Publications by authors named "Efstratios M Kolibianakis"

85 Publications

How frequent is severe ovarian hyperstimulation syndrome after GnRH agonist triggering in high-risk women? A systematic review and meta-analysis.

Reprod Biomed Online 2021 Mar 28;42(3):635-650. Epub 2020 Nov 28.

Unit for Human Reproduction, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki Thessaloniki, Greece. Electronic address:

The aim of the present systematic review and meta-analysis was to assess the incidence of severe ovarian hyperstimulation syndrome (OHSS) after triggering of final oocyte maturation with gonadotrophin releasing hormone agonist (GnRHa) in high-risk women. The pooled incidence of severe OHSS in high-risk women who did not receive any form of luteal phase support was 0% (95% CI 0.0 to 0.0, I = 0%, random-effects model, 14 data sets, 983 women). The pooled incidence of severe OHSS in high-risk women in whom HCG was added to standard luteal phase support was 1% (95% CI 0.0 to 2.0, I = 27.02%, random-effects model, 10 data sets, 707 women). The incidence of severe OHSS in high-risk women triggered by a combination of GnRHa and HCG (dual triggering), who received standard luteal phase support, was 1% (95% CI 0.0 to 3.0, one study, 182 women). The incidence of severe OHSS in high-risk women, is not eliminated when HCG is administered either concomitantly with GnRHa (dual triggering), during the luteal phase after GnRHa triggering, or both. On the contrary, it is eliminated when no luteal support is administered.
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http://dx.doi.org/10.1016/j.rbmo.2020.11.008DOI Listing
March 2021

Is there an optimal number of oocytes retrieved at which live birth rates or cumulative live birth rates per aspiration are maximized after ART? A systematic review.

Reprod Biomed Online 2021 Jan 22;42(1):83-104. Epub 2020 Oct 22.

National Perinatal Epidemiology and Statistics Unit, School of Women and Children's Health and Centre for Big Data Research in Health, UNSW Medicine, Level 2, AGSM Building (G27), UNSW Australia, UNSW Sydney NSW 2052, Sydney NSW, Australia; School of Women's and Children's Health, UNSW Medicine, Sydney NSW, Australia; IVFAustralia, Sydney NSW, Australia. Electronic address:

The association between the number of oocytes retrieved and fresh live birth rate (LBR) or cumulative LBR (CLBR), and whether an optimal number of oocytes are retrieved when LBR or CLBR are maximized, are highly relevant clinical questions; however published results are conflicting. A systematic review of all eligible studies (n = 16) published until January 2020 on MEDLINE, Embase, Scopus, CINAHL and Web of Science was conducted. Five studies evaluated only LBR from fresh cycles, five studies evaluated only CLBR from stimulated cycles and six evaluated both. A marked difference was observed between the oocyte yields at which LBR and CLBR were reportedly maximized in the individual studies. On the basis of nine studies, the optimal number of oocytes at which fresh LBR seems to be maximized is proposed to be between 12 and 18 oocytes (15 oocytes was the most common suggestion). On the other hand, CLBR continues to increase with the number of oocytes retrieved. This is the first systematic review on the topic, and it suggests that the retrieval of 12-18 oocytes is associated with maximal fresh LBR, whereas a continuing positive association is present between the number of oocytes retrieved and CLBR.
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http://dx.doi.org/10.1016/j.rbmo.2020.10.008DOI Listing
January 2021

Expression of genes that regulate follicle development and maturation during ovarian stimulation in poor responders.

Reprod Biomed Online 2021 Jan 25;42(1):248-259. Epub 2020 May 25.

Unit for Human Reproduction, Laboratory of Genetics, 1st Department of Obstetrics and Gynaecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Ring Road, Nea Efkarpia Thessaloniki 56403, Greece.

Research Question: Sex hormone-binding globulin (SHBG), androgen receptor (AR), LH beta polypeptide (LHB), progesterone receptor membrane component 1 (PGRMC1) and progesterone receptor membrane component 2 (PGRMC2) regulate follicle development and maturation. Their mRNA expression was assessed in peripheral blood mononuclear cells (PBMC) of normal and poor responders, during ovarian stimulation.

Design: Fifty-two normal responders and 15 poor responders according to the Bologna criteria were enrolled for IVF and intracytoplasmic sperm injection and stimulated with 200 IU of follitrophin alpha and gonadotrophin-releasing hormone antagonist. HCG was administered for final oocyte maturation. On days 1, 6 and 10 of stimulation, blood samples were obtained, serum hormone levels were measured, RNA was extracted from PBMC and real-time polymerase chain reaction was carried out to identify the mRNA levels. Relative mRNA expression of each gene was calculated by the comparative 2 method.

Results: Differences between mRNA levels of each gene on the same time point between the two groups were not significant. PGRMC1 and PGRMC2 mRNA levels were downregulated, adjusted for ovarian response and age. Positive correlations between PGRMC1 and AR (standardized beta = 0.890, P < 0.001) from day 1 to 6 and PGRMC1 and LHB (standardized beta = 0.806, P < 0.001) from day 1 to 10 were found in poor responders. PGRMC1 and PGRMC2 were positively correlated on days 6 and 10 in normal responders.

Conclusions: PGRMC1 and PGRMC2 mRNA are significantly decreased during ovarian stimulation, with some potential differences between normal and poor responders.
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http://dx.doi.org/10.1016/j.rbmo.2020.05.012DOI Listing
January 2021

Female Infertility and Cardiovascular Risk - A Hype or an Underestimated Reality?

Curr Pharm Des 2020 ;26(43):5551-5555

Unit for Human Reproduction, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Infertility may be an early indicator of later-life health risk development, such as cardiovascular disease (CVD), the leading cause of death globally. Various infertility-associated factors such as female age, polycystic ovarian syndrome, endometriosis and metabolic syndrome are also risk factors for CVD. Whether there is a real association between female infertility and CVD, given that common pathways lead to both entities, or since both female infertility and CVD share a common basis, needs to be further investigated. If such an association is confirmed, infertile women might benefit from the initiation of preventive strategies aiming to control CVD risk factors. Thus, female infertility may represent an early indicator of future CVD and concomitantly a unique opportunity to identify women at increased risk for developing CVD. It is therefore imperative that large population- based studies are performed to elucidate this issue further and promote public awareness, if necessary.
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http://dx.doi.org/10.2174/1381612826666200821114552DOI Listing
April 2021

Risk of gestational diabetes mellitus in women achieving singleton pregnancy spontaneously or after ART: a systematic review and meta-analysis.

Hum Reprod Update 2020 06;26(4):514-544

Unit for Human Reproduction, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Women who achieve pregnancy by ART show an increased risk of obstetric and perinatal complications compared with those with spontaneous conception (SC).

Objective And Rationale: The purpose of this systematic review and meta-analysis was to synthesize the best available evidence regarding the association between ART and gestational diabetes mellitus (GDM) in women with singleton pregnancies. The research question asked was whether the risk of GDM is higher in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously.

Search Methods: A literature search, in MEDLINE, Scopus and Cochrane databases, covering the period 1978-2019, was performed aiming to identify studies comparing the risk of GDM in singleton pregnancies after ART versus after SC. Both matched and unmatched studies were considered eligible. Meta-analysis of weighted data was performed using the random effects model. Results were reported as risk ratio (RR) with 95% CI. Heterogeneity was quantified with the I2 index.

Outcomes: The study reports on 63 760 women who achieved a singleton pregnancy after ART (GDM was present in 4776) and 1 870 734 women who achieved a singleton pregnancy spontaneously (GDM in 158 526). Women with singleton pregnancy achieved by ART showed a higher risk of GDM compared with those with singleton pregnancy achieved spontaneously (RR 1.53, 95% CI 1.39-1.69; I2 78.6%, n = 37, 1 893 599 women). The direction or the magnitude of the effect observed did not change in subgroup analysis based on whether the study was matched (n = 17) or unmatched (n = 20) (matched: RR 1.42, 95% CI 1.17-1.72; I2 61.5%-unmatched: RR 1.58, 95% CI 1.40-1.78; I2 84.1%) or whether it was prospective (n = 12) or retrospective (n = 25) (prospective studies: RR 1.52, 95% CI 1.27-1.83, I2 62.2%-retrospective studies: RR 1.53, 95% CI 1.36-1.72, I2 82.5%). Regarding the method of fertilization, a higher risk of GDM after ART versus SC was observed after IVF (n = 7), but not after ICSI (n = 6), (IVF: RR 1.95, 95% CI 1.56-2.44, I2 43.1%-ICSI: RR 1.42, 95% CI 0.94-2.15, I2 73.5%). Moreover, regarding the type of embryo transfer (ET), a higher risk of GDM after ART versus SC was observed after fresh (n = 14) but not after frozen (n = 3) ET (fresh ET: RR 1.38, 95% CI 1.03-1.85, I2 75.4%-frozen ET: RR 0.46, 95% CI 0.10-2.19; I2 73.1%). A higher risk of GDM was observed after ART regardless of whether the eligible studies included patients with polycystic ovary syndrome (RR 1.49, 95% CI 1.33-1.66, I2 75.0%) or not (RR 4.12, 95% CI 2.63-6.45, I2 0%), or whether this information was unclear (RR 1.46, 95% CI 1.22-1.75, I2 77.7%).

Wider Implications: The present systematic review and meta-analysis, by analysing 1 893 599 women, showed a higher risk of GDM in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously. This finding highlights the importance of early detection of GDM in women treated by ART that could lead to timely and effective interventions, prior to ART as well as during early pregnancy.
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http://dx.doi.org/10.1093/humupd/dmaa011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317285PMC
June 2020

Association between vitamin D and endometriosis: a systematic review.

Hormones (Athens) 2020 Jun 21;19(2):109-121. Epub 2019 Dec 21.

Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Endometriosis is one of the most common gynecological diseases of reproductive age, with a prevalence of 5-10% and grave consequences for quality of life and fertility. Vitamin D (vit D), a classic regulator of plasma calcium concentration and skeleton mineralization, is also an effective modulator of the immune system. Several studies suggest that immunologic properties attributed to vit D along with vit D receptor (VDR) expression in reproductive tissues may be involved in the pathogenesis of endometriosis.

Objective: To systematically review the literature for the association between components of vit D metabolism and endometriosis.

Materials And Methods: A systematic review of the literature published in the Medline and Cochrane Central databases was conducted for original research articles on humans, published in any language.

Results: Twenty-one studies were included in the systematic review. Among them, 12 examined the relationship of endometriosis with vit D metabolites, eight with vit D-binding protein (VDBP), three with VDR polymorphisms, and two with vit D regulatory enzymes. There are discrepancies between the outcomes of the available literature publications.

Conclusions: This is a systematic attempt to collect, evaluate, and present the known data on the association between vit D and endometriosis. Given the heterogeneity and the diversity of the present studies, more research is required to elucidate the association between vit D and endometriosis.
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http://dx.doi.org/10.1007/s42000-019-00166-wDOI Listing
June 2020

Association between body mass index and oocyte maturation in patients triggered with GnRH agonist who are at high risk for severe ovarian hyperstimulation syndrome: an observational cohort study.

Reprod Biomed Online 2020 Jan 15;40(1):168-175. Epub 2019 Oct 15.

Unit of Human Reproduction, 1st Department of OB/Gyn, Medical school, Aristotle University, Thessaloniki, 7 Ventiri Street, Athens 11528, Greece.

Research Question: Is body-mass index (BMI) associated with oocyte maturation in women at high risk for developing severe ovarian hyperstimulation syndrome (OHSS) who are triggered with gonadotrophin releasing hormone (GnRH) agonist?

Design: Prospective observational cohort study. A total of 113 patients at high risk for severe OHSS (presence of at least 19 follicles ≥11 mm) pre-treated with gonadotrophin releasing hormone (GnRH) antagonists and recombinant FSH were administered 0.2 mg triptorelin to trigger final oocyte maturation. Patients were classified in two groups depending on their BMI: ΒΜΙ less than 25 kg/m (n = 72) and ΒΜΙ 25 kg/m or over (n = 41). Baseline, ovarian stimulation and embryological characteristics, as well as luteal-phase hormone profiles, were compared in patients classified into the two BMI groups. The main outcome measure was the number of mature oocytes.

Results: A significantly higher number of mature (metaphase II) oocytes (19 [18-21] versus 16 [13-20], P = 0.029) was present in women with BMI less than 25 kg/m compared with those with BMI 25 kg/m or greater. The number of retrieved oocytes, the number of fertilized oocytes, oocyte retrieval, maturation and fertilization rates were similar in the two groups. A significantly higher dose of recombinant FSH was required for patients with BMI 25 kg/m or greater compared with patients with BMI less than 25 kg/m (1875 [1650-2150] IU versus 1650 [1600-1750] IU, P = 0.003) and the two groups displayed different luteal phase hormonal profiles.

Conclusions: Among women at high risk for developing severe OHSS who are triggered with a standard dose (0.2 mg) of the GnRH agonist triptorelin, women with BMI 25 kg/m or greater had significantly fewer mature oocytes, required a higher total dose of recombinant FSH compared with women with BMI less than 25 kg/m.
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http://dx.doi.org/10.1016/j.rbmo.2019.10.006DOI Listing
January 2020

Addition of procyanidine to semen preserves progressive sperm motility up to three hours of incubation.

Reprod Biol 2019 Sep 26;19(3):255-260. Epub 2019 Jul 26.

Unit for Human Reproduction, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Several studies on semen physiology and sperm fertilizing capacity have shown a beneficial effect of antioxidants. Procyanidine is a natural antioxidant, more efficient compared with vitamin C and E, with many applications in the food, agriculture, pharmaceutical and cosmetic industry. Thus, we tested whether the addition of procyanidine to the semen of infertile men has a beneficial effect on spermatozoa during their in vitro incubation and during the cryopreservation process. Semen samples of 25 infertile men were divided in to two aliquots, in which procyanidine was added or not. Semen analysis, measurement of sperm DNA fragmentation index (DFI) and measurement of reactive oxygen species (ROS) were performed 3 h after incubation at 37 °C and after sperm cryopreservation and thawing. In-vitro addition of procyanidine to semen of infertile men resulted in a lesser decrease in progressive motility [-4 (-31:+6) vs. -6 (-31:+5), p < 0.001] and total motility [-5 (-29:+3) vs. -9 (-32:+2), p < 0.001] after 3 h of incubation compared with no addition of procyanidine. Sperm morphology was decreased only in the control group after 3 h of incubation [2 (0:+6) vs. 1 (0:+4), p = 0.009]. Furthermore, a larger increase in sperm DFI was observed in the control compared with the procyanidine group [9 (-7:+27) vs. 3 (-3:+18), p = 0.005] after thawing of cryopreserved semen samples. In conclusion, in-vitro addition of procyanidine to the semen of infertile men exerts a protective effect on progressive motility during handling and after 3 h of incubation as well as on sperm DFI during the process of cryopreservation.
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http://dx.doi.org/10.1016/j.repbio.2019.07.001DOI Listing
September 2019

Vitamin D and Obesity: Two Interacting Players in the Field of Infertility.

Nutrients 2019 Jun 27;11(7). Epub 2019 Jun 27.

Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.

Obesity plays an important role in human fertility in both genders. The same is true for vitamin D, for which accumulating evidence from observational human studies suggests a key role for both male and female fertility. In the latter case, however, robust data from relevant interventional studies are currently lacking. It is also not clear whether obesity and vitamin D deficiency, besides their independent effect on human infertility, act in synergy. Several pathogenetic mechanisms may be proposed as a linkage between vitamin D deficiency and obesity, with respect to infertility. In any case, the independent contribution of vitamin D deficiency in obese infertile states needs to be proven in interventional studies focusing on either vitamin D supplementation in obese or weight loss strategies in vitamin D-deficient infertile patients.
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http://dx.doi.org/10.3390/nu11071455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683323PMC
June 2019

Egg freezing and late motherhood.

Maturitas 2019 Jul 29;125:1-4. Epub 2019 Mar 29.

Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Egg freezing was initially used as an intervention for iatrogenic ovarian insufficiency. Nowadays, it is not considered an experimental procedure, and it is increasingly popular among healthy women who wish to maintain their reproductive potential (fertility preservation). This review summarises the evidence on egg freezing technology, reproductive outcomes and long-term effects, as well as its psychological and socioeconomic implications. Egg freezing technology is advancing, with vitrification being the current method of choice, due to its effectiveness. The reproductive outcomes following egg freezing appear to be promising, though the strong negative association with maternal age has to be taken into consideration. Unfortunately, data on long-term outcomes are missing, raising safety issues. Egg freezing has several socioeconomic implications involving health risks, as well as financial and psychological factors.
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http://dx.doi.org/10.1016/j.maturitas.2019.03.017DOI Listing
July 2019

Testicular versus ejaculated spermatozoa for ICSI in patients without azoospermia: A systematic review.

Reprod Biomed Online 2018 Nov 6;37(5):573-580. Epub 2018 Oct 6.

Unit for Human Reproduction, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki Thessaloniki, Greece. Electronic address:

The use of testicular spermatozoa in men without azoospermia has been proposed as a means to increase the chances of pregnancy following assisted reproductive treatment. The purpose of this systematic review is to assess whether clinical outcomes are better when testicular rather than ejaculated spermatozoa are used for intracytoplasmic sperm injection in patients with abnormal semen parameters without azoospermia. A literature search identified four eligible studies out of 757 initially found. In a prospective study in men with high DNA fragmentation index (DFI) and oligozoospermia, the probability of live birth was significantly higher with testicular compared to ejaculated spermatozoa (risk ratio [RR]: 1.75, 95% confidence interval [CI]: 1.14-2.70). This was not the case in a retrospective study in men with high DFI only (RR: 2.36, 95% CI: 0.98-5.68). Clinical pregnancy rates were similar in a randomized controlled trial in men with asthenozoospermia with or without teratozoospermia (RR: 2.85, 95% CI: 0.76-10.69) and in a retrospective study in men with isolated asthenozoospermia (RR: 1.09, 95% CI: 0.56-2.14). Currently, there is limited, low-quality evidence suggesting that a higher probability of pregnancy might be expected using testicular rather than ejaculated spermatozoa, only in men with high DFI and oligozoospermia.
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http://dx.doi.org/10.1016/j.rbmo.2018.08.017DOI Listing
November 2018

Complex chromosomal aberrations in a fetus originating from oocytes with smooth endoplasmic reticulum (SER) aggregates.

Syst Biol Reprod Med 2018 Aug 2;64(4):283-290. Epub 2018 May 2.

c Unit for Human Reproduction, 1st Department of Obstetrics & Gynecology, Papageorgiou General Hospital, Medical School , Aristotle University of Thessaloniki , Thessaloniki , Greece.

The presence of smooth endoplasmic reticulum aggregates (SERa) in the ooplasm is considered as the most severe oocyte dysmorphism due to its serious and potentially lethal outcomes in offspring. In the present case report, a couple underwent their first intracytoplasmic sperm injection (ICSI) cycle using a gonadotrophin releasing hormone (GnRH) antagonist protocol, followed by fetal ultrasound scanning and amniocentesis. SERa were observed in all oocytes retrieved. A singleton pregnancy was established. The second trimester fetal ultrasound scan revealed a female fetus with overlapping fingers in both hands, and amniocentesis was performed for the detection of chromosomal abnormalities. Comprehensive genetic analysis with the combined use of array-comparative genomic hybridization (CGH), fluoresence in situ hybridization (FISH) and conventional cytogenetics revealed a complex chromosome rearrangement (CCR) involving three break points on two chromosomes, resulting in a reciprocal translocation with a cryptic 2q31 deletion. A week following amniocentesis, there was rupture of amniotic membranes and a stillborn was delivered. This is the first case in the literature to report a CCR with concomitant 2q31 deletion resulting in a well-defined and clinically recognizable contiguous gene syndrome with an abnormal phenotype in a fetus arising from a cohort of oocytes affected by SERa. It is suggested that fertilization and transfer of oocytes with SERa should be avoided, until further research establishes whether there is a causal relationship between the presence of SERa and chromosomal abnormalities in the resulting fetus.

Abbreviations: SER: smooth endoplasmic reticulum; ICSI: intracytoplasmic sperm injection; GnRH: gonadotrophin releasing hormone; CGH: comparative genomic hybridization; FISH: fluoresence in situ hybridization; FSH: follicle stimulating hormone; hCG: human chorionic gonadotrophin; OHSS: ovarian hyperstimulation syndrome; IVF: in vitro fertilization; MII: metaphase II; GV: germinal vesicle; CCR: complex chromosome rearrangement.
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http://dx.doi.org/10.1080/19396368.2018.1466375DOI Listing
August 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.

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

Blastocyst utilization rates after continuous culture in two commercial single-step media: a prospective randomized study with sibling oocytes.

J Assist Reprod Genet 2017 Oct 17;34(10):1377-1383. Epub 2017 Jul 17.

Eugonia Assisted Reproduction Unit, 7 Ventiri Street, 11528, Athens, Greece.

Purpose: The aim of this study is to determine whether blastocyst utilization rates are different after continuous culture in two different commercial single-step media.

Methods: This is a paired randomized controlled trial with sibling oocytes conducted in infertility patients, aged ≤40 years with ≥10 oocytes retrieved assigned to blastocyst culture and transfer. Retrieved oocytes were randomly allocated to continuous culture in either Sage one-step medium (Origio) or Continuous Single Culture (CSC) medium (Irvine Scientific) without medium renewal up to day 5 post oocyte retrieval. Main outcome measure was the proportion of embryos suitable for clinical use (utilization rate).

Results: A total of 502 oocytes from 33 women were randomly allocated to continuous culture in either Sage one-step medium (n = 250) or CSC medium (n = 252). Fertilization was performed by either in vitro fertilization or intracytoplasmic sperm injection, and embryo transfers were performed on day 5. Two patients had all blastocysts frozen due to the occurrence of severe ovarian hyperstimulation syndrome. Fertilization and cleavage rates, as well as embryo quality on day 3, were similar in the two media. Blastocyst utilization rates (%, 95% CI) [55.4% (46.4-64.1) vs 54.7% (44.9-64.6), p = 0.717], blastocyst formation rates [53.6% (44.6-62.5) vs 51.9 (42.2-61.6), p = 0.755], and proportion of good quality blastocysts [36.8% (28.1-45.4) vs 36.1% (27.2-45.0), p = 0.850] were similar in Sage one-step and CSC media, respectively.

Conclusions: Continuous culture of embryos in Sage one-step and CSC media is associated with similar blastocyst development and utilization rates. Both single-step media appear to provide adequate support during in vitro preimplantation embryo development. Whether these observations are also valid for other continuous single medium protocols remains to be determined.

Clinical Trial Registration Number: NCT02302638.
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http://dx.doi.org/10.1007/s10815-017-0997-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633582PMC
October 2017

Blastocyst Development in a Single Medium Compared to Sequential Media: A Prospective Study With Sibling Oocytes.

Reprod Sci 2017 09 17;24(9):1312-1318. Epub 2017 Jan 17.

1 Eugonia Assisted Reproduction Unit, Athens, Greece.

The aim of the present study was to compare blastocyst formation rates after embryo culture in a single medium (Global) as compared to sequential media (ISM1/BlastAssist). In this prospective trial with sibling oocytes, 542 metaphase II (ΜΙΙ) oocytes from 31 women were randomly and equally divided to be fertilized and cultured to the blastocyst stage in either sequential media (ISM1/BlastAssist; n = 271 MII oocytes) or a single medium (Global; n = 271 MII oocytes). In both groups, embryos were cultured in an interrupted fashion with media changes on day 3. Embryo transfer was performed on day 5. Blastocyst formation rates on day 5 (61.7% ± 19.9% vs 37.0% ± 25.5%, P < .001) were significantly higher following culture in Global as compared to ISM1/BlastAssist, respectively. Fertilization rates, cleavage rates, and percentage of good quality embryos on day 3 were similar between Global and ISM1/BlastAssist, respectively. The percentages of good quality blastocysts (63.0% ± 24.8% vs 32.1% ± 37.2%, P < .001), blastocysts selected for transfer (27.8% ± 19.2% vs 11.1% ± 14.4%, P = .005), and utilization rates (62.5% ± 24.8% vs 39.0% ± 25.2%, P < .001) were significantly higher in Global as compared to ISM1/BlastAssist, respectively. In conclusion, culture in Global was associated with higher blastocyst formation rates compared to ISM1/BlastAssist, suggesting that the single medium may provide better support to the developing embryo.
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http://dx.doi.org/10.1177/1933719116687653DOI Listing
September 2017

Basal serum progesterone and history of elevated progesterone on the day of hCG administration are significant predictors of late follicular progesterone elevation in GnRH antagonist IVF cycles.

Hum Reprod 2016 08 14;31(8):1859-65. Epub 2016 Jun 14.

Eugovia ART Unit, Athens, Greece.

Study Question: Are there any baseline predictors of progesterone elevation (PE) on the day of human chorionic gonadotrophin (hCG) which are not associated with the intensity of ovarian stimulation in women undergoing in vitro fertilization (IVF) using follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) antagonists?

Summary Answer: Basal (Day 2 of the menstrual cycle) serum progesterone concentration and history of PE are baseline variables that can predict the occurrence of PE on the day of hCG independently of the intensity of ovarian stimulation.

What Is Known Already: PE on the day of hCG is associated with the magnitude of the ovarian response to stimulation. For this reason, it has been hypothesized that milder ovarian stimulation might reduce the probability of PE. However, given the fact that the number of oocytes retrieved is associated with the probability of live birth, such a strategy should be considered only in patients that are at high risk of PE on the day of hCG.

Study Design, Size, Duration: This is a retrospective analysis of a cohort of fresh IVF/ICSI cycles (n = 1702) performed in a single IVF centre during the period 2001-2015.

Participants/materials, Setting, Methods: Patients in whom ovarian stimulation was performed with FSH and GnRH antagonists and with basal FSH <14.0 mIU/ml, progesterone (P) ≤1.6 ng/ml and estradiol (E2) ≤80 pg/ml on the same day (prior to the initiation of stimulation) were considered eligible. PE was defined as serum progesterone concentration >1.5 ng/ml. Pre-stimulation characteristics of patients and basal hormonal profile were assessed for their ability to predict the occurrence of PE after ovarian stimulation through generalized estimating equation univariable and multivariable regression analyses, controlling for the effect of ovarian stimulation. Furthermore, a secondary analysis in a subset of patients with multiple IVF cycles explored whether the occurrence of PE in one of the previous cycles included in this study is associated with a significantly higher occurrence of PE elevation in subsequent cycles.

Main Results And The Role Of Chance: Univariable regression analyses showed that female age (OR: 0.97; 95% CI: 0.94-0.99), basal FSH (OR: 0.85; 95% CI: 0.79-0.92) and basal P (OR: 4.20; 95% CI: 2.47-7.12) were baseline variables that could significantly predict PE on the day of hCG. When these variables were entered in the same model as covariates, only basal FSH (OR: 0.86; 95% CI: 0.80-0.94) and basal P (OR: 3.83; 95% CI: 2.24-6.56) could still predict the occurrence of PE. Basal P (OR: 6.30; 95% CI: 3.35-11.82) was the only variable that could significantly predict the occurrence of PE on the day of hCG after adjusting for the intensity of ovarian stimulation. The secondary analysis revealed that history of PE on the day of hCG in a previous cycle was also strongly associated with an increased risk of PE in a subsequent cycle.

Limitations, Reasons For Caution: This is a retrospective analysis and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded.

Wider Implications Of The Findings: The findings of this study might help clinicians identify patients at high risk for late follicular PE and alter the management of their cycle.

Study Funding/competing Interests: None.

Trial Registration Number: Not applicable.
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http://dx.doi.org/10.1093/humrep/dew141DOI Listing
August 2016

Thyroid function and IVF outcome: when to investigate and when to intervene?

Curr Opin Obstet Gynecol 2016 06;28(3):191-7

aUnit of Reproductive Endocrinology bUnit of Human Reproduction, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece.

Purpose Of Review: To summarize the evidence regarding the need to assess thyroid function in women undergoing ovarian stimulation as well as the need to intervene when thyroid function is suboptimal.

Recent Findings: There is now evidence that ovarian stimulation can influence thyroid function not only via hyperestrogenism but also directly, since thyroid-related receptors are present in human granulosa cells and in the endometrium. Prospective and retrospective observational studies, as well as a few clinical trials, have been conducted in an effort to clarify the association between ovarian stimulation and thyroid function with controversial results.

Summary: The need of thyroid function screening with thyroid stimulating hormone (TSH) in infertile women attempting pregnancy is recognized by many international societies. Since TSH is a simple, cheap screening tool and levothyroxine (LT4) supplementation is an easy to apply, cheap and well tolerated intervention, universal thyroid screening in women undergoing IVF represents a reasonable policy. In case of subclinical hypothyroidism, when TSH exceeds the threshold of 4.0 or 4.5 μIU/ml before IVF, LT4 replacement should be administered, while the same intervention might also be justified for women with TSH concentration more than 2.5 μIU/ml before IVF.
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http://dx.doi.org/10.1097/GCO.0000000000000263DOI Listing
June 2016

Propofol versus thiopental sodium as anaesthetic agents for oocyte retrieval: a randomized controlled trial.

Reprod Biomed Online 2015 Dec 4;31(6):752-9. Epub 2015 Sep 4.

Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Greece.

Clinical outcomes of IVF cycles using propofol or thiopental sodium as anaesthetic agents for oocyte retrieval were compared. The primary outcome measure was fertilization rate per patient. One hundred and eighty patients undergoing ovarian stimulation with gonadotrophins and gonadotrophin-releasing hormone antagonists for IVF were randomized to receive either propofol (n = 90) or thiopental sodium (n = 90). No significant differences in baseline characteristics were present between the two groups. Overall fertilization rates were similar between propofol and thiopental sodium groups, respectively: median (IQR): 54.8 (29.2) versus 54.6 (29.7); fertilization rates for intracytoplasmic sperm injection only: median (IQR): 70 (50) versus 75 (50), respectively. For secondary outcome measures, time under anaesthesia was significantly increased in the thiopental sodium group: median (IQR): 12(5) versus 10 (4.5) min, P = 0.019 compared with the propofol group. Number of cumulus oocyte complexes retrieved [median (IQR): 7.1 (6.3) versus 6.5 (5.6)] did not differ significantly between the two groups. A non-significant difference in live birth rates per randomized patient of +4.4% (95% CI: -5.7 to +14.6) in favour of propofol was observed. Use of propofol compared with thiopental sodium for general anaesthesia during oocyte retrieval results in similar fertilization rates and IVF outcomes.
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http://dx.doi.org/10.1016/j.rbmo.2015.08.013DOI Listing
December 2015

Reply: Modified natural cycles for poor responders: addressing misconceptions and fallacies.

Hum Reprod 2016 Jan 27;31(1):222-3. Epub 2015 Oct 27.

Department of Women's and Children's Health, St George Hospital, School of Women's and Children's Health, University of New South Wales, Kogarah, NSW 2217, Australia.

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http://dx.doi.org/10.1093/humrep/dev262DOI Listing
January 2016

Thyroid function and autoimmunity during ovarian stimulation for intracytoplasmic sperm injection.

Reprod Fertil Dev 2017 Mar;29(3):603-608

Unit of Reproductive Endocrinology and Unit of Human Reproduction, First Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki, Greece.

The aim of the present study was to assess changes in thyroid function and thyroid autoimmunity (TAI) throughout ovarian stimulation (OS) for intracytoplasmic sperm injection (ICSI) and the association of these changes with ICSI outcome. A flexible gonadotrophin-releasing hormone (GnRH) antagonist protocol was used in 42 women and their thyroid function and TAI were assessed at baseline and five times during OS (Days 3 and 5 of the menstrual cycle, the day of hCG administration, the day of ovum pick-up and the day of the pregnancy test). The primary outcome measure was the change in thyroid function throughout OS. No overall change was recorded in thyrotropin-stimulating hormone (TSH) concentrations throughout OS (P=0.066). In women who became pregnant (n=8), an increase in TSH concentrations was noted on the day of the pregnancy test compared with Day 3 of the menstrual cycle (3.410±1.200 vs 2.014±0.950μIU mL, respectively; P=0.001; mean ± s.d.). TAI was present in 11 of 42 women. Biochemical pregnancy was negatively correlated with changes in TSH (r=-0.7, P=0.004). No such association was noted regarding the live birth rate. The present study provides evidence that TSH concentrations could increase during OS, especially in women who become pregnant.
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http://dx.doi.org/10.1071/RD15172DOI Listing
March 2017

Is the time interval between HCG administration and oocyte retrieval associated with oocyte retrieval rate?

Reprod Biomed Online 2015 Nov 13;31(5):625-32. Epub 2015 Aug 13.

Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

The aim of this study was to evaluate whether prolongation of the time interval between HCG administration and oocyte retrieval, from 36 h to 38 h, affects oocyte retrieval rate in women undergoing ovarian stimulation with gonadotrophins and GnRH antagonists for IVF. One hundred and fifty-six normo-ovulatory women were randomized to have oocyte retrieval performed 36 h (n = 78) or 38 h (n = 78) following HCG administration. Oocyte retrieval rate was defined as number of cumulus-oocyte-complex (COC) retrieved/follicle ≥ 11 mm present on day of HCG administration. No significant differences were observed between the groups regarding baseline characteristics. Moreover, no significant difference was observed between the groups regarding oocyte retrieval rate (difference: + 1.2%, 95% CI for difference between medians: -4.5 to +12.1). The median (95% CI for the median) was not significantly different between the groups regarding number of cumulus-oocyte-complexes (COCs) retrieved: 5.5 (5.0-7.0) versus 6.0 (5.0-6.2), respectively, and fertilization rates: 57.7% (50.0-66.7) versus 50.0% (44.8-65.5), respectively. Live birth rates were similar between the groups (20.5% versus 16.7%, RD: + 3.8%, 95% CI: -8.5 to +16.1, respectively). Prolongation of time interval between HCG administration and oocyte retrieval from 36 h to 38 h does not affect oocyte retrieval rate.
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http://dx.doi.org/10.1016/j.rbmo.2015.08.005DOI Listing
November 2015

Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders.

Hum Reprod 2015 Oct 25;30(10):2321-30. Epub 2015 Aug 25.

Unit for Human Reproduction, 1st Department of Obstetrics & Gynaecology, Papageorgiou General Hospital, Medical School, Aristotle University of Thessaloniki, Ring Road, Nea Efkarpia, Thessaloniki 56429, Greece

Study Question: Do live birth rates differ between modified natural cycles (MNCs) and cycles using high-dose follicle stimulating hormone (HDFSH) with gonadotrophin-releasing hormone (GnRH) antagonist in poor responder patients?

Summary Answer: Live birth rates are significantly higher in MNC compared with HDFSH GnRH antagonist cycles in poor responder patients.

What Is Known Already: Previous data on the efficiency of MNC in poor responders are very limited and suggest that MNC in vitro fertilization (IVF) does not offer a realistic solution for parenthood in these patients, since live birth rates are disappointingly low. To date, no studies exist comparing MNC with HDFSH stimulation protocols in poor responders.

Study Design, Size, Duration: The present retrospective study included 161 MNCs (106 women in the MNC group) and 164 HDFSH antagonist cycles (136 women in the HDFSH group) performed between January 2008 and December 2013 at Eugonia Assisted Reproduction Unit. The patients included in the study had to fulfill the Bologna criteria for the definition of poor ovarian response.

Participants/materials, Setting, Methods: Irrespective of their age, poor responder patients should have a diminished ovarian reserve as shown by low antral follicle count (≤5) and increased basal FSH (>12 IU/l), and one or more previous failed IVF cycles in which ≤3 oocytes were retrieved using a high gonadotrophin dose. Analysis was performed by adjusting for the non-independence of the data.

Main Results And The Role Of Chance: The probability of live birth was significantly higher in the MNC when compared with the HDFSH group (OR: 4.01, 95% CI: 1.14-14.09), after adjusting for basal FSH, female age and cause of infertility, variables which were shown to be associated with the probability of live birth in univariable analysis. MNCs were characterized by significantly lower total gonadotrophin dose (490.0 ± 35.2 IU versus 2826.1 ± 93.4 IU, P < 0.001), lower estradiol concentrations (237.5 ± 12.3 pg/ml versus 487.3 ± 29.8 pg/ml, P < 0.001), fewer follicles present on the day of hCG (1.9 ± 0.1 versus 3.2 ± 0.2, P < 0.001), fewer oocytes retrieved (1.1 ± 0.01 versus 2.4 ± 0.1, P < 0.001), fewer oocytes fertilized (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer embryos transferred (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer good-quality embryos available (0.5 ± 0.1 versus 0.8 ± 0.1, P < 0.001) and fewer good-quality embryos transferred (0.5 ± 0.05 versus 0.8 ± 0.1, P < 0.001) compared with the HDFSH group. However, the proportion of cycles with at least one good-quality embryo transferred per started cycle was similar between the two groups compared (62.5, 95% CI: 52.7-72.3 versus 62.7, 95% CI: 53.0-72.5, respectively).

Limitations, Reasons For Caution: This is a retrospective comparison between MNC and HDFSH GnRH antagonist protocols in a large group of poor responder patients according to the Bologna criteria. Although the two groups compared were not imbalanced for all basic characteristics and multivariate analysis were performed to adjust for all known confounders, it cannot be excluded that non-apparent sources of bias might still be present. Future randomized controlled trials are necessary to verify the present findings.

Wider Implications Of The Findings: Both MNC and HDFSH antagonist protocols offer very low chances of live birth in poor responder patients who fulfill the Bologna criteria. However, MNC-IVF is a more patient-friendly approach, with a higher probability of live birth compared with the HDFSH antagonist protocol. In this respect, the current data might be of help in counseling such patients, who do not wish to undergo oocyte donation, prior to abandoning treatment altogether and/or proceeding to adoption.

Study Funding/competing Interests: No funding was obtained. C.A.V. reports personal fees and non-financial support from Merck, Sharp and Dome, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from IPSEN Hellas S.A. outside the submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp & Dohme, personal fees from IBSA, personal fees from Merck Sharp & Dohme and personal fees from Ovascience outside the submitted work .
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http://dx.doi.org/10.1093/humrep/dev198DOI Listing
October 2015

Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved.

J Assist Reprod Genet 2015 May 11;32(5):691-7. Epub 2015 Mar 11.

Eugonia Assisted Reproduction Unit, 7 Ventiri Street, 11528, Athens, Greece,

Purpose: To compare reproductive outcomes following conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in poor responders fulfilling the Bologna criteria, with a single oocyte retrieved.

Methods: The present retrospective study included 243 Bologna poor responders with a single oocyte retrieved, who were categorized into three groups, depending on the fertilization method and semen quality (IVF non-male factor-IVF/NMF n = 101; ICSI non-male factor ICSI/NMF n = 50; ICSI male factor-ICSI/MF n = 92).

Results: In IVF/NMF, ICSI/NMF and ICSI/MF similar fertilization rates [65.3, 66, 58.7%, respectively], proportions of embryo formation [63.4, 60, 53.3%, respectively], proportions of good quality embryos [54.7, 56.7, 57.1%, respectively], implantation rates [8.9, 10, 8.2% respectively] and live birth rates per oocyte retrieval [5.0, 4.0, 3.3%, respectively] were observed. Degeneration rate of oocytes due to mechanical damage was significantly higher after ICSI in the ICSI/NMF and ICSI/MF groups (8 and 6.5%, respectively) compared to IVF/NMF (0%) (p = 0.02).

Conclusions: Conventional IVF and ICSI are associated with similar reproductive outcomes in poor responder patients with a single oocyte retrieved. Therefore, the choice of fertilization method should be based primarily on semen quality, in combination with the patient's previous history. A randomized controlled trial should be performed to confirm this study's findings that conventional IVF and ICSI have similar reproductive outcomes in poor responders.
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http://dx.doi.org/10.1007/s10815-015-0459-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429441PMC
May 2015

Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles.

Hum Reprod 2015 Mar 12;30(3):684-91. Epub 2015 Jan 12.

Eugonia - IVF Unit, Athens, Greece.

Study Question: What is the proper way of assessing the effect of progesterone elevation (PE) on the day of hCG on live birth in women undergoing fresh embryo transfer after in vitro fertilization (IVF) using GnRH analogues and gonadotrophins?

Summary Answer: This study indicates that a multivariable approach, where the effect of the most important confounders is controlled for, can lead to markedly different results regarding the association between PE on the day of hCG and live birth rates after IVF when compared with the bivariate analysis that has been typically used in the relevant literature up to date.

What Is Known Already: PE on the day of hCG is associated with decreased pregnancy rates in fresh IVF cycles. Evidence for this comes from observational studies that mostly failed to control for potential confounders.

Study Design, Size, Duration: This is a retrospective analysis of a cohort of fresh IVF/intracytoplasmic sperm injection cycles (n = 3296) performed in a single IVF centre during the period 2001-2013.

Participants/materials, Setting, Methods: Patients in whom ovarian stimulation was performed with gonadotrophins and GnRH analogues. Natural cycles and cycles where stimulation involved the administration of clomiphene were excluded. In order to reflect routine clinical practice, no other exclusion criteria were imposed on this dataset. The primary outcome measure for this study was live birth defined as the delivery of a live infant after 24 weeks of gestation. We compared the association between PE on the day of hCG (defined as P > 1.5 ng/ml) and live birth rates calculated by simple bivariate analyses with that derived from multivariable logistic regression. The multivariable analysis controlled for female age, number of oocytes retrieved, number of embryos transferred, developmental stage of embryos at transfer (cleavage versus blastocyst), whether at least one good-quality embryo was transferred, the woman's body mass index, the total dose of FSH administered during ovarian stimulation and the type of GnRH analogues used (agonists versus antagonists) during ovarian stimulation. In addition, an interaction analysis was performed in order to assess whether the ovarian response (<6, 6-18, >18 oocytes) has a moderating effect on the association of PE on the day of hCG with live birth rates after IVF.

Main Results And The Role Of Chance: Live birth rates were not significantly different between cycles with and those without PE when a bivariate analysis was performed [odds ratio (OR): 0.78, 95% confidence interval (CI): 0.56-1.09]. However, when a multivariable analysis was performed, controlling for the effect of the aforementioned confounders, live birth rates (OR: 0.68, 95% CI: 0.48-0.97) were significantly decreased in the group with PE on the day of hCG. The number of oocytes retrieved was the most potent confounder, causing a 29.4% reduction in the OR for live birth between the two groups compared. Furthermore, a moderating effect of ovarian response on the association between PE and live birth rates was not supported in the present analysis since no interaction was detected between PE and the type of ovarian response (<6, 6-18, >18 oocytes).

Limitations, Reasons For Caution: This is a retrospective analysis of data collected during a 12-year period, and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded.

Wider Implications Of The Findings: This analysis highlights the need for a multivariable approach when researchers or clinicians aim to evaluate the impact of PE on pregnancy rates in their own clinical setting. Failure to do so might explain why many past studies have failed to identify the detrimental effect of PE in fresh IVF cycles.

Study Funding/competing Interests: None.
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http://dx.doi.org/10.1093/humrep/deu362DOI Listing
March 2015

Is assessment of anti-Müllerian hormone and/or antral follicle count useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists? A prospective observational study.

Gynecol Endocrinol 2014 Nov 3;30(11):817-21. Epub 2014 Jul 3.

Unit for Human Reproduction, 1st Dept. of OB/Gyn, Medical School, Aristotle University of Thessaloniki , Greece .

The purpose of this prospective observational study was to evaluate whether the assessment of AMH and AFC is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH (rec-FSH) and GnRH antagonists. A base model including age and basal FSH as independent predictors of COCs could explain 15% of the variance observed in the number of COCs retrieved (p = 0.002). The addition of AFC did not increase significantly the predictive ability of the above model, whereas the addition of AMH increased the performance of the base model by 13% (p < 0.001). Logistic regression analysis showed that only when AMH was added to the base model, including age and FSH, its predictive capacity for high ovarian response was statistically significant (F-test: p = 0.001; c-statistic: 0.80, 95% CI: 0.70-0.88), but this was not the case for poor ovarian response. In conclusion, the addition of AMH, but not of AFC, to a model including female age and basal FSH, is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists.
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http://dx.doi.org/10.3109/09513590.2014.938624DOI Listing
November 2014

Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis.

Reprod Biol Endocrinol 2014 Feb 20;12:17. Epub 2014 Feb 20.

Faculty of Economics, Université Catholique de Louvain (UCL Mons), 7000 Mons, Belgium.

Background: The potential benefit of adding recombinant human luteinizing hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) during ovarian stimulation is a subject of debate, although there is evidence that it may benefit certain subpopulations, e.g. poor responders.

Methods: A systematic review and a meta-analysis were performed. Three databases (MEDLINE, Embase and CENTRAL) were searched (from 1990 to 2011). Prospective, parallel-, comparative-group randomized controlled trials (RCTs) in women aged 18-45 years undergoing in vitro fertilization, intracytoplasmic sperm injection or both, treated with gonadotrophin-releasing hormone analogues and r-hFSH plus r-hLH or r-hFSH alone were included. The co-primary endpoints were number of oocytes retrieved and clinical pregnancy rate. Analyses were conducted for the overall population and for prospectively identified patient subgroups, including patients with poor ovarian response (POR).

Results: In total, 40 RCTs (6443 patients) were included in the analysis. Data on the number of oocytes retrieved were reported in 41 studies and imputed in two studies. Therefore, data were available from 43 studies (r-hFSH plus r-hLH, n=3113; r-hFSH, n=3228) in the intention-to-treat (ITT) population (all randomly allocated patients, including imputed data). Overall, no significant difference in the number of oocytes retrieved was found between the r-hFSH plus r-hLH and r-hFSH groups (weighted mean difference -0.03; 95% confidence interval [CI] -0.41 to 0.34). However, in poor responders, significantly more oocytes were retrieved with r-hFSH plus r-hLH versus r-hFSH alone (n=1077; weighted mean difference +0.75 oocytes; 95% CI 0.14-1.36). Significantly higher clinical pregnancy rates were observed with r-hFSH plus r-hLH versus r-hFSH alone in the overall population analysed in this review (risk ratio [RR] 1.09; 95% CI 1.01-1.18) and in poor responders (n=1179; RR 1.30; 95% CI 1.01-1.67; ITT population); the observed difference was more pronounced in poor responders.

Conclusions: These data suggest that there is a relative increase in the clinical pregnancy rates of 9% in the overall population and 30% in poor responders. In conclusion, this meta-analysis suggests that the addition of r-hLH to r-hFSH may be beneficial for women with POR.
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http://dx.doi.org/10.1186/1477-7827-12-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015269PMC
February 2014

Association of TSH concentrations and thyroid autoimmunity with IVF outcome in women with TSH concentrations within normal adult range.

Gynecol Obstet Invest 2014 14;77(2):84-8. Epub 2013 Dec 14.

Unit of Reproductive Endocrinology and Unit of Human Reproduction, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background/aims: This study aimed to evaluate the association of thyroid-stimulating hormone (TSH) concentrations and presence of thyroid autoimmunity (TAI) with the live birth rate in euthyroid women undergoing in vitro fertilization (IVF).

Methods: This study of retrospective design included 158 euthyroid women (TSH 0.5-4.5 µIU/ml) who underwent IVF from January 2006 to December 2010. Thyroid parameters were measured on day 3 of the previous nontreatment cycle. Women were subgrouped and analyzed according to their TSH concentrations (low: 0.5-2.5 vs. high: 2.6-4.5 µIU/ml) and TAI (present vs. absent).

Results: No difference in the live birth rate was found between the TSH (low: 34.2% vs. high: 36.8%, p = 0.763) or TAI (present: 26.7% vs. absent: 34.3%, p = 0.568) subgroups.

Conclusion: This study found no evidence that increased TSH concentrations or the presence of TAI determined before IVF affect the live birth rate in euthyroid women. A better insight into the role of thyroid function during application of IVF is needed.
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http://dx.doi.org/10.1159/000357193DOI Listing
December 2014

Reply of the authors.

Fertil Steril 2014 Jan 26;101(1):e5-6. Epub 2013 Nov 26.

Merck Sharp & Dohme Corp., Whitehouse Station, New Jersey.

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http://dx.doi.org/10.1016/j.fertnstert.2013.10.037DOI Listing
January 2014

Association of the CYP2B6 c.516G>T polymorphism with high blood propofol concentrations in women from northern Greece.

Drug Metab Pharmacokinet 2014 22;29(2):215-8. Epub 2013 Oct 22.

Department of Forensic Medicine and Toxicology, Medical School, Aristotle University of Thessaloniki.

Cytochrome P450 2B6 (CYP2B6) is responsible for the initial biotransformation of profol, an extensively metabolized intravenous anesthetic. In this study we examined the effect of the apparently functional CYP2B6 c.516G>T polymorphism on the distribution of propofol concentrations, quantified by GC/MS analysis following a single bolus dose, in the blood of 44 Greek women undergoing oocyte retrieval. Univariate analysis using age, height, weight and smoking status as covariates, as well as the Mann-Whitney non-parametric test, revealed a strong trend of association of the T allele with high propofol concentrations determined in whole blood, shortly after a single bolus dose. Propofol concentrations which were higher than one standard deviation of the mean were almost invariably associated with carriage of the T allele.
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http://dx.doi.org/10.2133/dmpk.dmpk-13-nt-092DOI Listing
December 2014