Outcomes of BRCA pre-implantation genetic testing according to the parental mutation origin: a cohort study.

BACKGROUND: The process of gamete formation and early embryonic development involves rapid DNA replication, chromosome segregation and cell division. These processes may be affected by mutations in the BRCA1/2 genes. The aim of this study was to evaluate BRCA mutation inheritance and its effect on early embryonic development according to the parental origin of the mutation. The study question was approached by analyzing in vitro fertilization cycles (IVF) that included pre-implantation testing (PGT-M) for a BRCA gene mutation. METHODS: This retrospective cohort study compared cycles of pre-implantation genetic testing for mutations (PGT-M) between male and female patients diagnosed with BRCA 1/2 mutations (cases), to a control group of two other mutations with dominant inheritance (myotonic dystrophy (MD) and polycystic kidney disease (PKD)). Results were compared according to mutation type and through a generalized linear model analysis. RESULTS: The cohort included 88 PGT-M cycles (47 BRCA and 41 non-BRCA) among 50 patients. Maternal and paternal ages at oocyte retrieval were comparable between groups. When tested per cycle, FSH dose, maximum estradiol level, oocytes retrieved, number of zygotes, and number of embryos available for biopsy and affected embryos, were not significantly different among mutation types. All together 444 embryos were biopsied: the rate of affected embryos was comparable between groups. Among BRCA patients, the proportion of affected embryos was similar between maternal and paternal mutation origin (p = 0.24). In a generalized linear model analysis, the relative oocyte yield in maternal BRCA patients was significantly lower (0.7, as related to the non BRCA group)(p < 0.001). Zygote formation and blastulation were not affected by the BRCA gene among paternal cases (P = 0.176 and P = 0.293 respectively), nor by paternal versus maternal BRCA carriage (P = 0.904 and P = 0.149, respectively). CONCLUSIONS: BRCA PGT-M cycles performed similarly compared to non-BRCA cycles. Inheritance rate and cycle parameters were not affected by the parental origin of the mutation.

Fertility preservation for women with ovarian endometriosis: results from a retrospective cohort study.

RESEARCH QUESTION: What is the outcome of fertility-preservation treatments in women with endometrioma, especially those with endometrioma larger than 4 cm? DESIGN: Retrospective cohort study. Women with definitive diagnosis of ovarian endometriosis (by histology or ultrasound), who underwent fertility-preservation treatment in two IVF units between 2016 and 2021, were included. As some women cryopreserved oocytes and other embryos, the primary outcome was the number of metaphase II (MII) oocytes retrieved. RESULTS: Seventy-one women with ovarian endometriosis (OMA) underwent 138 fertility-preservation cycles. The median age of patients was 31 years. Forty out of 71 (56%) women underwent at least one surgery for OMA before fertility-preservation treatment. Multivariate analysis of each patient's first cycle was used. Women who underwent OMA surgery before fertility-preservation treatment had a 51.7% reduction (95% CI 26.1 to 68.5, P = 0.001) in the number of MII oocytes compared with women with OMA who did not undergo surgery. Among a subgroup who did not undergo surgery, those with an endometrioma larger than 4 cm had similar anti-Müllerian hormone concentration (2.6 ng/ml versus 2.1 ng/ml), number of oocytes retrieved (9 versus 9) and number of MII oocytes (7.6 versus seven 7) compared with women with an endometrioma of 4 cm or less. CONCLUSIONS: Discussing fertility-preservation treatment options with patients with OMA is recommended, especially if surgery is planned.

You are not in the army now! A field study on the impact of a Preparation for Civilian Life program on young soldiers.

Recent years have seen the implementation of educational programs aimed at developing future orientation and better employability skills, mostly for people new to or returning to the job market. In a field study, we investigated the impact of a 5-day program on reintegration to civilian life on young Israeli combat soldiers' time preferences, gratitude, patriotism, and perceptions of their combat experience. Questionnaires administered before and after the program revealed a positive effect on future orientation but a negative effect on gratitude and perceptions of the combat experience. Although the positive effect on future orientation is in line with the program design, the negative effects found should be taken into consideration when planning or improving similar educational programs.

The effects of the COVID-19 crisis on the subjective well-being of the Israeli population-monitored phase by phase.

The paper examined the effect of the pandemic outbreak of COVID-19 on the cognitive and affective components of subjective well-being (SWB) over time in Israel. Just before the first verified patient, we ran a survey of the general population that included questions concerning both components of SWB, self-rated health, income satisfaction, and other socio-demographic aspects. The same survey among different respondents from the same population during the lockdown period when no exit strategy had been conveyed, and for the third time when the exit strategy was publicized and began to be implemented. The findings show that the cognitive component of SWB, as measured by Cantril's Ladder, remained stable over the long term. The average respondent reported unchanged life evaluation even when the individual's negative feelings rose by 52%, and positive feelings fell by 16%. We show evidence for a structural change in the weighting of feelings and self-rated health in life satisfaction function.

Fresh transfer of Day 5 slow-growing embryos versus deferred transfer of vitrified, fully expanded Day 6 blastocysts: which is the optimal approach?

STUDY QUESTION: In IVF cycles in which the entire embryo cohort is slow growing, is it optimal to perform fresh transfer in Day 5 or to extend the culture and transfer in subsequent vitrified-warmed cycles? SUMMARY ANSWER: The outcomes depend on the degree of embryo development on Day 5. WHAT IS KNOWN ALREADY: Slow-growing blastocysts have lower implantation potential when transferred in fresh cycles. It has been suggested that embryo-endometrial asynchrony could explain this finding. However, studies that compared Days 5 and 6 embryos in frozen embryo transfer (FET) cycles showed contradictory results. There is still a lack of evidence regarding the best approach, performing fresh transfer or deferring transfer and continuing culture until fully developed blastocysts are achieved, when the entire cohort of embryos is slow growing. STUDY DESIGN SIZE, DURATION: This was a retrospective study that included 477 women aged <40 years who underwent fresh Day 5 single embryo transfer of slow-growing embryos and subsequent FET cycles of fully expanded blastocysts (FEB) originating from the same IVF cycle between 2012 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included cycles in which the embryos either began blastulation by Day 5 of culture but did not reach the fully expanded stage (Gardner Stage III) or had delayed blastulation with only morula embryos present by Day 5 of culture. All of the subjects in the study underwent elective, single embryo transfer (slow or delayed blastocysts) on Day 5 and had at least one embryo that developed into a FEB on extended culture Day 6 that was suitable for vitrification. All subjects, regardless of the outcome of the fresh transfer, returned for at least one subsequent FET cycle of Day 6 embryos. MAIN RESULTS AND ROLE OF CHANCE: A total of 1070 embryo transfer cycles (fresh + FET) were included. Of them, 365 women had elective, fresh, single transfer of slow-growing blastocysts (Group I) and 112 had elective, fresh, single morula transfer (Group II). Groups I and II underwent a subsequent 457 and 136 FET cycles, respectively. The mean age of Group I was 33.8 ± 2.9 years, the proportion of Day 5 embryos that developed to FEB by Day 6 was 92%, and the number of blastocysts vitrified was 627 (average of 1.71 blastocysts per cycle). The outcomes of fresh and FET cycles were comparable regarding clinical pregnancy rate (CPR) (31.0 vs. 30.4%, P = 0.86) and live birth rate (LBR) (23.3 vs. 20.3%, P = 0.15). In Group II, the mean age was 35.8 ± 3.4 years and the proportion of morula embryos that developed to FEB by Day 6 was 72%. The number of blastocysts vitrified on Day 6 was 155 (1.38 per cycle). The transfer of fresh embryos in Group II resulted in significantly lower clinical pregnancy (5.3 vs. 30.1%, P < 0.001) and LBRs (1.8 vs. 20.5%, P < 0.001). The results did not change after controlling for possible confounding factors. LIMITATIONS AND REASONS FOR CAUTION: The retrospective design of the study is a major limitation. Although we compared the outcomes of embryos that originated from the same cohort, the FET cycles could have been overrepresented by older patients and those with poorer prognoses. Furthermore, the study included only cycles in which there were blastocysts available for cryopreservation on Day 6; therefore, the results were not be applicable for those who had mandatory Day 5 transfer with no embryos available for vitrification. WIDER IMPLICATIONS OF THE FINDINGS: Fresh transfer of embryos that begin blastulation on Day 5 results in similar outcomes to the transfer of FEB originating from the same cohort. However, in cases where only morula/compacting embryos are available by Day 5, extending culture until FEB are achieved and then performing subsequent FET will result in significantly higher LBRs. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Repeated GnRH agonist doses for luteal support: a proof of concept.

RESEARCH QUESTION: What are the safety and feasibility of repeated subcutaneous doses of gonadotrophin-releasing hormone (GnRH) agonist for luteal support in IVF cycles triggered by a GnRH agonist? DESIGN: In this prospective trial, patients exhibiting oestradiol concentrations of over 2500 pg/ml after use of a GnRH agonist for triggering ovulation were initially randomized to GnRH agonist luteal support (0.1 mg subcutaneously every other day, starting on day 3 after embryo transfer) or to a control group supported by 80 µg of recombinant human chorionic gonadotrophin (HCG) on day 3 after embryo transfer. All patients underwent a day 5 blastocyst transfer. Randomization to the HCG luteal support was stopped owing to two cases of ovarian hyperstimulation syndrome (OHSS) and the study was continued solely with GnRH agonist luteal support. RESULTS: The study included 39 women in the repeated GnRH agonist luteal support group and seven in the HCG micro dose group. There were no cases of OHSS among patients supported by a GnRH agonist, and no other adverse events were recorded. There were no cases of bleeding before the pregnancy test, and hence no cases of an insufficient luteal phase. A clinical pregnancy rate of 43.6% was achieved with GnRH agonist luteal support. Hormone dynamics during the stimulation cycle reflected rising LH and progesterone concentrations after the introduction of GnRH agonist support. CONCLUSIONS: Repeated doses of GnRH agonist every other day as a method of luteal support provided safe and effective luteal support for women who underwent GnRH agonist triggering in a GnRH antagonist IVF cycle.

Does stress affect IVF outcomes? A prospective study of physiological and psychological stress in women undergoing IVF.

RESEARCH QUESTION: What are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF? DESIGN: A prospective cohort study of 72 patients undergoing IVF in 2017 and 2018. Physiological stress was assessed by salivary cortisol measurements: (i) pretreatment, when the patient received the IVF protocol; (ii) before oocyte retrieval (follicular cortisol was also measured); and (iii) before embryo transfer. Emotional stress was evaluated at each assessment with the State-Trait Anxiety Inventory and a 1-10 Visual Analogue Scale (VAS, referred to as the 'Stress Scale'. Correlations between cortisol concentrations, psychological stress and IVF outcome were assessed. RESULTS: Salivary cortisol concentrations increased by 28% from pretreatment phase (0.46 ± 0.28 µg/dl) to maximum concentration on oocyte retrieval day (0.59 ± 0.29 µg/dl, P = 0.029) and then decreased by 29% on embryo transfer day (0.42 ± 0.23 µg/dl, P = 0.0162). On embryo transfer day, cortisol among women in their first cycle was higher than women who underwent more than one treatment (P = 0.024). Stress Scale score increased by 39% from pretreatment to a maximum score on oocyte retrieval day and then decreased by 12% on embryo transfer day. Salivary cortisol and Stress Scale were not related to subsequent embryo transfer, fertilization rate, embryo quality or clinical pregnancy rate. Follicular cortisol concentration was positively correlated with fertilization rate (r = 0.4, P = 0.004). CONCLUSION: It can be cautiously concluded that physiological and psychological stress do not negatively affect IVF outcomes. Moreover, high follicular cortisol concentrations might have positive effects on pregnancy rates.

The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age.

STUDY QUESTION: Does ICSI improve reproductive outcomes compared with conventional IVF when used for non-male factor infertility in women aged 40 years and over? SUMMARY ANSWER: There is no advantage of ICSI over conventional IVF in women aged 40 years and over when used for non-male factor infertility. WHAT IS KNOWN ALREADY: The use of ICSI has increased dramatically in recent years and is being applied for indications other than male factor infertility. Currently, ICSI is used in 65% of IVF cycles in Europe and in 76% of cycles in the USA. Despite its increase use, there is no clear evidence of a benefit in using ICSI over conventional IVF. Older women undergoing infertility treatments are at an increased risk of having diminished ovarian reserve and lower oocyte quality, which could make ICSI the preferred insemination method in this group. However, studies that have examined the benefits of ICSI in this age group are lacking. STUDY DESIGN, SIZE, DURATION: A retrospective, single center study included women, aged 40-43 years, who underwent IVF treatments for non-male factor infertility between January 2012 until June 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 745 women were included in the study. Of these, 490 women underwent ICSI and 255 women underwent conventional IVF. In order to be included in the study, women had to be at least 40 years of age at the beginning of ovarian stimulation and their male partner had to have normal sperm parameters according to World Health Organisation (WHO) fifth edition. Exclusion criteria included: more than three previous IVF cycles, a history of fertilization failure or low fertilization (<50%), the use of donor or frozen oocytes and the use of donor or frozen sperm samples. The primary outcome was the live birth rate. Secondary outcomes included fertilization rates, fertilization failure and embryo quality. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were similar between the two groups, except for the number of previous IVF cycles, which was higher in the ICSI group (1.0 vs. 0.6, P = 0.0001). Despite similar numbers of oocytes retrieved (7.2 vs. 6.5), when examining oocytes maturity (performed 2 h after oocyte retrieval in the ICSI group and after 18 h in the conventional IVF group), the conventional IVF group had a higher number of Metaphase II (MII) oocytes (6.1 vs. 4.7, P < 0.0001). The conventional IVF group also had higher numbers of zygotes formed (4.48 vs. 3.66, P = 0.001), more cycles with embryos transferred at the blastocyst stage (36 vs. 26%, P = 0.005) and more cycles where embryos were available for cryopreservation (26.4 vs. 19.7%, P = 0.048), compared with the ICSI group. The fertilization rates (64 vs. 67%) and fertilization failure (9.0 vs. 9.7%) were similar. After logistic regression analysis controlling for confounders, the live birth rates were similar between the groups (11.9 vs. 9.6%). Subgroup analyses of women undergoing their first IVF cycle and women with ≤3 oocytes retrieved did not show an advantage of ICSI over conventional IVF. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of this study was a major limitation. The ICSI group had a higher number of previous IVF cycles, which could mean that ICSI was performed in poorer prognosis patients. Moreover, although this study is one of the largest studies to examine the question of whether ICSI is of value for older women with non-male factor infertility, based on a post hoc power analysis, it was still underpowered to detect differences in live birth rates, which can limit the conclusions of the study. Prospective studies are needed to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: The decision regarding performing ICSI should be based on sperm parameters and previous history. The use of ICSI for the sole indication of advanced maternal age shows no benefit over conventional IVF. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Vitrified-warmed single-embryo transfers may be associated with increased maternal complications compared with fresh single-embryo transfers.

Cryopreservation of embryos allows single-embryo transfer and storage of supernumerary embryos, maximizing cumulative pregnancy rates. The purpose of this retrospective cohort study was to compare pregnancy outcome in singletons born after fresh or vitrified-warmed single blastocyst transfer (SBT). Singleton live births resulting from SBT of fresh or vitrified-warmed embryos were compared. Primary outcomes were perinatal outcomes including small for gestational age (SGA), low birthweight, preterm deliveries (PTD), large for gestational age (LGA) and congenital malformations. Maternal complications included pre-eclampsia, placenta previa, placental abruption, gestational diabetes mellitus (GDM) and chorioamnionitis. Adjustment for confounding factors was performed. Of 1886 fresh SBTs and 1200 vitrified-warmed SBTs during the study period, vitrified-warmed SBTs compared with fresh SBTs resulted in significantly lower clinical pregnancy rate (P < 0.0001). Live birth and miscarriage rates calculated only for pregnancy with known outcome revealed lower live birth rates and higher miscarriage rates for the vitrified-warmed group. Perinatal complications were calculated for clinical pregnancies with known outcomes (12.9% catchment failure was excluded from analysis). The vitrified-warmed group showed a trend toward higher rates of pre-eclampsia, GDM, Caesarean delivery and LGA neonates. Rates of PTD and SGA were comparable. In conclusion, vitrified-warmed SBT might be associated with increased feto-maternal complications.

Cumulative live birth rate following elective single blastocyst transfer compared with double blastocyst transfer in women aged 40 years and over.

This retrospective cohort study aimed to identify predictive factors for live birth following blastocyst transfer in women aged 40-43, and to compare the cumulative live birth rate (LBR) following elective single blastocyst (eSBT) and double blastocyst (DBT) transfer. The study included 411 women who had fresh blastocyst transfers on day 5. In stepwise logistic regression, independent predictive factors for live birth were: transferring fully expanded blastocysts (Gardner stage ≥3) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.59-9.71) and transferring two blastocysts compared with a single blastocyst (OR 1.7, 95% CI 1.08-2.9). Maternal age was not found to be significant (OR 0.78, 95% CI 0.62-1.1). When comparing eSBT (n = 150) with DBT (n = 151), the DBT group achieved higher LBRs (26.5 versus 19.3%, P = 0.017) and higher multiple births (0 versus 17.5%, P = 0.02). However, the cumulative LBR was similar (28.0 versus 31.1%), with significantly lower multiple births in the eSBT group (0 versus 14.9%, P = 0.03). These results indicate that in women aged 40-43, when fully expanded blastocysts are achieved, maternal age is not a predictor for live birth, and eSBT can be performed without compromising cumulative LBRs.

Predictive value of serum HCG concentrations in pregnancies achieved after single fresh or vitrified-warmed blastocyst transfer.

Possible differences between serum HCG levels in pregnancies achieved after transfer of a single fresh or a vitrified-warmed blastocyst were evaluated. Out of 1130 single blastocyst transfers resulting in positive HCG results, 789 were single fresh blastocyst transfers and 341 single vitrified-warmed blastocyst transfers. The initial serum HCG levels of 869 clinical intrauterine pregnancies were evaluated, 638 after the transfer of a single fresh blastocysts and 231 after the transfer of a single vitrified-warmed blastocysts. The HCG levels from cycles resulting in a clinical intrauterine pregnancy were significantly higher after the transfer of a single vitrified-warmed blastocyst (383 ± 230 IU/l) versus a fresh transfer (334 ± 192 IU/l; P = 0.01). Threshold values for predicting a clinical pregnancy for a fresh blastocyst were 111 IU/l and for a vitrified-warmed blastocyst 137 IU/l. Our study shows that the overall beta-HCG levels are comparable after the transfer of a fresh or vitrified-warmed blastocyst, suggesting that vitrification most probably does not affect the ability of the embryos to produce beta-HCG. This study further shows that when clinicians counsel patients, they should take into account that higher HCG levels are needed after a vitrified-warmed blastocyst transfer to predict a clinical intrauterine pregnancy.

Obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic diagnosis: cohort study and meta-analysis.

Preimplantation genetic diagnosis (PGD) may pose risks to pregnancy outcome owing to the invasiveness of the biopsy procedure. This study compares outcome of singleton and twin clinical pregnancies conceived after fresh embryo transfers of PGD (n = 89) and matched intracytoplasmic sperm injection (ICSI) pregnancies (n = 166). The study was carried out in a single university affiliated centre. Because of the paucity of available data, a literature-based meta-analysis of studies comparing neonatal outcome of PGD and ICSI pregnancies was also conducted. In the retrospective cohort study, obstetric and neonatal outcome were available in 67 PGD and 118 ICSI pregnancies. Perinatal outcomes were comparable between PGD and ICSI pregnancies. Meta-analysis revealed similar outcomes, except for higher rate of low birth weight (<2500 g) neonates in ICSI twin pregnancies (RR 0.86, 95% CI 0.74 to 1.0). Mean birth weight, gestational age at birth, pre-term deliveries (<37 weeks) and malformations were all comparable. In this cohort study and subsequent meta-analysis, no association was found between PGD conceived pregnancies and risks of adverse neonatal or obstetrical outcomes compared with ICSI pregnancies. Hence, blastomere biopsy for PGD does not seem to increase the risk for adverse perinatal outcome compared with ICSI pregnancies.

Can we alter pregnancy outcome by adjusting progesterone treatment at mid-luteal phase: a randomized controlled trial.

Our study aimed to determine whether mid-luteal serum P concentrations can serve as a predictive factor for in vitro fertilization (IVF) outcomes and whether increasing P dosage for patients with low levels at mid-luteal phase may improve pregnancy rates. It was a prospective, randomized controlled study. A total of 146 patients undergoing IVF treatment were prospectively enrolled and received routine luteal phase support (LPS) regimen of Endometrin® (progesterone) 200 mg/day. Serum P levels were measured 7 days after embryo transfer (ET). Considering a cutoff level of 15 ng/ml on this day, patients with higher levels continued the same dosage until pregnancy test (control group). Patients with lower levels were randomly allocated to continue Endometrin® 200 mg/day (Group A) or to increase Endometrin® dosage to 300 mg/day (Group B). The Main Outcome Measures were pregnancy rates. Both biochemical and clinical pregnancy and live birth rates were comparable between all groups regardless of P level on day 7 of luteal phase and regardless of dose adjustment. ROC analysis determined that mid-luteal P levels of 17 ng/ml can be a better predictor of cycle outcome. In conclusion raising the P dose at mid-luteal phase to 300 mg daily did not improve cycle outcomes.

Comparison between stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF with GnRH antagonist protocol.

PURPOSE: Highly purified Human Menopausal Gonadotropins (hp-hMG) and recombinant FSH (rFSH) are widely used in assisted reproductive technology (ART). The aim of this study was to compare ART results of the two preparations in GnRH antagonist cycles. METHODS: In this retrospective cohort study, IVF antagonist cycles performed from 2011 through 2013 were reviewed. There were 508 antagonist cycles: 320 stimulated with rFSH and 188 with hp-hMG. For every hp-hMG, two rFSH were matched for patient's age and infertility diagnosis. Subgroup analysis of patients younger and older than 35 was done as well. RESULTS: Both treatments were resulted in comparable pregnancy and live birth rates. However, cumulative pregnancy rates were higher for the rFSH group. In the matching analysis, the rFSH group had more mature oocytes and more embryos while using lower doses of gonadotropins. Pregnancy, cumulative pregnancy rates, and live birth rates were comparable. In the subgroup analysis, young patients in the rFSH group had better cycle outcomes compared with those in the hp-hMG group. CONCLUSION: In antagonist protocol, different gonadotropin products are equally effective. The choice of one or the other should depend on the availability, convenience of use, and cost.

Can intra cytoplasmatic morphologically selected sperm injection (IMSI) technique improve outcome in patients with repeated IVF-ICSI failure? a comparative study.

OBJECTIVE: Spermatozoal morphology was reported to effect fertilization, embryo quality and pregnancy results in spontaneous conception and ART. Intracytoplasmic morphologically selected sperm injection (IMSI) is an innovative, not invasive technique, which examines the sperm with no harm at a magnification of 6000 × in order to obtain optimal sperm to perform IVF-ICSI. We evaluated the efficiency of IMSI technique in patients with repeated IVF-ICSI failure of at least three cycles with no viable pregnancy and/or very poor sperm quality. STUDY DESIGN AND METHODS: All couples who performed IMSI between the years 2009 to 2012 were enrolled retrospectively to the study. Couples with male infertility who were treated with IMSI were included in the study. All their treatments were evaluated and divided into two subgroups: conventional IVF-ICSI treatment and their subsequent IMSI treatment. Demographic data, clinical parameters and outcome were recorded. The IMSI treatments were compared to previous non-IMSI treatments in terms of fertilization rates, cleavage rates, number of embryos and their quality, number of embryos transferred and pregnancy outcome. MAIN RESULTS: Forty-two couples were reviewed. Basic characteristics of the groups were comparable. Fertilization and cleavage rates of the two groups were comparable. The embryos quality demonstrated a trend toward superior quality (grade 1-2) embryos in the IMSI versus ICSI (60% versus 47%; p = 0.07 and 53% versus 40%; p = 0.07), respectively. Implantation and clinical pregnancy rates were significantly superior in IMSI group (19.2% versus 7.8%; p = 0.042 and 41.3% versus 10.5%; p = 0.02, respectively). Miscarriage rate was significantly higher in conventional IVF-ICSI group (100% versus 15.8%; p = 0.04), and live birth rate was significantly higher in IMSI group (0 in conventional IVF-ICSI and 34.7% per transfer in IMSI group; p = 0.003). CONCLUSION: IVF outcome of IMSI resulted in a higher implantation rate, pregnancy rate and most importantly delivery rate compare to non IMSI treated cycles.

Unusual case of recurrent heterotopic pregnancy after bilateral salpingectomy and literature review.

Heterotopic pregnancy occurs in up to 1% of pregnancies after IVF and embryo transfer. A case of a 35-year-old woman undergoing IVF treatment who had had previous laparoscopic bilateral salpingectomy due to hydrosalpinges is presented. She had had two heterotopic pregnancies in both tubal stumps in consecutive pregnancies achieved by IVF. The intrauterine pregnancies ended in spontaneous abortions. The possibility of a heterotopic pregnancy needs to be considered when more than one embryo has been transferred in a cycle, especially when an inappropriately high serum ß-human chorionic gonadotrophin concentration is associated with an ultrasound finding of singleton intrauterine pregnancy.

Clinical pregnancy rates among anovulatory and oligoovulatory women after letrozole versus hormone replacement therapy in frozen-thawed embryo transfer cycles.

This cohort study investigated whether letrozole versus hormone replacement therapy (HRT) results in higher live birth rate among anovulatory and oligoovulatory women in frozen-thawed embryo transfer (FET) cycles. It was conducted from 1st February 2018 to 31st January 2019 and included 261 anovulatory and oligoovulatory women. Since letrozole has become an effective alternative to HRT cycles, 121 patients received letrozole in 121 cycles from 1st February 2018 to 31st January 2019 and were compared to 140 HRT FET cycles among 140 women from 1st February 2017 to 31st January 2018. The primary outcome was live birth rate. Secondary outcomes were clinical pregnancy, multiple pregnancy and miscarriage rates. Clinical pregnancy and live birth rates of transferred cleavage embryos were higher in the letrozole compared to the HRT group (36/65 (55.3%) vs. 20/110 (18.1%), p < 0.001) and (25/65 (38.4%) vs. 17/110 (15.4%), p < 0.001) respectively, whilst these rates were similar for transferred blastocyst embryos. Miscarriage and multiple pregnancy rates were similar between groups. The letrozole group was older than the HRT group (31.8 ± 5.1 vs. 29.9 ± 5.1 years, p = 0.002) and more smoked cigarettes (p = 0.035). Groups were similar regarding BMI, male versus non-male indication for fertility treatment, peak oestradiol levels, and numbers of oocytes retrieved, blastocysts, frozen and transferred embryos. Letrozole compared to HRT might improve live birth and clinical pregnancy rates among anovulatory and oligoovulatory women undergoing FET cycles.

Proangiogenic immature myeloid cells populate the human placenta and their presence correlates with placental and birthweight.

OBJECTIVE: To determine whether proangiogenic immature myeloid cells are present in human placentas. STUDY DESIGN: Biopsies were obtained from 61 placentas of term pregnancies. Percentage of CD45(+)CD33(+)LIN2(-)HLADR(-) immature myeloid cells of total CD45(+) hematopoietic cells was determined by flow cytometry. Location of immature myeloid cells in the placenta was identified using confocal microscopy. The proangiogenic potential of immature myeloid cells was analyzed by endothelial tube formation. RESULTS: Immature myeloid cells comprise ∼25% of human placental CD45(+) hematopoietic cells and infiltrate placentas in proximity of blood vessels. The percentage of immature myeloid cells correlated positively with placental weight (r(2) = 0.108, P = .01) and birthweight (r(2) = 0.087, P = .02). Endothelial tube formation was increased in the presence of immature myeloid cells as compared with the presence of CD45(+)LIN2(+) control cells. CONCLUSION: Human placentas are populated by immature myeloid cells in the proximity of blood vessels. Consistent with their involvement in angiogenesis, immature myeloid cells accelerated endothelial tube formation. The presence of immature myeloid cells in pathologic pregnancies warrants further studies.

Monitoring stimulated cycles during in vitro fertilization treatment with ultrasound only--preliminary results.

OBJECTIVE: To evaluate if monitoring patients by ultrasound (US) only during in vitro fertilization (IVF) treatment is safe. DESIGN: Randomized prospective study. INTERVENTION: Patients undergoing their first IVF treatment were randomized into two groups. The ultrasound only group (study group) was monitored by US for follicle size and endometrial thickness without blood tests. In this group, only one blood test was taken before human chorionic gonadotropin (hCG) injection, to ensure a safe level of estradiol (E(2)) regarding ovarian hyperstimulation syndrome (OHSS) risk. The control group was monitored by ultrasound plus serum estradiol and progesterone concentration at each visit. MAIN OUTCOME MEASURE: Clinical pregnancy rate. RESULTS: No differences were found between the groups in the parameters of IVF treatment, induction days, number of ampoules, E(2) level of hCG, as well as embryo quality. The clinical pregnancy rate was not statistically different between the groups, 57.5% vs. 40.0%, respectively (p = 0.25). No OHSS cases were found among the study or control groups. CONCLUSION: Ultrasound as a single monitoring tool for IVF cycles is reliable, safe, patient friendly, and reduces treatment expenses. In an era of cost effectiveness awareness, this regimen should be considered for routine management in IVF programs.