Neither male age nor semen parameters influence clinical pregnancy or live birth outcomes from IVF

Advanced age is an increasing trend for both males and females seeking in vitro fertilization (IVF). This retrospective cohort study investigated the outcomes of 1280 IVF-related treatment cycles, selecting the first treatment for couples utilizing autologous gametes and who underwent single fresh embryo transfer. Males aged 40–49 years had a 52% reduction in normal sperm motility, while it was markedly reduced by 79% at 50 years or older. However, neither semen parameters nor male age were predictive of clinical pregnancy or live birth chance. In a combination of age groups, cases with Younger Females had the greatest chance of successful outcomes and this was independent of having a younger or older male partner. Specifically, Young Female-Young Male combinations (≤ 35 years) were the most likely to succeed in achieving a clinical pregnancy or live birth (OR 2.84, p?<?0.0005 and 3.34, p?<?0.0005, respectively), while the Young Female-Old Male group (≤ 35 and >35 years, respectively) had a similar increased chance (OR 2.07, p?<?0.0005 and 2.78, p?<?0.0005, respectively). This trend strengthened as the Female age cut-off was increased to 38 years and the Male age cut-off increased to 40 or 42 years. Consistently, the groups comprising a Young Female with either a Young Male or Old Male outperformed the groups with an Old Female. Our finding confirms reduced fecundity with advancing female age as the most important parameter. The outcomes were not significantly influenced by semen parameters or male age with respect to the likelihood of clinical pregnancy or live birth.     

Live Birth and Cumulative Live Birth Rates in Expected Poor Ovarian Responders Defined by the Bologna Criteria Following IVF/ICSI Treatment

ObjectiveTo determine the live birth and cumulative live birth rates of expected poor ovarian responders according to the Bologna criteria and to compare their outcomes with those of expected normal respondersDesignRetrospective analysisSettingUniversity infertility clinicPatientsA total of 1,152 subfertile women undergoing their first in vitro fertilization (IVF) cycleInterventionsWomen were classified into 4 groups according to the Bologna criteria for comparisonResultsWomen with expected poor response (POR) had the lowest live birth rate than the other 3 groups (23.8%, p = 0.031). Cumulative live birth rates were significantly lower in those with expected POR than those with expected normal ovarian response (NOR) (35.8% vs 62.8%, p<0.0001). In the subgroup analysis, the cumulative live birth rates in expected PORs were significantly lower in those who had ≤3 oocytes retrieved (18.6% for ≤3 oocytes vs 44.0% for >3 oocytes, p = 0.006) whereas the live birth rates in fresh cycle did not differ (17.8% vs 30.9%, p = 0.108).ConclusionWomen who were expected POR according to the Bologna criteria had lower live birth and cumulative live birth than expected NOR but they still can achieve reasonable treatment outcomes and IVF treatment should not be precluded.     

Role of Baseline Antral Follicle Count and Anti-Mullerian Hormone in Prediction of Cumulative Live Birth in the First In Vitro Fertilisation Cycle: A Retrospective Cohort Analysis

Objective

This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle.

Methods

We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle.

Results

Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616–0.675) and age (0.648, 95% CI 0.618–0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587–0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone.

Conclusion

Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women''s age.     

Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles

Background

The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown.

Methods and Findings

We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia.

Conclusions

Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF. Please see later in the article for the Editors'' Summary     

Founding pioneers of IVF update: Innovative researchers generating livebirths by 1982

This commentary adds accuracy and interesting information to the story of the founding pioneers of IVF which was published in this journal in 2018, at the 40^th anniversary of the first IVF livebirth, namely Louise Joy Brown born 25 July 1978. Table 1 in that first publication is now updated to reflect extended information about Team 1 comprising the acknowledged “Fathers of IVF”, but whose work is better tabulated as Team 1a from the NHS days in Oldham; and Team 1b covering the new period of private practice at Bourn Hall in Cambridge. With the passing of pioneer Ian Craft, co-author of the first article, further information came to light at his memorial service. There has now been some adjustment to the last few months of 1982, with correct inclusion of Israel into the list along with an interesting exposé of the two major pioneer facilities of that country. The previously cited third Australian groups (Team 12) have now been appropriately relegated to 1983, a year which experienced a plethora of IVF facilities around the world and the beginning of the IVF population boom.     

Birth of the Japanese Monkey (Macaca fuscata) infant following in-vitro fertilization and embryo transfer

The first successful birth by in-vitro fertilization (IVF) and embryo transfer (ET) in the Japanese monkey was described. IVF was carried out by using oocytes collected after ovarian stimulation and sperms collected by rectal electro-ejaculation. The embryos were incubated for 36–66 hours and then transferred to the fallopian tube of the recipient via the fimbria under laparoscopic observations. Four recipients received their own embryos and six recipients received donor embryos. Two recipients of six that received donor embryos became pregnant after receiving one 3-cell and one 2-cell embryos, and one 4-cell and one 2-cell embryos, respectively. On healthy terminated male infant was delivered 166 days after ET, but the other aborted on day 128. This successful birth indicates the usefulness of our IVF/ET method for systematic indoor artificial breeding and preservation of endangered primates species.     

Elective frozen-thawed embryo transfer (FET) in women at risk for ovarian hyperstimulation syndrome

Elective cryopreservation of cultured embryos has become a treatment option for women at risk for ovarian hyperstimulation syndrome (OHSS). The aim of our study was to investigate the outcome of elective cryopreservation and consecutive frozen-thawed embryo transfer (FET) in a large IVF clinic in Austria. A total of 6104 controlled ovarian hyperstimulation cycles (COH) were performed on 2998 patients including 200 patients (6.7%) who were undergoing elective cryopreservation and FET due to high risk of OHSS. We estimated the cumulative live birth rate using the Kaplan-Meier method and evaluated independent predictors for successful live births with a Cox model. A total of 270 frozen-thawed embryo transfers were performed on 200 patients with up to 4 transfers per patient. The first embryo transfer showed a live birth rate of 42.0%, the second transfer showed a cumulative rate of 58.5%. After a total of 4 FETs from the same COH cycle, a cumulative live birth rate of 61.0% per COH cycle could be achieved. Four cases of OHSS occurred amongst these patients (2.0%), all of them of moderate severity. Multivariate analysis identified maternal age, the use of assisted hatching and the number of embryos transferred at the blastocyst stage as independent predictors for cumulative live birth. Our study clearly suggests that elective FET is safe and shows excellent cumulative live birth rates. This concept can, therefore, be used to avoid the severe adverse events caused by COH and the inefficient use of cultured embryos.     

Anti-Müllerian hormone (AMH) is a strong predictor of live birth in women undergoing assisted reproductive technology

In the present study, we evaluated the clinical value of the following parameters: basal anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B and antral follicle count (AFC) in predicting live birth outcomes. The study involved 603 women undergoing in vitro fertilization (IVF) using the long protocol for controlled ovarian hyperstimulation (COH). Serum levels of AMH, FSH and inhibin B as well as AFC were measured on the first three days of the menstrual cycle prior to the beginning of stimulation. AMH was the only independent parameter that correlated with the chance of live birth. We found that live birth rates of 46.2% (patient age <35 years), 44.7% (35–37 years), 32.1% (38–39) and 15.3% (>39) were associated with concentrations of AMH > 1.4 ng/ml. For the AMH range 0.6–1.4 ng/ml, the live birth rates were 29.3%, 12.5%, 5.6% and 2.7%, respectively, and for AMH concentrations below 0.6 ng/ml the rates were 7.1%, 8.3%, 0% and 5.8%, respectively. Independently of other parameters affecting the chance of live birth, the success rate was the highest when the AMH level was >2 ng/ml, significantly lower when the AMH concentration was about 1 ng/ml, and 0% when the AMH concentration was ∼0.1 ng/ml. In conclusion, this is the first report to demonstrate that AMH level correlated better than age, FSH or inhibin B concentrations or AFC with live birth outcome. Therefore, the basal serum concentration of AMH may become a new, substantial prognostic factor regarding live birth above and beyond other currently available predictors of IVF outcome.     

Amino acid profiles in first trimester amniotic fluids of healthy bovine cloned pregnancies are similar to those of IVF pregnancies,but not nonviable cloned pregnancies

Somatic cell nuclear transfer (SCNT), or cloning, is one of the assisted reproductive technologies currently used in agriculture. Commercial applications of SCNT are presently limited to the production of animals of high genetic merit or the production of the most elite show cattle owing to its relatively low efficiency. In current practice, 20% to 40% of SCNT pregnancies do not result in viable offspring. In an effort to better understand some of the anomalies associated with SCNT pregnancies, we investigated amino acid compositions of first trimester amniotic fluid. In this retrospective study, amniotic fluids were collected from SCNT and control IVF pregnancies at Day 75 of gestation and grouped according to the pregnancy results: control IVF (IVF), viable SCNT pregnancies that resulted in live healthy calves (SCNT-HL), nonviable SCNT pregnancies that were aborted before Day 150 (SCNT-ED), and nonviable SCNT pregnancies that were aborted after Day 150 or produced deceased calves (SCNT-LD). High-performance liquid chromatography (HPLC) was used to analyze the concentrations of 22 amino acids (AAs) in the amniotic fluid samples. There were no differences in average AA concentrations between IVF and SCNT-HL groups, whereas SCNT-LD and SCNT-ED had higher levels of total AA concentrations. Concentrations of asparagine, citruline, arginine, and valine were significantly higher in the SCNT-LD group. Both SCNT-LD and SCNT-ED groups had relatively large intragroup variances in AA concentrations. Urea concentration was also measured in the SCNT amniotic fluid samples. No correlations between urea concentrations and arginine concentrations or pregnancy outcomes were found. The findings in this study not only deepen the understanding on SCNT pregnancy anomalies, but also provide a potentially useful screening tool for assessing viable and nonviable SCNT pregnancies.     

Increasing Live Birth Rate by Preimplantation Genetic Screening of Pooled Polar Bodies Using Array Comparative Genomic Hybridization

Meiotic errors during oocyte maturation are considered the major contributors to embryonic aneuploidy and failures in human IVF treatment. Various technologies have been developed to screen polar bodies, blastomeres and trophectoderm cells for chromosomal aberrations. Array-CGH analysis using bacterial artificial chromosome (BAC) arrays is widely applied for preimplantation genetic diagnosis (PGD) using single cells. Recently, an increase in the pregnancy rate has been demonstrated using array-CGH to evaluate trophectoderm cells. However, in some countries, the analysis of embryonic cells is restricted by law. Therefore, we used BAC array-CGH to assess the impact of polar body analysis on the live birth rate. A disadvantage of polar body aneuploidy screening is the necessity of the analysis of both the first and second polar bodies, resulting in increases in costs for the patient and complex data interpretation. Aneuploidy screening results may sometimes be ambiguous if the first and second polar bodies show reciprocal chromosomal aberrations. To overcome this disadvantage, we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification. We retrospectively studied 351 patients, of whom 111 underwent polar body array-CGH before embryo transfer. In the group receiving pooled polar body array-CGH (aCGH) analysis, 110 embryos were transferred, and 29 babies were born, corresponding to live birth rates of 26.4% per embryo and 35.7% per patient. In contrast, in the control group, the IVF treatment was performed without preimplantation genetic screening (PGS). For this group, 403 embryos were transferred, and 60 babies were born, resulting in live birth rates of 14.9% per embryo and 22.7% per patient. In conclusion, our data show that in the aCGH group, the use of aneuploidy screening resulted in a significantly higher live birth rate compared with the control group, supporting the benefit of PGS for IVF couples in addition to the suitability and effectiveness of our polar body pooling strategy.     

Hospital Mental Health Admissions in Women after Unsuccessful Infertility Treatment and In Vitro Fertilization: An Australian Population-Based Cohort Study

Objective

To examine the association between in vitro fertilization (IVF) and later admission to hospital with a mental health diagnosis in women who remained childless after infertility treatment.

Methods

This was a population-based cohort study using linked administrative hospital and registry data. The study population included all women commencing hospital treatment for infertility in Western Australia between the years 1982 and 2002 aged 20–44 years at treatment commencement who did not have a recorded birth by the end of follow-up (15 August 2010) and did not have a hospital mental health admission prior to the first infertility admission (n=6,567). Of these, 2,623 women had IVF and 3,944 did not. We used multivariate Cox regression modeling of mental health admissions and compared women undergoing IVF treatment with women having infertility treatment but not IVF.

Results

Over an average of 17 years of follow-up, 411 women in the cohort were admitted to hospital with a mental health diagnosis; 93 who had IVF and 318 who did not. The unadjusted hazard ratio (HR) for a hospital mental health admission comparing women who had IVF with those receiving other infertility treatment was 0.50 (95% confidence interval [CI] 0.40–0.63). After adjustment for age, calendar year and socio-economic status the HR was 0.56 (95% CI 0.44–0.71).

Conclusions

IVF treatment is associated with a reduced risk of hospital mental health admissions in women after unsuccessful infertility treatment. This may be explained by the healthy cohort effect.     

Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis

The clinical effect of sperm DNA damage in assisted reproduction has been a controversial topic during recent decades, leading to a variety of clinical practice recommendations. While the latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta-analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE-PubMed and EMBASE databases. We included studies analysing IVF and/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI-NIH quality assessment tool was used to assess the quality of each study. Meta-analyses were conducted using the Mantel–Haenszel method with random-effects models to evaluate the Risk Ratio (RR) between high-DNA-damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I² statistic. We also conducted sensitivity analyses and post-hoc subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta-analysis, comprising 12380 IVF/ICSI cycles. Meta-analysis revealed that, considering IVF and ICSI results together, implantation rate (RR = 0.74; 95% CI = 0.61–0.91; I² = 69) and pregnancy rate (RR = 0.83; 0.73–0.94; I² = 58) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non-significant but detrimental tendency (RR = 0.78; 0.58–1.06; I² = 72) on live birth rate. Meta-analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR = 0.68; 0.52–0.89; I² = 50) and pregnancy rates (RR = 0.72; 0.55–0.95; I² = 72), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR = 0.48; 0.22–1.02; I² = 79). In the case of ICSI, non-significant trends were observed for implantation (RR = 0.79; 0.60–1.04; I² = 72) or pregnancy rates (RR = 0.89; 0.78–1.02; I² = 44), and live birth rate (RR = 0.92; 0.67–1.27; I² = 70). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and/or allow a given couple to be advised on the most suitable treatment. Further well-designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.     

Comparison of mice born after intracytoplasmic sperm injection with in vitro fertilization and natural mating

The procedures of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are routinely used in modern medicine to overcome infertility and, in animal husbandry, to propagate lines with compromised fertility. However, there remains concern that manual selection and injection of whole sperm into oocytes could contribute to pre- and postnatal developmental defects. To address this, we have used gene expression profiling and immunophenotyping to characterize offspring generated by these procedures. We used gametes from glutathione peroxidase 1 knockout (Gpx1-/-) mice as a sensitized screen responsive to oxidative stress from artificial reproduction technologies (ART). There were no differences between IVF and ICSI derived offspring in gene expression patterns, and minor differences in hematopoietic parameters. Furthermore there were only minor differences between these IVF and ICSI pups and those derived from natural mating. These data demonstrate for the first time in that there is no significant phenotypic affects of ICSI when compared to IVF and we identified a relatively minor influence of the artificial fertilization methods on phenotype of offspring compared with natural mating. These observations would support the use of ICSI for derivation of mutant mouse lines and may be of some importance for the use of this technique in human ART.     

A consistently successful procedure for in vitro fertilization of golden hamster eggs

Complete details are described for the first time of the procedures used in the author's laboratory for obtaining in vitro fertilization (IVF) of golden hamster eggs leading to the first cleavage division. These IVF procedures have been developed during the past 20 years and are very reproducible: IVF of at least 75% of eggs is routinely achieved, and on average 65% of inseminated eggs undergo the first cleavage division in vitro. These results can easily be obtained by inexperienced investigators. The ease and reproducibility of the hamster IVF procedures make them very suitable for studies of sperm:egg interaction and associated events. Studies in the author's laboratory have included analysis of sperm fertilizing ability under chemically defined conditions, the presence of sperm acrosome reaction stimulating factors in the egg investments, maturation of oocytes in vitro, the block to polyspermy, and the contribution of egg aging to fertilization anomalies. In addition, the motility of hamster sperm under chemically defined conditions is used in a routine screening protocol for detecting contaminants in the culture milieu. Golden hamster gametes of Ter several distinct advantages for IVF studies, including the large size of the sperm acrosome, the persistence of the very large sperm tail in the ooplasm for many hours following fertilization, and the translucence of the ooplasm, which facilitates observation of the sperm tail and pronuclei. The female golden hamster exhibits a regular 4 day estrous cycle, with distinctive indications of estrus and postestrus phases. Because of the advantages of using the golden hamster, the procedures described in this report may be useful to other investigators wishing to conduct research using IVF. Essentially the same IVF procedures can be used with monkey and bovine gametes.     

Four years of IVF/ICSI experience in Kampala (Uganda)

⁴Correspondence address. Zonlaan 49, 1700 Dilbeek, Belgium. E-mail: peterplatteau{at}telenet.be We all know that starting and running an ART clinic is not soeasy as some people might perceive from outside. Doing the samething in the middle of Africa is even more challenging as someevidences in the Western world are not so obvious in this partof the world. We started our clinic in Kampala in 2004. Theclinic was a converted apartment from a four flat building.In the beginning, we had difficulties with importing drugs,culture media and consumables; we had the feeling everybodywas against us. We overcame multiple power failures, night intrudersand a 20% masturbation failure, but once the first IVF/ICSIbabies were born, people started to believe in the project.At present, 250 IVF/ICSI cycles a year are done in batches,we have a successful embryo freezing programme, offer IUI/ICSIfor sero discordant HIV couples and have the first babies afterIVF, ICSI, testicular biopsy, embryo freezing, oocyte donationand surrogacy in Central Africa. The results are comparableto the ones in the Western world.     

Preimplantation Genetic Diagnosis and Natural Conception: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Associated with Translocation

Background

Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations, and abnormal embryonic karyotypes. The number of centers performing preimplantation genetic diagnosis (PGD) for patients with translocations has steadily increased worldwide. The live birth rate with PGD was reported to be 27-54%. The live birth rate with natural conception was reported to be 37-63% on the first trial and 65-83% cumulatively. To date, however, there has been no cohort study comparing age and the number of previous miscarriages in matched patients undergoing or not undergoing PGD. Thus, we compared the live birth rate of patients with RPL associated with a translocation undergoing PGD with that of patients who chose natural conception.

Methods and Findings

After genetic counseling, 52 patients who desired natural conception and 37 patients who chose PGD were matched for age and number of previous miscarriages and these comprised the subjects of our study. PGD was performed by means of fluorescence in situ hybridization analysis. The live birth rates on the first PGD trial and the first natural pregnancy after ascertainment of the carrier status were 37.8% and 53.8%, respectively (odds ratio 0.52, 95% confidence interval 0.22-1.23). Cumulative live birth rates were 67.6% and 65.4%, respectively, in the groups undergoing and not undergoing PGD. The time required to become pregnancy was similar in both groups. PGD was found to reduce the miscarriage rate significantly. The prevalence of twin pregnancies was significantly higher in the PGD group. The cost of PGD was $7,956 U.S. per patient.

Conclusions

While PGD significantly prevented further miscarriages, there was no difference in the live birth rate. Couples should be fully informed of the similarity in the live birth rate, the similarity in time to become pregnancy, the advantages of PGD, such as the reduction in the miscarriage rate, as well as its disadvantages, such as the higher cost, and the advantages of a natural pregnancy, such as the avoidance of IVF failure. The findings presented here should be incorporated into the genetic counseling of patients with RPL and carrying a translocation.     

Placental imprinting variation associated with assisted reproductive technologies and subfertility

Infertility affects one in 6 couples in developed nations, resulting in an increasing use of assisted reproductive technologies (ART). Both ART and subfertility appear to be linked to lower birth weight outcomes, setting infants up for poor long-term health. Prenatal growth is, in part, regulated via epigenetically-controlled imprinted genes in the placenta. Although differences in DNA methylation between ART and control infants have been found, it remains unclear whether these differences are due to the ART procedures or to the underlying parental subfertility and how these methylation differences affect imprinted gene expression. In this study, we examined the expression of 108 imprinted genes in placental tissues from infants born to subfertile parents (n = 79), matched naturally-conceived controls (n = 158), and infants conceived using in vitro fertilization (IVF, n = 18). Forty-five genes were identified as having significantly different expression between the subfertile infants and controls, whereas no significant differences were identified between the IVF and control groups. The expression of 4 genes—IGF2, NAPIL5, PAX8-AS1, and TUBGCP5—was significantly downregulated in the IVF compared with the subfertile group. Three of the 45 genes significantly dysregulated between subfertile and control placentae—GRB10, NDN, and CD44 —were found to have a significant positive correlation between expression and birth weight. Methylation levels for these 3 genes and 4 others—MKRN3, WRB, DHCR24, and CYR61—were significantly correlated with expression. Our findings indicate that epigenetic differences in placentas resulting from IVF pregnancies may be related to the underlying subfertility in parents using IVF rather than the IVF procedure itself.     

Preimplantation genetic diagnosis in Saudi Arabia

Preimplantation genetic diagnosis (PGD) testing is the practice of obtaining a cellular biopsy sample from a developing human oocyte or embryo, acquired via a cycle of in vitro fertilization (IVF); evaluating the genetic composition of this sample; and using this information to determine which embryos will be optimal for subsequent uterine transfer. PGD has become an increasingly useful adjunct to IVF procedures. The ability to provide couples who are known carriers of genetic abnormalities the opportunity to deliver healthy babies has opened a new frontier in reproductive medicine. The purpose of the PGD is enables us to choose which embryos will be implanted into the mother. In the present study 137 families who had undergone IVF at Habib Medical Centre, were enrolled for the PGD analysis. The couple visited the clinic for the sex selection, recurrent fetal loss and with the recurrent IVF failure. 802 embryos were tested by the biopsy method and 512 are found to be normal and 290 were abnormal embryos. In this study only 24% of the embryos were transferred and the remaining was not transferred because of the abnormalities or undesired sex of the embryos. The structural and numerical abnormalities were found to be 16.8%.     

External Validation and Calibration of IVFpredict: A National Prospective Cohort Study of 130,960 In Vitro Fertilisation Cycles

Background

Accurately predicting the probability of a live birth after in vitro fertilisation (IVF) is important for patients, healthcare providers and policy makers. Two prediction models (Templeton and IVFpredict) have been previously developed from UK data and are widely used internationally. The more recent of these, IVFpredict, was shown to have greater predictive power in the development dataset. The aim of this study was external validation of the two models and comparison of their predictive ability.

Methods and Findings

130,960 IVF cycles undertaken in the UK in 2008–2010 were used to validate and compare the Templeton and IVFpredict models. Discriminatory power was calculated using the area under the receiver-operator curve and calibration assessed using a calibration plot and Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of reliability and resolution, were calculated to assess overall accuracy. Both models were compared after updating for current live birth rates to ensure that the average observed and predicted live birth rates were equal. The discriminative power of both methods was comparable: the area under the receiver-operator curve was 0.628 (95% confidence interval (CI): 0.625–0.631) for IVFpredict and 0.616 (95% CI: 0.613–0.620) for the Templeton model. IVFpredict had markedly better calibration and higher diagnostic accuracy, with calibration plot intercept of 0.040 (95% CI: 0.017–0.063) and slope of 0.932 (95% CI: 0.839–1.025) compared with 0.080 (95% CI: 0.044–0.117) and 1.419 (95% CI: 1.149–1.690) for the Templeton model. Both models underestimated the live birth rate, but this was particularly marked in the Templeton model. Updating the models to reflect improvements in live birth rates since the models were developed enhanced their performance, but IVFpredict remained superior.

Conclusion

External validation in a large population cohort confirms IVFpredict has superior discrimination and calibration for informing patients, clinicians and healthcare policy makers of the probability of live birth following IVF.