Impact of double trophectoderm biopsy on reproductive outcomes following single euploid blastocyst transfer.

OBJECTIVES: To study the effect of double trophectoderm biopsy on clinical outcomes following single euploid blastocyst transfer. STUDY DESIGN: Retrospective cohort study of 2046 single euploid frozen-thawed blastocyst transfers from January 2015 to June 2022 in a single centre. All patients undergoing a frozen-thawed embryo transfer (FTET) cycle with euploid blastocysts, biopsied for any indication, were included. The outcomes were compared for blastocysts which were biopsied and vitrified once (Group 1, n = 1684), biopsied once but vitrified twice (Group 2, n = 312) and biopsied and vitrified twice (Group 3n = 50). We adjusted for confounders and performed subgroup analysis for PGT-A, PGT-M and PGT-SR cycles. The primary outcome was live birth rate. Secondary outcomes included pregnancy, clinical pregnancy, birthweight and sex ratio. RESULTS: After adjusting for confounders (previous failed euploid implantations, embryo quality and day of biopsy), embryos which were biopsied twice had lower OR for clinical pregnancy (0.48, CI 0.26-0.88, p = 0.019) and for live birth (0.50 CI 0.27-0.92, p = 0.025) compared to controls. Embryos which were biopsied once but vitrified twice had no different ORs for all reproductive outcomes compared to controls. No significant difference was observed for neonatal birthweight or sex ratio amongst the three groups. This is a retrospective single centre study with inherent bias and results may not be transferable to all settings. CONCLUSION: This study is the largest to date assessing the outcomes of FTET cycles following double trophectoderm biopsy. The results are in keeping with the existing literature and can be incorporated into patient counselling. Whilst double biopsy seems to adversely impact LBR, it is only one of the many factors that can affect success rates. The subfertility background and embryo characteristics should not be overlooked. This study provides reassuring evidence since double biopsied embryos still result in live births with no difference in sex ratio or birthweight. However, long term follow up of the off-springs is lacking and should be reported in future studies.

A Comparative Analysis of Outcomes Between Two Different Intramuscular Progesterone Preparations in Women Undergoing Frozen Embryo Transfer Cycles.

Background: The purpose of the current study was to assess if luteal support with intramuscular (IM) 17 alpha-hydroxyprogesterone caproate (17-OHPC) (Lentogest, IBSA, Italy) improves the pregnancy outcome in comparison to natural intramuscular progesterone (Prontogest, AMSA, Italy) when administered to recipients in a frozen embryo transfer cycle. Methods: A retrospective comparative study was performed to evaluate outcomes between two different intramuscular regimens used for luteal support in frozen embryo transfer cycles in patients underwent autologous in vitro fertilization (IVF) cycles (896 IVF cycles) and intracytoplasmic sperm injection (ICSI) who had a blastocyst transfer from February 2014 to March 2017 at the Centre for Reproductive and Genetic Health (CRGH) in London. Results: The live birth rates were significantly lower for the IM natural progesterone group when compared to 17-OHPC group (41.8% vs. 50.9%, adjusted OR of 0.63 (0.31-0.91)). The miscarriage rates were significantly lower in the 17-OHPC group compared to the IM natural progesterone group (14.5% vs. 19.2%, OR of 1.5, 95% CI of 1.13-2.11). The gestational age at birth and birth weight were similar in both groups (p=0.297 and p=0.966, respectively). Conclusion: It is known that both intramuscular and vaginal progesterone preparations are the standard of care for luteal phase support in women having frozen embryo transfer cycles. However, there is no clear scientific consensus regarding the optimal luteal support. In this study, it was revealed that live birth rates are significantly higher in women who received artificial progesterone compared to women who received natural progesterone in frozen embryo transfer cycles.

Does Early-Period Patient Dissatisfaction Turn Into Satisfaction Over Time After Total Knee Replacement?

BACKGROUND Total knee arthroplasty (TKA) is frequently used in the treatment of end-stage gonarthrosis, and the patient satisfaction rate varies. This study aimed to reveal the change in mid-term patient satisfaction results and functional scores of patients with low early postoperative satisfaction scores. MATERIAL AND METHODS We included 163 patients who underwent total knee prosthesis between September 2017 and February 2018. Among these patients, early (6 months) and mid-term (24 months) satisfaction and functional results of 34 patients with low satisfaction scores (Likert evaluations 1, 2, and 3) were evaluated. We assessed early-term functional results and satisfaction rates, mid-term analysis of patients who were not satisfied in the early period, and the relationship between functional scores and satisfaction. RESULTS The Likert score was 4 or 5 in 124 (80%) of 158 patients, and early dissatisfaction was detected in 34 patients (20%). In the early-period dissatisfied group, satisfaction scores 6 months after surgery were 1.9±1.1 (1-3) and 4.2±1 (3-5) 24 months after surgery. A statistically significant difference was observed between the dissatisfied group's early and mid-term KSS and KS values. A correlation was observed between satisfaction scores and KS and KSS scores (P<0.05). CONCLUSIONS Patients who do not have mechanical problems with total knee arthroplasty but are not satisfied with the surgery in the early period can be satisfied over time after regular follow-up, appropriate communication and information, and effective rehabilitation.

The Fate of Failed Debridement, Antibiotics, and Implant Retention in Infected Knee Arthroplasties: Nothing to Lose.

Purpose The frequency of periprosthetic knee infections increases yearly because of the popularity of the total knee prostheses. Revision knee arthroplasty is an annoying problem for both the surgeons and the patients. Debridément, antibiotics, and implant retention (DAIR) is a popular alternative for the treatment of periprosthetic knee infections. Little is known about the fate of the failed DAIR patients. This study aims to investigate the effect of the failed DAIR on the clinical result after two-staged revision arthroplasty. Method Ninety-nine two-staged revision arthroplasties and 85 DAIR patients from two reference clinics were retrospectively analyzed. The minimum follow-up was 36 months. Patients were grouped according to the treatment as, two-staged revision without DAIR, two-staged revision after failed DAIR, and successful DAIR. Their Knee Society Scores (KSS), functional KSS (KSS-f) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were analyzed and compared. Results DAIR has a 52.9% success rate for the treatment of infection. Elevated erythrocyte sedimentation rates and C-reactive peptide levels are not risk factors for failure, but the time passed since the index surgery is a risk factor for worse outcome scores. Failed DAIR is not a risk factor for reinfection after two-staged revision. Last KSS after failed DAIR, successful DAIR, and two-staged revision were 83.98±7.033, 91.89±4.386, and 91.38±4.735, respectively. Last KSS-f after failed DAIR, successful DAIR, and two-staged revision were 86.25±9.524, 94.56±8.106, and 94.85±5.996, respectively. Last WOMAC after failed DAIR, successful DAIR, and two-staged revision were 86.16±7.745, 94.750±4.964, and 93.319±5.961, respectively.  Conclusion Failed DAIR is associated with lesser, but still good, or excellent clinical scores. DAIR is suggested as a promising treatment option for periprosthetic knee infections in well-selected patients.

Effects of Nesfatin-1 on Food Intake and Hyperglycemia.

Nesfatin-1 is a peptide derived from nucleobindin-2 and involved in the regulation of food intake and hyperglycemia. Nesfatin-1 is a recently described anorexigenic peptide, which may be involved in weight loss, malnutrition, and the regulation of appetite. Nesfatin-1 has an effect on the regulation of glucose homeostasis as well as that of food intake. The aim of this article is to bring a different perspective to the readers on the effects of nesfatin-1 on food intake and hyperglycemia. The central injection of nesfatin-1 may produce anorexigenic effects. The circulating level of nesfatin-1 is thought to be regulated by nutritional status. Long-term changes in body weight can affect nesfatin-1 levels. In overweight and obese individuals, nesfatin-1 levels may increase. Nesfatin-1 is synthesized in the hypothalamic appetite control regions. Nesfatin-1 levels may decrease in individuals with diabetes but may increase in those with impaired glucose tolerance. Nesfatin-1 may have a reducing effect on glucose levels. In addition, an increase in glucose levels may lead to an increase in the release of nesfatin-1 from pancreatic cells. Injection of nesfatin-1 can prevent hepatic glucose formation and stimulate glucose uptake. Reduction of hypothalamic nesfatin-1 levels increases hepatic glucose flow and decreases glucose uptake from peripheral tissues. In the light of all this information, nesfatin-1 may be considered to be an important regulator in the metabolic process. Nesfatin-1 appears to be able to contribute to the treatment of obesity and diabetes because of its anorexigenic and antihyperglycemic effects. Key teaching pointsNesfatin-1 is a anorexigenic peptide.Nesfatin-1 is derived from Nucleobindin-2.Nucleobindin-2 mRNA is produced in different areas of the brain.Nesfatin-1 is an inhibitory factor on appetite and a regulator of energy balance that reduces the increase in body weight.

Localisation of the radial nerve at the spiral groove: A new technique.

BACKGROUND: Localisation of the radial nerve (RN) in the spiral groove by previously reported methods has a wide range and is generalised. The objective of this study was to establish a method unique to a patient to accurately localise the nerve. METHODS: The distance between RN at the midpoint of the spiral groove (D) and the tip of the olecranon (O) was compared with the most distal wrist flexion crease and fingertips on 100 healthy volunteers. The RN was found by ultrasound examination. RESULTS: The mean distance from O to D was 16.22 cm (12.5-20.5 ± 1.55), and mean distances from wrist crease (WC) to second, third, fourth and fifth fingertips were 17.79 (14-20 ± 1.28), 18.66 (15-21 ± 1.32), 17.71 (14.5-20.5 ± 1.32) and 15.62 (12.5-20.5 ± 1.34) cm, respectively. With regards to O-D distance, the strongest relationship was obtained for the distance between the fifth fingertip to the WC (r = 0.708, p < 0.001). This relationship was stronger among females than males (p < 0.001). CONCLUSION: The course of the RN can be easily found at the upper arm by this method, which is unique to a patient. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study presents a new and individualised approach to accurately predict the location of the RN in the spiral groove. This method is clinically relevant and can be used to guide the surgical explorations or expedite interventional methods.

Characteristics of patients admitted to the emergency department due to tick bite.

Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease endemic in Turkey since 2002. Çorum is one of the leading five cities in Turkey in which CCHF disease is seen most. We studied characteristics of the patients with tick bites in our emergency department (ED) and determined the fatality rate of the disease in city of Çorum for the first time. We retrospectively analysed the characteristics of the patients admitted to our ED from the medical files of 21,680 patients in a 5-year period. The number of patients with definite diagnosis and who have died was determined. Our results demonstrated that the fatality rate of CCHF in Çorum is 6.78%. Among 21,680 patients, blood samples of 970 patients were sent to an advanced centre in Ankara for polymerase chain reaction (PCR) testing. Results of 560 patients were reported to be PCR (+) and 38 of them have died.

Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection.

BACKGROUND: Multiple embryo transfer during in vitro fertilisation (IVF) increases multiple pregnancy rates causing maternal and perinatal morbidity. Single embryo transfer is now being seriously considered as a means of minimising the risk of multiple pregnancy. However, this needs to be balanced against the risk of jeopardising the overall live birth rate. OBJECTIVES: To evaluate the effectiveness and safety of different policies for the number of embryos transferred in couples who undergo assisted reproductive technology (ART). SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, from inception to July 2013. We handsearched reference lists of articles, trial registers and relevant conference proceedings and contacted researchers in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different policies for the number of embryos transferred following IVF or intra-cytoplasmic sperm injection (ICSI) in subfertile women. Studies of fresh or frozen and thawed transfer of one, two, three or four embryos at cleavage or blastocyst stage were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The overall quality of the evidence was graded in a summary of findings table. MAIN RESULTS: Fourteen RCTs were included in the review (2165 women). Thirteen compared cleavage-stage transfers (2017 women) and two compared blastocyst transfers (148 women): one study compared both. No studies compared repeated multiple versus repeated single embryo transfer (SET). DET versus repeated SETDET was compared with repeated SET in three studies of cleavage-stage transfer. In these studies the SET group received either two cycles of fresh SET (one study) or one cycle of fresh SET followed by one frozen SET in a natural or hormone-stimulated cycle (two studies). When these three studies were pooled, the cumulative live birth rate after one cycle of DET was not significantly different from the rate after repeated SET (OR 1.22, 95% CI 0.92 to 1.62, three studies, n=811, I(2)=0%, low quality evidence). This suggests that for a woman with a 40% chance of live birth following a single cycle of DET, the chance following repeated SET would be between 30% and 42%. The multiple pregnancy rate was significantly higher in the DET group (OR 30.54, 95% CI 7.46 to 124.95, three RCTs, n = 811, I(2) = 23%, low quality evidence), suggesting that for a woman with a 15% risk of multiple pregnancy following a single cycle of DET, the risk following repeated SET would be between 0% and 2%. Single-cycle DET versus single-cycle SETA single cycle of DET was compared with a single cycle of SET in 10 studies, nine comparing cleavage-stage transfers and two comparing blastocyst-stage transfers. When all studies were pooled the live birth rate was significantly higher in the DET group (OR 2.07, 95% CI 1.68 to 2.57, nine studies, n = 1564, I(2) = 0%, high quality evidence). This suggests that for a woman with a 40% chance of live birth following a single cycle of DET, the chance following a single cycle of SET would be between 22% and 30%. The multiple pregnancy rate was also significantly higher in the DET group (OR 8.47, 95% CI 4.97 to 14.43, 10 studies, n = 1612, I(2) = 45%, high quality evidence), suggesting that for a woman with a 15% risk of multiple pregnancy following a single cycle of DET, the risk following a single cycle of SET would be between 1% and 4%. The heterogeneity for this analysis was attributable to a study with a high rate of cross-over between treatment arms. Other comparisons Other fresh cycle comparisons were evaluated in three studies which compared DET versus transfer of three or four embryos. Live birth rates did not differ significantly between the groups for any comparison, but there was a significantly lower multiple pregnancy rate in the DET group than in the three embryo transfer (TET) group (OR 0.36, 95% CI 0.13 to 0.99, two studies, n = 343, I(2) = 0%). AUTHORS' CONCLUSIONS: In a single fresh IVF cycle, single embryo transfer is associated with a lower live birth rate than double embryo transfer. However, there is no evidence of a significant difference in the cumulative live birth rate when a single cycle of double embryo transfer is compared with repeated SET (either two cycles of fresh SET or one cycle of fresh SET followed by one frozen SET in a natural or hormone-stimulated cycle). Single embryo transfer is associated with much lower rates of multiple pregnancy than other embryo transfer policies. A policy of repeated SET may minimise the risk of multiple pregnancy in couples undergoing ART without substantially reducing the likelihood of achieving a live birth. Most of the evidence currently available concerns younger women with a good prognosis.

Number of embryos for transfer following in-vitro fertilisation or intra-cytoplasmic sperm injection.

BACKGROUND: Multiple embryo transfer during IVF has increased multiple pregnancy rates (MPR) causing maternal and perinatal morbidity. Elective single embryo transfer (SET) is now being considered as an effective means of reducing this iatrogenic complication. OBJECTIVES: To determine in couples undergoing IVF/ICSI (intra-cytoplasmic sperm injection) whether:(1) elective transfer of two embryos improves the probability of livebirth compared with:(a) elective single embryo transfer,(b) three embryo transfer (TET) or(c) four embryo transfer (FET).(2) elective transfer of three embryos improves the probability of livebirth compared with:(a) elective single embryo transfer, or(b) elective four embryo transfer. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's trials register (searched March 2008), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 1, 2008), MEDLINE (1970 to 2008), EMBASE (1985 to 2008) and reference lists of articles. Relevant conference proceedings were hand-searched and researchers in the field contacted. SELECTION CRITERIA: Randomised controlled trials were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility and quality of trials. MAIN RESULTS: For the update in 2008 five trials compared DET with SET. DET versus TET and DET versus FET were evaluated in a single small trial each. The difference in cumulative livebirth rates (CLBR) after DET and those after SET followed by transfer of a single frozen thawed embryo (1FZET) was not statistically significant (OR 0.81, 95% CI 0.59 to 1.11; p=0.18). There was no statistically significant difference in CLBR after a single fresh cycle of DET versus two fresh cycles of SET (OR 1.23, 95% CI 0.56 to 2.69, p= 0.60 ). The live birth rate (LBR) per woman in a single fresh treatment was higher following DET than SET (OR 2.10, 95% CI 1.65 to 2.66, p<0.00001). The MPR was lower following SET (OR 0.04, 95% CI 0.01 to 0.11; p< 0.00001). The CLBR following two fresh cycles of DET versus two fresh cycles of TET (OR 0.77, 95%CI 0.22 to 2.65, p=0.67) and CLBR after three fresh cycles of DET versus three fresh cycles of TET showed no statistically significant differences (OR 0.77, 95% CI 0.24 to 2.52; p=0.67). There were no statistically significant differences between DET and TET in terms of LBR (OR 0.40, 95%CI 0.09 to 1.85; p=0.24) and MPR (OR 0.17, 95%CI 0.01 to 3.85; p= 0.27). DET led to lower LBR than FET but the difference was not statistically significant (OR 0.35, 95% CI 0.11 to 1.05; p = 0.06). AUTHORS' CONCLUSIONS: In a single fresh IVF cycle, SET is associated with a lower LBR than DET. However there is no significant difference in CLBR following SET+ 1FZET and the LBR following a single cycle of DET. MPR are lowered following SET compared with other transfer policies. There are insufficient data on the outcome of two versus three and four embryo transfer policies.

Response to controlled ovarian stimulation and oocyte quality in women with myotonic dystrophy type I.

PURPOSE: In women the relationship between myotonic dystrophy type I and fertility remains controversial. The objective of this study was to evaluate the ovarian reserve, ovarian response to stimulation and oocyte quality in these patients. MATERIALS AND METHODS: We compared 15 myotonic dystrophy type I patients with 39 age matched controls with isolated male factor infertility necessitating ICSI. RESULTS: All parameters of ovarian reserve (day 3 FSH and E2, antral follicle count and delta E2) were significantly better in the controls. Despite having significantly lower doses of gonadotrophin, the control group attained a higher number of retrieved oocyte-cumulus complexes (p < 0.04). Analysis of cytoplasmic and extracytoplasmic dysmorphism did not reveal any difference between the two groups. Fertilisation rate and top grade embryos on day 3 were similar in both groups. CONCLUSION: The present study suggests that though women with myotonic dystrophy type I have a reduced ovarian reserve and respond poorly to controlled ovarian stimulation, there is no impact on oocyte and embryo quality. Hence suggesting that successful ART is feasible with appropriate selection in women with mild myotonic dystrophy.

Comparison of oocyte quality and intracytoplasmic sperm injection outcome in women with isolated polycystic ovaries or polycystic ovarian syndrome.

OBJECTIVE: To compare the oocyte quality and intracytoplasmic sperm injection performance in women with isolated polycystic ovaries or polycystic ovarian syndrome. DESIGN: Retrospective study. SETTING: Fertility unit. POPULATION: Three study groups were identified: women with PCO-only morphology (50 cycles), PCOS (51 cycles) and age matched control group (104 cycles) with isolated male factor infertility necessitating ICSI. METHOD: Controlled ovarian hyperstimulation and ICSI. MAIN OUTCOME MEASURES: Response to gonadotropin stimulation, oocyte and embryo quality, clinical pregnancy rate and pregnancy outcome. RESULTS: Despite a significantly lower total gonadotropin dose, a significantly higher serum E2 level was attained in both the PCOS and the PCO-only groups compared to the control group. Although significantly more oocytes were retrieved in the PCOS and PCO-only groups, the number of 2-pronuclear embryos was similar to controls. No significant differences were noted in the maturity of the oocytes, oocyte dysmorphism, embryo quality, implantation and pregnancy rates among the three groups. However the clinical miscarriage rate was significantly lower in women with PCO-only morphology group (15.4 versus 31%, P < 0.05) than in the PCOS group. CONCLUSION: Women with PCO-only appearance have shown to have similar characteristics to women with PCOS in terms of ovarian response to hMG stimulation, oocyte and embryo quality and pregnancy rates. However miscarriage rates were significantly lower in the PCO-only group than the PCOS group. Our findings suggest that factors unrelated to oocyte and embryo morphology present in PCOS patients may be instrumental in adverse reproductive outcomes in these women.

Mifepristone vaginally in an early medical abortion regimen: a pilot study.

OBJECTIVE: This prospective observational pilot study was undertaken to assess the efficacy of mifepristone and misoprostol, both administered vaginally. The ultimate goal is to investigate alternative means of reducing the time interval between the two treatments involved. The efficacy of the early medical abortion regimen utilizing mifepristone and misoprostol is beyond doubt. The regimen usually involves administering misoprostol 36 h following oral administration of mifepristone. The interval between the two treatment components might affect a woman's choice of the medical method. METHODS: Eighteen women undergoing abortion for nonmedical reasons were recruited. RESULTS: Seven women required further intervention to achieve complete abortion. Median induction-to-abortion interval was 7.66 h in the 11 women with complete abortion. CONCLUSION: The complete abortion rate of 61% in this study was lower than that with the standard medical regimen.

Drug intervention in early pregnancy after assisted reproductive technology.

Implantation in humans is a complex, closely regulated, highly selective and relatively poorly understood process. Humans have the highest rate of miscarriage in mammals and various pharmacological manipulations have been used to minimize pregnancy losses in both spontaneous pregnancies and pregnancies resulting from assisted reproduction technology. The widespread application of protocols using numerous drugs in assisted reproduction treatment has led to an increasing number of pregnancies exposed to these drugs. The vast majority of these protocols have been based on data from a few observational and often retrospective clinical studies. This paper reviews the recent literature on drug interventions in early pregnancy after assisted reproduction treatment. It is concluded that there are still numerous issues about the safety of most drugs for both the women and their fetus. In many cases, the benefits are theoretical and the possible long-term side-effects are untested. There is an urgent need for more epidemiological studies and randomized controlled trials to explore the use, efficacy and side-effects of both old and new drugs in early pregnancy after assisted reproduction treatment.

Role of utero-ovarian vascular impedance: predictor of ongoing pregnancy in an IVF-embryo transfer programme.

The objective of this study was to evaluate the role of uterine, endometrial and follicular blood flow in prediction of ongoing pregnancy after assisted conception. A prospective observational study was conducted on 53 women undergoing IVF treatment. Transvaginal colour and pulsed Doppler measurements were performed on the day that pituitary suppression was confirmed, on day 10 of ovarian stimulation and on the day prior to human chorionic gonadotrophin injection. On the last day of ovarian stimulation, blood flow in the ascending uterine artery of the women who would conceive was characterized by significantly lower pulsatility index values. Sub-endometrial vascular impedance was comparable in the pregnant and non-pregnant groups. There were no differences in the perifollicular vascularity between pregnant and non-pregnant women. The chance of achieving pregnancy predicted by uterine artery Doppler and perifollicular blood flow in women whose PI values were higher than 3.26 and 1.08 was very low, with a sensitivity of 1.00 and specificity of 0.59 and 0.82 respectively. The data provide evidence for an association between utero-ovarian perfusion and reproductive outcome following IVF treatment. Uterine and ovarian vascular impedance values identify those women whose pregnancy chances are significantly limited. Measures to decrease vascular impedance in such women might enhance pregnancy rates by improving embryo quality and uterine receptivity for implantation.

In-vitro fertilisation and risk of multiple pregnancy.

There is concern about the medical, social, and economic consequences of multiple pregnancy after in-vitro fertilisation (IVF). The most effective way to limit the risk of such a pregnancy is to replace only one or two embryos simultaneously. This strategy, however, is thought to reduce pregnancy rates. We analysed the rates of multiple pregnancies and live-births in all clinics in the UK in relation to their elective two-embryo transfer (ETT) policies. Our results suggest that replacement of two embryos eliminates the chance of triplets without affecting overall success rates.