When only one embryo is available, is it better to transfer on Day 3 or to grow on?

RESEARCH QUESTION: In patients with only one embryo on Day 3 post-IVF treatment, does transferring the embryo into the uterine environment achieve a higher pregnancy rate than growing the embryo on with a plan to transfer at Day 4-6? DESIGN: This was a retrospective cohort study conducted in patients with only one viable embryo on Day 3 post-IVF treatment. Data were extracted from a standardized IVF database and included 1384 women who fulfilled this study's selection criteria. Outcomes of these embryos were followed up and stratified into two groups: embryos transferred on Day 3 and those grown on to Day 4-6. Pregnancy rate (biochemical and clinical) and live birth rates were analysed with logistic regression and adjusted using a parsimonious model for baseline patient characteristics. RESULTS: Biochemical pregnancy (16.7% versus 9.5%, odds ratio [OR] 1.9, P = 0.001), clinical pregnancy (14.7% versus 6.8%, OR 2.35, P < 0.001) and live birth rates (9.7% versus 4.4%, OR 2.37, P = 0.002) were significantly higher in the Day 3 group than those in the group grown on to Day 4-6. These differences were still significant after adjusting for potential confounders (adjusted OR 2.60, 3.71, 4.08, respectively, P < 0.001). CONCLUSIONS: These findings support Day 3 cleavage-stage embryo transfer instead of growing on to Day 4-6 for blastocyst-stage transfer when only a single embryo is available.

Management of non-tubal ectopic pregnancies at a large tertiary hospital.

There are limited data on the management of non-tubal ectopic pregnancies (NTEP). We reviewed the management of these cases at a tertiary centre with a dedicated institutional protocol. All cases of confirmed NTEP were retrospectively identified from 2006 to 2014. Records were reviewed for presenting features, mode and success of initial management, preservation of fertility and length of hospital stay. The main outcome measure was the success rate of medical management with methotrexate. The 60 cases identified included 34 cornual, 14 Caesarean section scar, nine cervical and three cervical involving previous Caesarean scar. Primary surgical management was performed in 22 patients. Thirty-eight patients received medical therapy with single or multidose methotrexate. Successful medical management was observed in 33 (87%); however, length of stay was significantly longer compared with surgical patients (mean 14 ± 12 days versus 5 ± 2 days, P < 0.01). Hysterectomy was performed in three patients (one surgical group, two medical group). There was one case of methotrexate toxicity with no long-term adverse outcome. Medical management of NTEP is a safe first-line therapy for clinically stable patients desiring preservation of fertility despite a longer period of inpatient monitoring and follow-up.

Ovarian hyperstimulation syndrome: A case control study investigating risk factors.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a complication of in vitro fertilisation (IVF) treatment associated with significant morbidity and mortality. AIMS: To assess the severity of OHSS in patients admitted to a tertiary hospital in Melbourne, Australia, and identify risk factors for the condition. MATERIAL AND METHODS: The files of patients admitted with OHSS over a five-year period between 2008 and 2013 were reviewed. Baseline characteristics of OHSS patients were compared with IVF patients who did not develop OHSS to establish risk factors for the OHSS patient group. Relative risk was estimated using multivariate Poisson regression. A risk score was then developed using the coefficients from the Poisson regression to aid identification of patients at high risk for the condition. RESULTS: The following risk factors were associated with an increased risk of developing OHSS: younger age, higher oestradiol (E2) concentration (relative risk (RR) 1.43, P < 0.001), and higher follicle count (RR 1.40, P < 0.001). Lower body mass index (BMI) was not correlated with an increased risk of developing OHSS (RR 1.1, P = 0.19). CONCLUSIONS: This study demonstrates that a risk score can be calculated from routinely taken measurements to identify patients at high risk of OHSS. Using this risk score could help clinicians reduce the incidence of OHSS by employing preventative strategies in high-risk patients.

Do women with ovaries of polycystic morphology without any other features of PCOS benefit from short-term metformin co-treatment during IVF? A double-blind, placebo-controlled, randomized trial.

BACKGROUND: Women with ovaries of polycystic morphology (PCO), without any other features of polycystic ovary syndrome (PCOS), respond similarly to women with PCOS when stimulated with exogenous gonadotrophins, and both groups share various endocrinological disturbances underlying their pathology. In women with PCOS, metformin co-treatment during IVF has been shown to increase pregnancy rates and reduce the risk of ovarian hyperstimulation syndrome (OHSS). The aim of this study was to investigate whether metformin co-treatment before and during IVF can also increase the live birth rate (LBR) and lower severe OHSS rates for women with PCO, but no other manifestations of PCOS. METHODS: This study was a double-blind, multi-centre, randomized, placebo-controlled trial. The study population included 134 women with ovulatory PCO (and no evidence of clinical or biochemical hyperandrogenism) undergoing IVF treatment at three tertiary referral IVF units. The primary outcome was LBR. RESULTS: In total, 134 women were randomized, 69 to metformin and 65 to placebo. There were no statistically significant differences between the two groups in baseline characteristics. With regard to IVF outcome, no significant improvements were found in the metformin group when compared with the placebo group. In particular, there was no difference between the groups in rates of live birth [metformin n = 27 (39.1%), placebo n = 30 (46.2), (95% confidence interval 0.38, 1.49, odds ratio = 0.75)], clinical pregnancy [metformin n = 29 (42.0%), placebo n = 33 (50.8%)] or severe OHSS [metformin n = 6 (8.7%), placebo n = 5 (7.7%)]. CONCLUSIONS: There appears to be no benefit in metformin co-treatment before and during IVF in women with PCO without any other features of PCOS. Clinical Trials.gov: NCT01046032.

Preimplantation Genetic Testing for Aneuploidy: A Review.

IMPORTANCE: Preimplantation genetic testing for aneuploidy (PGT-A) has undergone many technical developments over recent years, including changes in biopsy timings, methodology, and genetic analysis techniques. The evidence surrounding the efficaciousness of PGT-A is sporadic and inconsistent; as such, significant doubt and concern remain regarding its widespread implementation. OBJECTIVE: This review seeks to describe the historical development of PGT-A and to analyze and summarize the current published literature. CONCLUSIONS: At times during its infancy, PGT-A failed to display conclusive improvements in results; with newer technologies, PGT-A appears to yield superior outcomes, including reductions in miscarriages and multiple gestations. Clinicians and patients should assess the use of PGT-A on a case-by-case basis, with laboratories encouraged to utilize blastocyst biopsy and next-generation sequencing when conducting PGT-A. Further studies providing cumulative live birth rates and time to live birth are required if PGT-A is to be proven as producing superior outcomes. RELEVANCE: PGT-A has the potential ability to impact in vitro fertilization success rates, and as it is increasingly adopted worldwide, it is crucial that clinicians are aware of the evidence for its continued use.

Gonadotropin-Releasing Hormone-Agonist Triggering and a Freeze-All Approach: The Final Step in Eliminating Ovarian Hyperstimulation Syndrome?

IMPORTANCE: In vitro fertilization (IVF) has evolved dramatically in recent decades; however, clinical practices have been slow to adopt these advancements, particularly regarding final oocyte maturation and the timing of embryo transfer. Concerns still exist over the ability of gonadotropin-releasing hormone (GnRH) agonists and elective embryo cryopreservation to reduce the risk of ovarian hyperstimulation syndrome (OHSS) without compromising pregnancy outcomes. OBJECTIVE: This review investigates IVF outcomes associated with GnRH-agonist triggering and elective embryo cryopreservation. The safety and efficacy of GnRH-agonist triggering are compared with conventional human chorionic gonadotropin triggering, and frozen embryo transfers are weighed against fresh transfers. EVIDENCE ACQUISITION: A literature search was conducted using OVID (MEDLINE) and PubMed databases. The search strategy included keywords such as "ovarian hyperstimulation syndrome or OHSS," "GnRH-agonist triggering," "cryopreservation or freeze-all," and "IVF outcomes." A total of 214 articles were considered for review. RESULTS: Gonadotropin-releasing hormone agonist triggering reduces OHSS incidence without compromising oocyte retrieval and fertilization rates in donor and autologous cycles. However, GnRH-agonist triggering causes a luteal phase deficiency in autologous cycles, deleteriously compromising pregnancy rates. Elective embryo cryopreservation overcomes this deficiency, reducing the risk of OHSS and may improve neonatal and obstetric outcomes. CONCLUSIONS: Gonadotropin-releasing hormone agonist triggering should be considered in all donor cycles. It should also be selectively considered in autologous cycles in combination with elective cryopreservation of all viable embryos.

Female obesity and infertility.

Infertility affects one in seven couples, and its rate is on the increase. Ovulatory defects and unexplained causes account for >50% of infertile aetiologies. It is postulated that a significant proportion of these cases are either directly or indirectly related to obesity. The prevalence of overweight and obese men and women has topped 50% in some developed countries. Obesity is on the increase worldwide; in turn, the consequences in terms of the associated morbidity and mortality have also been increasing. Obesity is associated with various reproductive sequelae including anovulation, subfertility and infertility, increased risk of miscarriage and poor neonatal and maternal pregnancy outcomes. Thus, the combination of infertility and obesity poses some very real challenges in terms of both the short- and long-term management of these patients. The mechanism with which obesity impacts female reproductive function is summarised in this review.

Cryopreserved oocytes: update on clinical applications and success rates.

IMPORTANCE: Over the past 3 decades, oocyte cryopreservation procedures have improved rapidly. However, there is limited research reviewing the efficacy of different cooling protocols and inadequate data comparing in vitro fertilization (IVF) outcomes from fresh oocytes with cryopreserved oocytes. OBJECTIVE: The present review was performed to investigate advances in oocyte cryopreservation technologies and identify areas for further research, to determine whether results from IVF using cryopreserved oocytes are comparable to IVF using fresh oocytes, and to identify the patient populations requiring access to oocyte cryopreservation. EVIDENCE ACQUISITION: A literature review was conducted. OVID (MEDLINE) and PubMed databases were queried using phrases such as "oocyte or egg" and "cryopreservation," "vitrification," or "slow cooling or slow freezing." A total of 180 studies were selected for review. RESULTS: Current literature suggests that vitrified oocytes produce superior IVF results to slow-frozen oocytes and may yield comparable outcomes to IVF with fresh oocytes in certain patient populations. Patients at risk of infertility due to disease or age-related decline or oocyte donation programs, couples who fail to produce semen when required for IVF, and patients with legal or ethical reasons against embryo cryopreservation may access cryopreserved oocytes. CONCLUSIONS: We suggest that women who comprise the previously mentioned patient populations should be offered oocyte vitrification technology. Further research is required to confirm IVF success across all patient populations and determine the best cryopreservation protocols. RELEVANCE: This review will be relevant to clinicians interested in fertility treatments using cryopreserved oocytes, fertility preservation, oncology and fertility, and immunology and fertility.

Defining the relationship between fetal Doppler indices, abdominal circumference and growth rate in severe fetal growth restriction using functional linear discriminant analysis.

The relationship between Doppler measurements, size and growth rate in fetal growth restriction has not been defined. We used functional linear discriminant analysis (FLDA) to investigate these parameters taking account of the difficulties inherent in exploring relationships between repeated observations from a small number of cases. In 40 fetuses with severe growth restriction, serial abdominal circumference (AC), umbilical, middle cerebral artery (MCA) and ductus venosus Doppler pulsatility index measurements were recorded. In 11 singleton fetuses with normal growth, umbilical artery pulsatility index only was measured. Data were expressed as z-scores in relation to gestation and analysed longitudinally using FLDA. In severe growth restriction, the Spearman correlation coefficients between umbilical artery pulsatility index and AC z-score, MCA pulsatility index and AC z-score and ductus venosus pulsatility index z-score and AC z-score were, respectively: -0.36, p = 4.4 × 10(-7); 0.70, p = 1.1 × 10(-17) and -0.50, p = 8.1 × 10(-4). No relationship was seen between Doppler parameters and growth rate. There was no relationship between umbilical artery pulsatility index and AC nor growth rate in normally grown fetuses. In severe fetal growth restriction, Doppler changes are related to absolute fetal AC size, not growth rate.

Corifollitropin alfa for female infertility.

INTRODUCTION: Follicle-stimulating hormone (FSH) is essential for the development of ovarian follicles. Urinary-derived and recombinant FSH (rFSH) preparations are widely used in infertility treatment but have to be administered daily to achieve steady-state serum levels. Corifollitropin alfa is a hybrid molecule with a prolonged half-life. AREAS COVERED: The development and clinical testing of corifollitropin alfa, including the pharmacodynamics and kinetics, efficacy and drug safety. Searches were performed using the Medline database. EXPERT OPINION: Corifollitropin alfa is composed of the FSH α-subunit and a hybrid of the FSH ß-subunit and the C-terminal peptide (CTP) of the human chorionic gonadotropin (hCG) ß-subunit. The rationale of developing such a molecule was to reduce patient burden, by reducing the number of injections required to sustain multifollicular growth. Two strengths of corifollitropin are available (for patients ≤ 60 kg and > 60 kg). Compared with a daily dose of 200 IU of rFSH, 150 mcg of corifollitropin is equivalent in safety and pregnancy outcomes in women > 60 and < 90 kg using an antagonist protocol. Another RCT in women ≤ 60 kg also confirmed safety and efficacy of follicular stimulation (100 mcg of corifollitropin versus 150 IU of rFSH), but it was not powered to demonstrate equivalence in terms of pregnancy rates.