. Secondly, re-estimated parameters generated from the present data were tested on the established models. Thirdly, for the development of new predictive models of both LOR and HOR, several logistic regression models were estimated. Resulting prediction models were compared by means of the area under the receiver operating characteristic curve (AUC) and bias-corrected Akaike's Information Criterion (AICc) to identify the most reasonable model for each scenario.

Main Results And The Role Of Chance: The previously established prediction models for low and high response performed remarkably well on this dataset (low response AUC 0.8879 (95% CI: 0.8185-0.9573) and high response AUC 0.8909 (95% CI: 0.8251-0.9568)). A newly developed simplified model for LOR with log-transformed AMH values and only age as another covariate showed an AUC of 0.8920 (95% CI: 0.8237-0.9603) with the lowest AICc of all models compared. For predicting HOR, we suggest a simplified model using AMH, FSH and AFC (AUC of 0.8976, 95% CI: 0.8206-0.9746).

Limitations, Reasons For Caution: All analyses were done on data from women with a body weight >60 kg. The newly developed simplified models may suffer from overfitting and need to be tested in further independent data sets.

Wider Implications Of The Findings: Patient selection for ovarian stimulation with corifollitropin alfa should utilize established response prediction models. The clinical impact of this needs to be evaluated in future studies.

Study Funding/competing Interest(s): The study was funded by university funds. M.O.S., T.L. and I.R.K. have nothing to declare. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott, Marckryl Pharma, VitroLife, NMC Healthcare, ReprodWissen, ZIVA and BioSilu.

Trial Registration Number: Not applicable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/dey236DOI Listing
August 2018

Can a quality-of-life assessment assist in identifying women at risk of prematurely discontinuing IVF treatment? A prospective cohort study utilizing the FertiQoL questionnaire.

Arch Gynecol Obstet 2018 07 4;298(1):223-229. Epub 2018 Jun 4.

Department of Gynaecological Endocrinology and Reproductive Medicine, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

Purpose: This study aimed at assessing quality of life (QoL) by means of a validated measurement tool (FertiQoL) in German infertile patients before a first IVF/ICSI cycle with ancillary assessment of changes in FertiQoL scores after a failed first cycle and the predictive capacity of FertiQoL scores for treatment discontinuation.

Methods: The validated FertiQoL tool consisting of 24 questions regarding fertility-specific aspects of QoL was used for this prospective cohort study conducted at a university affiliated IVF center in Germany. Female patients (n = 119) filled out the FertiQoL form and questionnaire on sociodemographic variables on initiation of a first- and second-cycle IVF/ICSI treatment, respectively.

Results: On initiation of a first IVF/ICSI cycle, the mean scores (± standard deviation) for subscales emotional, mind-body, relational, and social items were 62 (± 19), 75 (± 17), 82 (± 13), and 78 (± 14), respectively; the total FertiQoL score was 73 (± 12). The mean total FertiQoL score at initiation of a first treatment cycle did not differ between patients who continued vs. discontinued treatment in case of no pregnancy achievement in the first cycle (73) (± 10) vs. 74 (± 14), p = 0.46). Furthermore, the mean total FertiQoL score did not change after an unsuccessful first IVF cycle (74 vs. 76, p = 0.46).

Conclusions: There was no statistical difference in a small sample size for FertiQoL scores between all groups. In this study, FertiQoL scores were, therefore, not usable to predict withdrawal from infertility treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-018-4797-2DOI Listing
July 2018

Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard?

Fertil Steril 2018 05;109(5):756-762

Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.

Oral dydrogesterone has been used for luteal phase support on an empirical basis since the early days of in vitro fertilization (IVF) treatment. Systematic comparisons of oral dydrogesterone with vaginal progesterone, so far considered to be the standard of care, started to appear in the middle 2000s. Recently, a large, randomized, double-blind, double-dummy phase III trial on the use of daily 30 mg oral dydrogesterone versus daily 600 mg micronized vaginal progesterone for LPS in IVF was published. This company-sponsored trial confirmed the efficacy findings from previous independent researchers and firmly established the noninferiority of daily 30 mg oral dydrogesterone for luteal phase support. Despite oral administration and first pass through the liver, dydrogesterone was as well tolerated as vaginal progesterone in safety analyses. Moreover, no new fetal safety concerns have arisen from that trial. Given the widespread preference of women for an oral compound, dydrogesterone may well become the new standard for luteal phase support in fresh embryo transfer IVF cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2018.03.034DOI Listing
May 2018

Introduction: Management of the luteal phase in assisted reproductive technology.

Fertil Steril 2018 05;109(5):747-748

Division of Reproductive Endocrinology and Infertility, Department of Reproductive Medicine, University of California, San Diego, La Jolla, California.

The increasing utilization of a gonadotropin-releasing hormone agonist ovulation trigger and the widespread use of artificial cycles for the transfer of frozen-thawed or donated embryos has renewed interest in the luteal phase in assisted reproductive technology. The "luteal phase defect" phenomenon is now understood as a continuum: there is less impairment with milder stimulation than with more intense ovarian stimulation, and less impairment after controlled ovarian stimulation and human chorionic gonadotropin ovulation triggering than after gonadotropin-releasing hormone agonist ovulation triggering, the latter being associated with rapid luteolysis. The intensity of the support of luteal phase necessary to achieve optimal outcomes therefore depends on the degree of luteal phase defect encountered in different treatment protocols. Ultimately, the luteal phase of an artificial cycle in which ovulation is suppressed, a corpus luteum is therefore absent, and the establishment of endometrial receptivity completely relies on the orchestrated exogenous administration of sex steroids, is the litmus test situation for the study of the efficacy of different luteal phase support preparations, doses, regimens, and routes of administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2018.02.009DOI Listing
May 2018

Endometrial thickness on the day of embryo transfer is a poor predictor of IVF treatment outcome.

Hum Reprod Open 2018 29;2018(1):hox031. Epub 2018 Jan 29.

IBSA Institut Biochimique SA, via del Piano, 6915 Pambio-Noranco, Switzerland.

Study Question: What is the independent contribution of endometrial thickness (EMT) on day of embryo transfer to achieving an ongoing pregnancy and live birth after IVF treatment?

Summary Answer: EMT is a poor predictor of IVF success and has only little independent prognostic value.

What Is Known Already: In a number of previous studies, pregnancy rates have been found to be lower in patients with thin endometrium.

Study Design Size Duaration: This is a retrospective analysis of data from two large, randomized phase III studies (conducted in Europe and the USA) comparing s.c. progesterone with vaginal progesterone for luteal phase support. The studies were very similar in design, patient population and outcome, and the study data were combined and analysed on an individual patient level.

Participants/materials Setting Method: Subjects were infertile patients with an indication for IVF/ICSI, aged between 18 and 42 years, BMI <30 kg/m, <3 prior ART cycles and ≥ 3 oocytes after controlled ovarian stimulation with GnRH-agonist or GnRH-antagonist. EMT was assessed on day of embryo transfer ( = 1401). The association of EMT and ongoing pregnancy rate was determined by comparison of outcomes by quantiles of EMT. The predictive capacity of EMT for ongoing pregnancy achievement was assessed at each millimeter cut-off. Finally, a regression model was built to determine the contribution of EMT among other confounders, such as age and oocyte numbers, on the likelihood of ongoing pregnancy and live birth.

Main Results And The Role Of Chance: In univariate analysis, ongoing pregnancy rates correlate to EMT. In patients above a cut-off of ≥9 mm EMT, the chance of pregnancy was higher as compared to patients with an EMT of 3-8 mm (odds ratio (OR) = 1.69, 95% CI: 1.23-2.35, = 0.001; sensitivity 88.89%, specificity 17.52%, positive predictive value 39.02%, negative predictive value 72.64% and likelihood ratio 1.08). In multivariate regression analysis, after controlling for trial, female age and oocyte numbers, EMT was a statistically significant predictor of live birth (OR = 1.05, 95% CI: 1.00-1.10; = 0.0351). If EMT indeed is an independent factor affecting outcome, this finding implies that at a baseline live birth rate of 20% an increase of 2 mm in EMT should result in an increase of the live birth rate of ~1.6%.

Limitations Reasons For Caution: The independent contribution of EMT to live birth likelihood is small and may result from (undetermined) confounding. The EMT on day of embryo transfer is usually higher as compared to the EMT on day of triggering final oocyte maturation when it is conventionally assessed during routine cycle monitoring. Furthermore, endometrial lining pattern and/or subendometrial Doppler flow have not been assessed and, accordingly, the conclusions of this work are limited to only the thickness of the endometrium.

Wider Implications Of The Findings: EMT can be ignored during cycle monitoring of the majority of IVF patients and only the extremes of EMT deserve further diagnostic work-up.

Study Funding/competing Interests: The study was supported by IBSA. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott, Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. S.T. and B.C. are employees of IBSA.

Trial Registration Number: NCT00827983 and NCT00828191 (clinicaltrials.gov).

Trial Registration Date: 23 January 2009 (NCT00827983 and NCT00828191).

Date Of First Patient’s Enrolment: January 2009 (NCT00827983 and NCT00828191).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hropen/hox031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276703PMC
January 2018

Follicular flushing in patients with poor ovarian response: a systematic review and meta-analysis.

Reprod Biomed Online 2018 Apr 29;36(4):408-415. Epub 2017 Dec 29.

Department of Gynaecological Endocrinology and Reproductive Medicine, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538, Luebeck, Germany. Electronic address:

A systematic literature review and meta-analysis was conducted to evaluate the effect of follicular flushing on clinical outcomes (primary outcome: mean number of cumulus-oocyte-complexes [COC]) in poor-response IVF patients). The bibliographic databases OvidMedline (includes Pubmed), Cochrane Library and Web of Science were searched electronically for randomized controlled trials (RCT) comparing follicular flushing with no flushing. Three RCT with a total of 210 patients could be included. The mean number of COC did not increase with flushing (weighted mean difference: -0.45 COC, 95% CI -1.14 to 0.25, I = 70%; P = 0.21; three RCT, n = 210). Mean number of metaphase II oocytes and the proportion of randomized patients having at least one COC retrieved were no different between groups. No difference was observed between groups for mean number of embryos, the proportion of randomized patients achieving embryo transfer, clinical pregnancy and live birth rates. Procedure duration was significantly increased with flushing (P = 0.0006). A positive effect of flushing on any of the investigated outcomes could not be observed in the existing literature in patients with poor ovarian response. Flushing is unlikely to significantly increase the number of oocytes, and the routine use of follicular flushing should, therefore, be scrutinized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2017.12.014DOI Listing
April 2018

Microbiota-based analysis reveals specific bacterial traits and a novel strategy for the diagnosis of infectious infertility.

PLoS One 2018 9;13(1):e0191047. Epub 2018 Jan 9.

Department of Infectious Diseases and Microbiology, University of Luebeck, Luebeck, Schleswig-Holstein, Germany.

Tubal factor infertility (TFI) accounts for more than 30% of the cases of female infertility and mostly resides from an inflammatory process triggered by an infection. Clinical appearances largely differ, and very often infections are not recognized or remain completely asymptomatic over time. Here, we characterized the microbial pattern in females diagnosed with infectious infertility (ININF) in comparison to females with non-infectious infertility (nININF), female sex workers (FSW) and healthy controls (fertile). Females diagnosed with infectious infertility differed significantly in the seroprevalence of IgG antibodies against the C. trachomatis proteins MOMP, OMP2, CPAF and HSP60 when compared to fertile females. Microbiota analysis using 16S amplicon sequencing of cervical swabs revealed significant differences between ININF and fertile controls in the relative read count of Gardnerella (10.08% vs. 5.43%). Alpha diversity varies among groups, which are characterized by community state types including Lactobacillus-dominated communities in fertile females, an increase in diversity in all the other groups and Gardnerella-dominated communities occurring more often in ININF. While all single parameters did not allow predicting infections as the cause of infertility, including C. trachomatis IgG/IgA status together with 16S rRNA gene analysis of the ten most frequent taxa a total of 93.8% of the females were correctly classified. Further studies are needed to unravel the impact of the cervical microbiota in the pathogenesis of infectious infertility and its potential for identifying females at risk earlier in life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191047PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760088PMC
February 2018

GnRH antagonists vs. long GnRH agonists in IVF: significant flaws in a meta-analysis lead to invalid conclusions.

Hum Reprod Update 2018 Mar;24(2):242-243

Women's and Children's Health, UNSW Medicine, University of New South Wales, Royal Hospital for Women, Level 1, Barker Str, Randwick NSW 2031, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humupd/dmx037DOI Listing
March 2018

What is the net effect of introducing vitrification for cryopreservation of surplus 2PN oocytes in an IVF program?

Arch Gynecol Obstet 2018 02 11;297(2):529-537. Epub 2017 Dec 11.

Department of Gynecological Endocrinology and Reproductive Medicine and Universitaeres Kinderwunschzentrum Luebeck, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538, Luebeck, Germany.

Purpose: The aim of this study was to accurately describe outcome differences (cryo-survival, pregnancy rate and live birth rate, both per ET and cumulatively), between the vitrification method and slow-freezing method of surplus 2PN oocytes in an IVF program.

Methods: In 2004, the freezing method for 2PN oocytes was changed from slow-cooling to vitrification. The data of 711 patients (timespan: 1/1999-7/2011; 410 vitrification and 301 slow-cooling events) undergoing a first IVF/ICSI cycles with freezing of 2PN oocytes were retrospectively analyzed. The outcome of one, the first, IVF cycle per patient was explored. The data were analyzed per freezing-thawing attempt as well as cumulatively per one complete IVF cycle, taking pregnancy occurrence after a fresh embryo transfer preceding the cryo-cycle(s) and other confounders (such as female age, elective vs. surplus 2PN cryopreservation) into account by means of exploratory regression analyses.

Results: In the vitrification and slow-cooling group, 756 and 376, respectively, attempts of thawing 2PN oocytes were recorded. Each attempt of thawing 2PN oocytes showed statistically significantly higher mean cryo-survival rates after vitrification (effect size approximately 30-40%, with vitrification cryo-survival consistently above 90% in all thawing attempts). Furthermore, the incidence of "zero survival" was lower after vitrification (0.5 vs. 7.3%, p < 0.01). It is estimated that the odds of achieving a live birth per one IVF cycle (fresh and frozen transfers combined) with vitrification of 2PN oocytes is increased approximately 1.4-fold (OR of 1.405, 95% CI 0.968-2.038; p = 0.07); however, statistical significance was not achieved due to sample size. Female age and elective cryopreservation of all 2PN oocytes without a fresh transfer (e.g., hyperresponders) were found to be negatively and positively, respectively, associated with the chance of achieving a live birth.

Conclusions: The introduction of vitrification has a measurable impact on the efficacy of an IVF program. However, this effect is not large despite the impressively higher cryo-survival rates with vitrification. The "true" net efficacy effect of introducing 2PN vitrification in an IVF program will, in real life, be lower due to patients not having surplus 2PN oocytes available for freezing and later transfer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-017-4606-3DOI Listing
February 2018