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Generating translatable evidence to improve patient care has proved challenging in reproductive medicine, with many “add-on” treatments in routine assisted conception clinical practice, which have not been reliably tested. This has consequences for patient care; specifically, IVF pregnancy rates have not improved. A change of culture is required in our profession, from indiscriminately applying the latest “add-on”, to whole-scale participation in generating reliable translatable evidence.

Introduction. Serum proteins PAPP-A (pregnancy-associated plasma protein-A) and β-hCG (the в-subunit of human chorionic gonadotropin) levels are components of the 1st trimester combined screening aimed to detect fetal aneuploidies. In contrast to singleton pregnancies, where the values are well established, this is not the case in twins. Aim : a comparative analysis of serum proteins PAPP-A and β-hCG levels, as well as parameters PAPP-A MoM and β-hCG MoM in the first trimester during pregnancy with dichorionic diamniotic twins that occurred spontaneously or as a result of in vitro fertilization (IVF). Materials and methods . The study group included multiple pregnancies as a result of IVF procedure (n = 100) and spontaneous multiple pregnancies (n = 121) considered as controls. The levels of PAPP-A, β-hCG, PAPP-A MoM and β-hCG MoM were compared using nonparametric Mann-Whitney U test. Results. The PAPP-A MoM level resulted higher in the group of IVF twins (p = 0,007) compared to spontaneous twins: 1.28 [0.97; 1.89] vs. 1.12 [0.87; 1.40] (median [interquartile range]). There were no statistically significant differences in в-hCG levels between the groups of IVF twins and spontaneous twins. Conclusion. The results justify the need for further study of PAPP-A and β-hCG to establish their association with adverse outcomes in both groups of multiple pregnancies.

Study question Do cytogenetic results from products of conception from miscarriages differ from patients conceiving by natural conception versus IVF? Summary answer: Cytogenetic results were similar, with no statistical difference from miscarriages following natural conception and assisted conception. What is known already Cytogenetic sampling of products of conception (POC) following recurrent miscarriages (RM) are recommended to rule out parental chromosomal rearrangements. The RCOG recommends cytogenetic testing in cases of recurrent miscarriages (3 consecutive miscarriages). However some units routinely request cytogenetic analysis following a single miscarriage following an IVF pregnancy. There is no evidence to support the routine sampling of POCs following assisted conception. Study design, size, duration: Retrospective cohort study of 117 cytogenetic samples, followed up by the outcome of parental karyotyping if applicable. Patients were categorised based on mode of conception into natural conception (NC) with recurrent miscarriages (≥3) or one miscarriage following IVF. Data collected between 2018–2020. Primary Outcome measure: Presence and type of cytogenetic abnormality; individual parental targeted G-band karyotyping result. Participants/materials, setting, methods: A total of 117 cytogenetic results were reviewed, of which 35 were unsuitable for analysis due to contamination (Total n = 79: NC = 60, IVF = 19). Main results and the role of chance: Cytogenetic analysis showed abnormal results in 59% of miscarriages following natural conception and 53% of miscarriages from IVF pregnancy (p = 0.46). Abnormal cytogenetic results were mainly sporadic. Trisomy 16 was the commonest abnormality in both groups. Others included Trisomy 15, 22, 21, 8, 13, 5, 9, 10, 14, 18, single X (Turner’s), all occurring in the same frequency in both groups. As expected 35 out of 45 abnormal cytogenetic results occurred with a maternal age greater than 35 years. One couple from the NC group were referred to a geneticist for a Trisomy 9 imbalance. All other parental karyotyping results were normal. Limitations, reasons for caution This study contains a small sample size, and would benefit from further data collection to account for a percentage of samples being inadequate for analysis. Wider implications of the findings: Cytogenetic results were similar from miscarriages following natural conception and assisted conception. IVF does not increase the risk of miscarriage from abnormal embryonic karyotype. Routine cytogenetic testing following one miscarriage in patients undergoing IVF is not cost effective. Trial registration number Not applicable

Research question What is the influence of the Caesarean section–pregnancy interval (CSPI) on the risk of uterine rupture, and what are the repercussions on IVF pregnancy rates of prolonging it? Study design Systematic searches were performed using PubMed MEDLINE to identify studies published up until July 2017 for articles with the following keywords: ‘interdelivery interval’ and ‘uterine rupture’; ‘interpregnancy interval’ and ‘uterine rupture’; ‘interpregnancy interval’ and ‘cesarean section’; and ‘uterine rupture’ and ‘cesarean section’. The search identified 1609 articles, of which six were included (involving 56,419 women). Four reported significantly higher uterine rupture rates in cases of a short CSPI. Results From the analysis, the uterine rupture rate can be modelled by a formula corresponding to a hyperbolic curve. There is no clear cut-off in uterine rupture in relation to CSPI. The curve showed a sharp decrease in uterine rupture until the 10th month of CSPI (uterine rupture rate 0.7%), then a moderate and steady decrease until the 40th month (uterine rupture rate 0.4%) and afterwards a very mild decrease. From the data it is possible to calculate, according to the age of the woman, the expected reduction in IVF rates and uterine rupture as CSPI increases. Conclusion The risk of uterine rupture in relation to CSPI can be represented by means of a hyperbolic curve. After a 10-month CSPI, the expected uterine rupture rate is close to 0.7%. The impact of prolonging or reducing this interval on IVF pregnancy rates can be easily obtained from the table included in the article. This should be helpful in the decision-making process for both patients and physicians.

In November 2018 a Chinese scientist claimed to have used CRISPR/Cas 9 technology to genetically modify two human embryos that were then gestated in one adult woman through an IVF pregnancy and brought to term. The twin girls are allegedly the first babies born with their prenatal genomes edited. Using both English language and Chinese supporting documents, this paper discusses the background of this human experiment, the social context of Chinese science, and the alleged ethical transgressions of its principal scientist.

The redacted classification of placental lesions identifies in the group of fetal-stromal vascular lesions a subgroup called villous capillary lesions. The causes of villous capillary lesions appear to involve excessive angiogenesis. These conditions include chorangiosis, chorangiomatosis, chorangioma and a rare variant of the latter called multiple chorangioma syndrome where multiple chorangiomas, ranging from very small early precursor lesions to typical macroscopic chorangioma, occupy up to 80% of the total placental parenchyma. We present the first case of multiple chorangioma syndrome in an oncologic patient who obtained the pregnancy by egg donation, comparing the clinical case with ones available in literature. Fifteen cases have been previously published in literature but only 11 were eligible for the present review. We compared clinical characteristics and fetal outcomes with our clinical case, to highlight similarities and differences useful for a better understanding of this rare and partially unknown disease. Multiple chorangioma syndrome is a rare villous capillary lesion associated with poor fetal condition. All cases analyzed have been conceived naturally and our case is the first described in an IVF pregnancy. We believe that in our case the advanced maternal age, the method of conception and the previous chemo-therapeutic treatments might have played an important role in determining the manifestation of this rare placental condition. However, there is not appropriate literature supporting our consideration and, for future studies, it could be reasonable investigate the incidence of this condition, or even the incidence of all cluster of villous capillary lesions, in oncologic and IVF patients.

International audience; Background: In a previous study, we showed that the obstetric complication rate after in vitro fertilization (IVF) pregnancy was 40%. The main objective of our study was to determine maternal prognosis factors that influence the IVF pregnancy outcome.Methods: We conducted an observational retrospective monocentric study between January 2014 and January 2018. Pregnancy over 22 gestational weeks (GW) obtained after IVF in our infertility clinic was included. Maternal characteristics and pregnancy outcome were collected.Results: Data from 498 IVF pregnancies were analyzed. The most significant maternal prognosis factors for obstetric complications were maternal age above 40 years (OR 3,0 [95% IC 1,30-7,09], P = 0,010), twin pregnancies (3.8 [95% IC 1.49-9.99], P = .005), daily maternal smoking above 10 cigarettes (7.1 [95% IC 1.22-41.74], P = .029), maternal obesity (2.2 [95% IC 1.19-4.07], P = .012), endometriosis stages III and IV (6.4 [95% IC 1.52-27.04], P = .011), and history of ovarian hyperstimulation syndrome (OHSS) in early pregnancy (5.7 [95% IC 1.29-24.74], P = .021). Risk increase was independent of pregnancy type (singleton or twin) and allowed the elaboration of 2 nomograms.Conclusions: Our study showed a link between some maternal factors and increase in obstetric complications after IVF. Screening of these factors during preconceptional visit is essential to identify at high-risk pregnancies and adapt their monitoring.

With the first successful report of an IVF pregnancy achieved via donor oocytes in 1984, the applications of assisted reproductive technology (ART) were further expanded to include women unable to conceive with their own oocytes. Today, oocyte donation makes up an increasingly large percentage of all ART cycles worldwide. Oocyte donation presents several unique challenges to clinicians as two separate interests, those of the donor and those of the recipient, must be represented. These challenges include successful preparation of the endometrium in donor oocyte recipients, the synchronization of donor/recipient cycles, and the optimization of ovarian stimulation while maximizing donor safety. Facing these challenges has not only allowed for the creation of successful donor egg programs but has also provided insights into many aspects of ART. Much of what we know about the window of implantation, frozen ET procedures, triggering of oocyte maturation, and fertility preservation has been learned through experience and investigations with donor egg cycles. Not only has oocyte donation, through its optimization and wide use, provided new treatment opportunities for patients, it has also become a critical scientific tool to study many aspects of menstrual cycle dynamics and implantation. Concomitantly, with its increased efficiency, it has also raised several clinical and ethical challenges.

Chromosomal polymorphisms are associated with infertility, but their effects on assisted reproductive outcomes are still quite conflicting, especially after IVF treatment. This study evaluated the role of chromosomal polymorphisms of different genders in IVF pregnancy outcomes. Four hundred and twenty-five infertile couples undergoing IVF treatment were divided into three groups: 214 couples with normal chromosomes (group A, control group), 86 couples with female polymorphisms (group B), and 125 couples with male polymorphisms (group C). The pregnancy outcomes after the first and cumulative transfer cycles were analyzed, and the main outcome measures were live birth rate (LBR) after the first transfer cycle and cumulative LBR after a complete IVF cycle. Comparison of pregnancy outcomes after the first transfer cycle within group A, group B, and group C demonstrated a similar LBR as well as other rates of implantation, clinical pregnancy, early miscarriage, and ongoing pregnancy (P > 0.05). However, the analysis of cumulative pregnancy outcomes indicated that compared with group A, group C had a significantly lower LBR per cycle (80.4 vs 68.00%), for a rate ratio of 1.182 (95% CI 1.030 to 1.356, P = 0.01) and a significantly higher cumulative early miscarriage rate (EMR) among clinical pregnancies (7.2 vs 14.7%), for a rate ratio of 0.489 (95% CI 0.248 to 0.963, P = 0.035). Couples with chromosomal polymorphisms in only male partners have poor pregnancy outcomes after IVF treatment manifesting as high cumulative EMR and low LBR after a complete cycle.

Typically, all fetuses of a multiple gestations deliver within a short interval; however, in selected cases, the preterm birth of one fetus may not require delivery of the other fetus (es). An extended time interval between births of siblings at a critical gestational age may improve neonatal survival and reduce morbidity from preterm birth. We report a case of 41year old woman with twin IVF pregnancy, in which the first twin delivered at 22 weeks and the second twin was delivered at 31 weeks with a favourable outcome. Conclusion: With the increasing use of ART and consequent multifetal gestation, premature delivery is the most dreaded complication with the loss of all babies. In recent years the approach to the fate of after coming twins during preterm delivery has changed. Desperate attempts to salvage the second twin by delaying delivery have been reported recently in some cases with favourable outcome for the second twin.

Background In the assisted reproduction, the infertile molecules of spermatozoa from normozoospermic men who underwent the unexplained failure of in vitro fertilization (IVF) due to the lack of sperm binding to the normal zona pellucida, and then achieved pregnancy with the rescue intracytoplasmic sperm injection (R-ICSI) remain unclear. More works are still necessary to explore this male infertile mechanism. Methods Normozoospermicmen with the IVF pregnancy and normozoospermic men with the R-ICSI pregnancy after the conventional IVF failure were collected. iTRAQ-based proteomic approach were performed to reveal the new infertile causes between the IVF pregnancy men and the R-ICSI pregnancy men. To validate the confidence of proteome data, the individual samples were analyzed by western blot and immunofluorescence. Further, the spontaneous acrosome reactions were measured to evaluate the sperm quality. Results Compared with IVF pregnancy group, 56 sperm proteins were differentially expressed in the R-ICSI pregnancy group. Bioinformatic analyses (PANTHER, DAVID, PubMed and STRING) indicated these altered sperm proteins were involved in various molecular functions: reproduction, chromosome organization, and sperm-oocyte interaction. Moreover, the confidence of proteome data was confirmed by western blot and immunofluorescence using the individual samples, which were consistent with our proteomic data. Additionally, an increased rate of the spontaneous acrosome reaction rate was found in the R-ICSI pregnancy group. Conclusions The sealtered sperm proteins and the increased spontaneous acrosome reaction rate might account for this unexplained male infertility in the R-ICSI pregnancy patients. The present proteomic results will throw light on the better understanding of the unexplained infertile mechanisms underlying these normozoospermic man who achieved R-ICSI pregnancy after IVF failure. Electronic supplementary material The online version of this article (10.1186/s12014-018-9203-3) contains supplementary material, which is available to authorized users.

Objective: GLP-1 has been investigated in regulation of reproductive system in animal models. Current observations suggest that it directly regulates kisspeptin and GnRH expression and that ovaries express GLP-1 mRNA. Aim: To evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle modification and resistant to first line reproductive treatments. Design/Participants/Methods: A prospective randomized open-label study was conducted with 28 infertile obese PCOS patients (aged 31,07±4,75 years, BMI 36,7±3,5 kg/m2, mean ± SD). They were assigned to metformin (MET) 1000 mg BID or combined MET 1000 mg BID and low dose liraglutide 1.2 mg QD s.c. (COMBI) for 12 weeks. Ovarian stimulation protocol was started after 4-week medication free period. Results: Patients in MET lost on average 7,0±6,0 kg (P Conclusion: Short-term preconception intervention with low dose liraglutide as an add on to metformin was superior to metformin alone in increasing PR per ET and cumulative PR in infertile obese PCOS, despite comparable weight reduction in both arms. Potential direct crosstalk between GLP-1 and reproductive system needs further exploration. Disclosure A. Janez: None. M. Jensterle: None.

Sclerosing encapsulating peritonitis (SEP) is the total or partial encapsulation of intraabdominal organs by a dense fibrous membrane. Numerous mechanisms may predispose to peritoneal irritation, w...

The aim of this study is to investigate whether the presence of mucous, blood and microorganisms, as detected on catheters used for ET alters the outcome of IVF-ET.

Objective: A Prospective and retrospective analysis of POSEIDON stratification to predict low prognosis patients during assisted reproductive technique (ART) cycles in Indian Population. Design: Bidirectional Study (Prospective as well as Retrospective). Setting: Southend fertility and IVF centre, New Delhi. Patient Selection: All Low prognosis patients according to POSEIDON stratification. Duration of Study: 06 Months. Outcome: Prevalence of Low prognosis patients in Indian Population and Clinical Pregnancy Rate in whom fresh embryo transfer was done. Results: In this bidirectional study we enrolled a total 456 patients who underwent ovarian stimulation for ART at Southend Fertility and IVF Centre from Jan 2017 to Dec 2018. Out of these patients 218 (47%) patients were classified as ‘low prognosis’ according to the POSEIDON criteria. Overall in all four groups Clinical Pregnancy rate was approximately 20.6% in low prognosis patients who underwent fresh ET. Conclusion: Providing IVF pregnancy with autologous oocytes to low ovarian responders is the most challenging part of fertility care. The new POSEIDON concept is helping the clinicians in medical management and in counselling patients what to expect, helping in reducing time to pregnancy.

We present the case of a young primigravida, conceived with in vitro fertilisation, referred with unilateral neck swelling and pleuritic chest pain. Our case highlights the potential complexity of the management of the complications of assisted conception techniques. The discussion explores important considerations in the management of such patients.

Maternal adnexal torsion in pregnancy, with a reported incidence of 1–10 per 10,000 spontaneous pregnancies, is very uncommon. Since it has been described as a severe complication after controlled ovarian hyper-stimulation for in vitro fertilization (IVF), it is more common in IVF pregnancies. This condition mainly occurs in the first trimester; it is rare during the late second trimester. Conservative management of adnexal torsion by laparoscopy is extended for the management of such conditions during pregnancy. An enlarged uterus could cause operational difficulties in the second trimester. In this paper, we report a case of adnexal torsion in a twin, 23 weeks with IVF pregnancy, that was successfully untwisted by laparoscopy.

This study evaluated a questionnaire originally developed for use with health professionals to explore and compare patients' and clinicians' perceptions of elective single embryo transfer and twin births.IVF clinicians and patients attending an independent Fertility clinic were surveyed using the Attitudes to a twin birth scale (ATIPS) comprising two subscales: attitudes to twins (A-Twin) and attitudes to elective single embryo transfer (A-SET). After refinement total sample scores showed both subscales were reliable with Cronbach's alpha0.8 and item-total correlations0.35.Questionnaires were completed by 100 female IVF patients and 17 IVF clinicians. A-Twin subscale scores indicated neither the IVF clinicians nor female IVF patients demonstrated very positive attitudes to a twin birth although the IVF female patients were more in favour (t = 5.29, n = 117, p =0.001). Responses suggest both groups would benefit from increased information about the risks of a twin birth for the baby. First cycle IVF female patients were significantly more positive about eSET (z = 3.94, n = 100, p = 0.001). Clinicians perceive both their colleagues' and female patients' negativity towards eSET; suggesting a role for education.This study found the ATIPS to be a reliable measure which could be useful in evaluating interventions to promote single embryo transfer.

The aetiology of Oculo-Auriculo-Vertebral Spectrum (OAVS) is unkown. We report a case following a prenatal diagnosis of 45,X/46,XY mosaicism in a pregnancy achieved by In-Vitro Fertilization (IVF) and describe evidence for the interrelationships of these phenomena and multiple births. This report extends the phenotypes associated with prenatally diagnosed 45,X/46,XY mosaicism and supports the association of OAVS and IVF.

IVF programmes generally follow treatment protocols that strive for best outcomes. Deviations from such established protocols, even if conceptionally well supported, always risk potentially adverse effects on pregnancy chances. Successful pregnancy represents, however, the principal motivation for all fertility treatments. As a universal medical principle, patients are, therefore, entitled to maximal professional efforts towards their desired outcomes in the safest, quickest and most cost-effective ways. For IVF this means, as multiple patient queries in the literature have demonstrated, the following parameters in this order of importance: highest possible pregnancy rates, lowest possible risks, shortest possible time and lowest possible cost. Some recently widely propagated changes to broadly utilized practice patterns in IVF now, post factum, have been determined to be clinically useless and, in addition, have been shown to adversely affect pregnancy chances. Also post factum, this has led to the acknowledgement that significant modifications to established IVF practice should be introduced with caution. In view of the quite satisfactory IVF pregnancy rates that are currently achieved, the uncontrolled introduction of significant protocol modifications, which may adversely affect IVF outcomes, should no longer be acceptable practice as such unproven practice modifications may violate the patient's entitlement to maximally achievable pregnancy rates.

This study was designed to examine the effect of bacterial contamination on in vitro fertilization treatment outcomes.In a prospective clinical trial, 152 patients aged 23-38 years, mean 33.3 +/- 4.6, undergoing IVF treatment were selected for this study. During embryo transfer, separate samples were collected for microbial examination from the following sites: the fundus of the vagina, the cervix, the embryo culture medium prior and post-embryo transfer, the tip of the catheter, and the external sheet. All the samples were separately cultured to identify any bacteria or yeast present.Pregnancy rates in patients testing positive for Entrobacteriaceae (22.2% versus 51%) and Staphylococcus species (17.6% versus 44%) were significantly lower than those in the negative culture group (p0.001). The pregnancy rates do not seem to be affected by the other isolated microorganisms.This study shows that the presence of vaginal-cervical microbial contamination at the time of embryo transfer is associated with significantly decreased pregnancy rates.

The laparoscopic excision of ovarian endometriomas appears to increase the chances of spontaneous conception, but the value of this treatment in women selected for IVF-ICSI cycles is debated. Studies recruiting women with unilateral disease and comparing ovarian responsiveness in the affected and contralateral intact gonads indicate that excision of endometriomas is associated with a quantitative damage to ovarian reserve. There are no randomized trials comparing laparoscopic excision to expectant management before IVF-ICSI cycles. The idea that surgery increases IVF pregnancy rates is not supported by the available evidence. However, the chance of conception is not the only issue that has to be considered. Some potential drawbacks are associated with both therapeutical strategies. Specifically, costs and hazard of surgical complications support expectant management whereas oocyte retrieval risks, the possibility of missing occult malignancy and endometriosis progression due to ovarian stimulation would favour surgical treatment. Alternative therapeutical options include medical treatment and ultrasound-guided aspiration. Whereas prolonged GnRH agonist down-regulation may be beneficial, data on ultrasound aspiration are more controversial.

Although Edwards and Steptoe achieved the first IVF pregnancy and birth in 1978, the majority of pioneering developments in IVF during the eighties came from Australia. They included the world's first donor egg pregnancy, the first frozen embryo pregnancy and the first IVF multiple pregnancies. Australia also produced the first national guidelines for IVF practices, the first statute legislation protecting donor gamete pregnancies, and Victoria proclaimed the first statute legislation regarding control of IVF procedures. The reporting of the outcome of all IVF pregnancies began in 1980 as another world initiative.