Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis?

RESEARCH QUESTION: Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? DESIGN: A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1-2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. RESULTS: The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 â€¯×  106/ml, with only a single participant (1.3%) with a sperm count of 12.5 â€¯×  106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. CONCLUSIONS: The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

Predicting IVF outcome in poor ovarian responders.

BACKGROUND: Poor responders to ovarian stimulation are one of the most challenging populations to treat. As a failed cycle can cause a considerable emotional and economical loss, adequate fertility counseling addressing patients' expectations are highly important when facing patients with poor ovarian response. The study aimed to evaluate reproductive outcomes and to identify factors associated with live birth (LB) after fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles of patients fulfilling the Bologna criteria for poor ovarian response (POR). METHODS: A retrospective study included 751 IVF/ICSI treatment cycles which yielded up to three retrieved oocytes, at a tertiary referral hospital between January 2016 and February 2020. A logistic regression analysis was used to adjust for confounders. RESULTS: Clinical pregnancy and LB rate per cycle were significantly higher among women younger versus older than 40 years (9.8% and 6.8% vs 4.5% and 2.1%, p < 0.01, respectively). Patients who achieved LB were significantly younger, had higher number of oocytes retrieved, fertilization rate and top-quality embryos (p < 0.05). Multivariable regression analysis identified patient's age (OR 0.90; 95% CI 0.845-0.97; p = 0.005) and mean number retrieved oocytes (OR 1.95; 95% CI 1.20-3.16; p = 0.007) as factors significantly associated with the probability of a LB. CONCLUSIONS: The woman's age and the number of retrieved oocytes are both independent predicting factors of live birth in poor ovarian responders. Considering the risks, the high financial investment and poor reproductive outcomes involved in IVF treatments, raises questions regarding the adequacy of providing treatments in these patients' population. POR younger than 40 years may represent a possible exception due to acceptable probability for a LB.

The association between level of physical activity and pregnancy rate after embryo transfer: a prospective study.

RESEARCH QUESTION: Is physical activity after embryo transfer, as assessed by a smart band activity tracker, associated with decreased pregnancy rates? DESIGN: Prospective observational cohort study comprising infertile women aged < 38 years, who had undergone fewer than three previous embryo transfers, achieved a good ovarian response and were undergoing frozen-thawed embryo transfer in a tertiary-referral centre. A validated smart band activity tracker was used to assess physical activity level immediately after the embryo transfer and until the pregnancy test. No specific recommendations were given to participants on level or intensity of physical activity. Physicians and patients were blinded to the data stored in the pedometer. Primary outcome was ongoing pregnancy rate. RESULTS: Fifty women met the inclusion criteria. Ongoing pregnancy rate was 30%. In a pooled analysis, participants walked significantly fewer steps per day on the day of embryo transfer compared with the first 2 days after embryo transfer (4075, interquatile range [IQR] 2932-5592 versus 5204, IQR4203-8584, P = 0.01). No significant difference was observed between pregnant women and non-pregnant women in the median steps per day after embryo transfer until serum beta-HCG was measured (7569, IQR 6008-10884 versus 6572.5, IQR 5299-8786, P = 0.43). No significant difference was observed in the median number of steps on the day of embryo transfer or the first 2 days after embryo transfer between pregnant and non-pregnant women. CONCLUSIONS: A quantitative objective assessment of the association between physical activity and pregnancy rates after frozen-thawed embryo transfer was conducted. Ambulation after embryo transfer has no adverse effect on pregnancy rates and, therefore, women should resume regular activity immediately after embryo transfer.

The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the role of intracytoplasmic sperm injection (ICSI) in the treatment of non-male factor infertile patients aged ≥ 39. METHODS: This is a single-center, prospective, randomized controlled clinical trial, between March 2018 and December 2019. Sixty-nine patients were recruited, and sixty patients participated in the study. Their ovaries were randomized prior to the beginning of the ovarian stimulation: the oocytes from one side (n = 257) were allocated to the ICSI (ICSI arm), while those of the contralateral side (n = 258) were allocated to conventional insemination (IVF arm). The fertilization rate per oocyte retrieved, number of zygotes (2PN), and cleavage-stage embryos were assessed and compared between the two study groups. RESULTS: The average number of zygotes (3.1 vs. 2.7 p = 0.45), the fertilization rate (72.4% vs. 65.1% p = 0.38), the average number of cleavage-stage (2.8 vs. 2.4 p = 0.29), and the average top-quality embryos (TQE) cleavage-stage embryos (1.7 vs. 1.6 p = 0.94) were comparable between the two groups. The TQE rate per randomized oocyte (41.2% vs. 41% p = 0.8) was also similar in both groups. CONCLUSIONS: ICSI does not improve the reproductive outcomes of advanced-age patients undergoing conventional insemination for non-male factor infertility. TRIAL REGISTRATION: NCT03370068.

Predictors of reproductive outcomes following myomectomy for intramural fibroids.

RESEARCH QUESTION: Which factors are associated with reproductive outcomes among infertile women undergoing myomectomy for intramural fibroids? DESIGN: This was a historical cohort study including 127 infertile women who underwent myomectomy due to intramural fibroids as part of fertility enhancement treatment at a single academic tertiary-care medical centre between the years 2011 and 2015. Demographic characteristics, pre-operative evaluation, surgical factors and post-surgical factors were compared between women who successfully conceived and those who did not following myomectomy. RESULTS: The overall clinical pregnancy rate following myomectomy was 58.3% (n = 74). Women with successful conception were significantly younger (35.4 ± 4.5 years versus 37.2 ± 4.0 years; P = 0.022), and mostly white (63.5% versus 24.3% African-American; P = 0.008). In addition, patients who conceived had larger fibroids demonstrated in pre-operative imaging and during surgery (7.3 versus 6.1 cm and 7.8 versus 6.6 cm; P = 0.003 and 0.022, respectively), with fewer cases of cavity entry determined during surgery (9.5% versus 28.3%; P = 0.005). Multivariable modified Poisson regression models identified the patient's age (risk ratio [RR] 0.96, 95% confidence interval [CI] 0.93-0.99; P =0.014) and race (RR for African-American women versus white women 0.58, 95% CI 0.38-0.88; P = 0.011) as factors significantly associated with the probability of conceiving following myomectomy. CONCLUSION(S): Age and race play a significant role in the reproductive outcomes of infertile women undergoing intramural fibroid myomectomy as part of fertility enhancement treatment. Further large prospective studies are needed to identify specific factors associated with achieving pregnancy, which will help to determine the clinical management of infertile women with intramural fibroids.

The expected cumulative incidence of live birth for patients starting IVF treatment at age 41 years or older.

RESEARCH QUESTION: What is the cumulative incidence of live birth (CILB) for high-order consecutive IVF cycles, and which factors are associated with live birth in women aged ≥41 years using autologous oocytes? DESIGN: A retrospective cohort study including 146 patients aged 41 years to <44 years who started their first IVF cycle attempt using autologous oocytes, between January 2006 and December 2013. RESULTS: After 13 IVF cycles, CILB reached up to 33.6%. After six IVF cycles, 42 (28.8%) women delivered a live infant (85.7% of the total live birth). Mean live birth rate per cycle declined with age at the initial cycle (8% at 41 years; 5.8% at 42 years; and 4.1% at 43 years). Multivariable modified Poisson regression models identified patient's age (RR for 41 years versus 43 years: 0.47; 95% CI 0.25 to 0.87; P = 0.01), smoking status (RR 0.21; 95% CI 0.05 to 0.08; P = 0.02), and mean number of fertilized oocytes (RR 1.23; 95% CI 1.08 to 1.39; P < 0.01) as factors significantly associated with the probability of a live birth. CONCLUSIONS: Multiple repeat IVF cycles in women aged 41-44 years offers a reasonable long-term success rate. After six cycles of treatment, about 29% of women of advanced reproductive age using autologous oocytes expected to achieve a live birth. This information might assist in fertility counselling and managing patients' expectations by adjusting the appropriate treatment strategy and number of IVF cycle attempts, especially in countries in which egg donation is prohibited or when multiple repeated IVF cycles attempts are financially affordable.

Outcome of gestational surrogacy according to IVF protocol.

PURPOSE: Surrogacy remains the only option for having a biologic child for a unique population of women with severe medical conditions. However, no study has looked at surrogacy outcome as a result of the type of ovarian stimulation of the intended mother [controlled ovarian stimulation (COH), modified natural cycle (MNC), and in vitro maturation (IVM)] for oocyte retrieval. METHODS: This is a retrospective study, including all intended mothers and gestational carriers in a tertiary, university affiliated, medical center, from 1998 to 2016. RESULTS: Fifty-two women underwent 252 oocyte retrieval cycles. The pregnancy outcome of 212 embryo transfer cycles (64 gestational carriers) was reviewed according to the origin of the embryo. The number of retrieved oocytes was significantly higher following COH (n = 132) compared with IVM (n = 58) and MNC cycles (n = 62) (p = 0.013 and p < 0.0001, respectively). Pregnancy rates for embryos transferred according to each protocol were similar. All pregnancies that ended in live births when oocytes from IVM cycles were used derived from transfers of retrieved mature and mixed mature and immature oocytes. Pregnancies that involved embryos derived solely from immature oocytes that further matured in vitro and were transferred to gestational carriers were unsuccessful. CONCLUSIONS: MNC protocol is a good option to achieve pregnancy for intended mothers using gestational surrogacy who have contraindications to COH. The yield of IVM cycles in which immature oocytes are retrieved is inconclusive.

FMR6 may play a role in the pathogenesis of fragile X-associated premature ovarian insufficiency.

The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the pathophysiology of fragile X-associated premature ovarian insufficiency (FXPOI). The study population consisted of 22 consecutive fragile X mental retardation 1 (FMR1) premutation carriers (CGGn 55-199 repeats) undergoing in vitro fertilization and pre-implantation genetic diagnosis (IVF-PGD) treatment. The control group consists of 11 patients, with <55 CGG repeats, undergoing IVF-ICSI for male factor infertility, matched by age, treated in the same period. After oocyte retrieval, granulosa cells from follicular fluid were washed and stored at -80 °C. RNA was transcribed to generate cDNA and the RNA levels were measured using RT-PCR. Transcripts levels in granulosa cells of long noncoding RNA's FMR4 and FMR6 were measured. In FMR1 premutation carriers there was a significant nonlinear association between the number of CGG repeats and the levels of FMR6 (p = 0.03), but not FMR4. The highest level of FMR6 was seen in women with mid-size CGG repeats (80-120). In addition, a significant negative linear correlation was observed between the number of oocytes retrieved and the RNA levels in granulosa cells of FMR6 (r = -0.53, p = 0.01) but not FMR4. Our study supports previous findings suggesting RNA toxic gain-of-function as one of the possible pathophysiologic mechanisms underlying FXPOI.

Treating patients with "thin" endometrium - an ongoing challenge.

OBJECTIVE: To review the literature regarding inadequate growth ("thin") of the endometrium and to present the hitherto published methods aimed to improve endometrial thickness and the consequent endometrial receptivity. MATERIALS AND METHODS: A literature review was conducted for all relevant articles assessing the effect of various treatment modalities on "thin" endometrium and the consequent reproductive outcome. RESULTS: Several treatment modalities have been offered to patients with "thin" endometrium, including hysteroscopic adhesiolysis, hormonal manipulation by estrogen and GnRH-agonist, vasoactive measures such as aspirin, vitamin E, pentoxifylline, l-arginine or sildenafil, intra-uterine infusion of growth factor such as G-CSF and the recent application of regenerative medicine. In spite of the vast diversity of treatment, most of the options accomplish only minor change in the endometrium thickness and subsequent pregnancy rate, and when they fail, patients are usually referred to surrogacy. CONCLUSIONS: "Thin" endometrium is known to adversely affect reproductive performance. Treatment of "thin endometrium" remains a challenge and future large researches are required to further elucidate and optimal management of patients with "thin" endometrium.

Reactive oxygen species in follicular fluid may serve as biochemical markers to determine ovarian aging and follicular metabolic age.

INTRODUCTION: The aim of this study was to evaluate the role of oxidative stress in the process of ovarian aging. METHODS: Follicular fluid (FF) from two randomly selected sibling follicles was collected from women undergoing in-vitro fertilization and tested for hydrogen peroxide (H(2)O(2)) levels. RESULTS: Group A consists of seven women with whom each of the two sibling separate follicle yielded an oocyte that was later discordantly developed to a low- and top-quality embryo. Group B consists of 13 patients in whom one of the sibling follicle yielded an oocyte while the other did not (empty follicle). High-quality embryos were derived from follicles with lower H(2)O(2) levels compared to follicles from which poor-quality embryos developed (1.004 units ± 0.260 versus 1.145 units ± 0.236, p < 0.02). H(2)O(2) levels were significantly higher (0.951 units ± 0.233 versus 0.623 units ± 0.309, p < 0.001) in sibling follicles containing oocyte compared to empty follicles. CONCLUSION: During the process of ovarian ageing, there might be a gradual increase in H(2)O(2) level in the follicle. Finally, when the follicle ages and becomes empty of oocyte H(2)O(2) levels drops significantly. Therefore, H(2)O(2) levels in FF may serve as a possible marker to determine ovarian aging and follicular metabolic age.

Pelvic inflammatory disease in women with endometriosis is more severe than in those without.

AIMS: To determine the incidence and severity of acute pelvic inflammatory disease (PID) or tubo-ovarian abscess (TOA) in hospitalised women with and without a history of endometriosis. METHODS: Retrospective analysis of hospital records retrieved for all women hospitalised with PID or TOA between January 2008 and December 2011 in a tertiary referral centre. Women were compared with regard to a history of endometriosis for demographic, clinical and fertility data. RESULTS: 26 (15%) of the 174 women hospitalised due to PID or TOA were excluded because of age older than 45 years, leaving 148 for analysis. The mean age was 35.7 ± 9.3 years and mean duration of hospitalisation was 5.9 ± 3.7 days. The women were divided into two groups: Group 1 with endometriosis (n = 21) and Group 2 without endometriosis (n = 127). Women in Group 1 as compared with Group 2 were significantly more likely to have undergone a fertility procedure prior to being admitted to the hospital with PID (9/27 (45%) vs 22/121 (17%), P < 0.001); particularly in vitro fertilisation (IVF) (7/ 27 (33%) vs 12/121 (9%), P < 0.006); Women in Group 1 more frequently experienced a severe and complicated course involving longer duration of hospitalisation (8.8 ± 4.7 vs 4.4 ± 2.3 days, P < 0.0001) and antibiotic treatment failure (10/27 (48%) vs 8/121 (6%), P < 0.0001). CONCLUSIONS: Pelvic inflammatory disease in women with endometriosis is more severe and refractory to antibiotic treatment, often requiring surgical intervention. It is likely that endometriosis is a risk factor for the development of severe PID, particularly after IVF treatment.

Embryos derived from single pronucleus are suitable for preimplantation genetic testing.

OBJECTIVE: To study and compare the preimplantation genetic testing for monogenic disorders (PGT-M) results, and to evaluate the treatment cycle outcomes of embryos derived from a single pronucleus (1PN) vs. two pronuclei (2PN). DESIGN: A retrospective cohort study from January 2018 to December 2022 involving in vitro fertilization (IVF)-PGT-M treatment cycles. SETTING: Single, academically affiliated fertility center. PATIENTS: A total of 244 patients underwent 351 IVF-PGT-M treatment cycles. INTERVENTION: Embryo biopsy with molecular testing for a monogenic disorder. MAIN OUTCOME MEASURES: The molecular diagnosis results and clinical outcomes after the transfer of embryos derived from 1PN and 2PN in IVF-PGT-M treatment cycles. RESULTS: Embryos derived from 1PN have a significantly low developmental potential with a lower rate of embryos that underwent biopsy compared with 2PN-derived embryos; 1PN-derived embryos demonstrated a significantly lower number of blastocysts (24% vs. 37.9%) and top-quality blastocysts (22.3% vs. 48.1%) compared with 2PN-derived embryos. Lower successfully completed and unaffected PGT-M results were achieved in 1PN compared with 2PN-derived embryos (47.1% vs. 65.5% and 18.7% vs. 31.6%, respectively), with significantly higher abnormal molecular results (39.6% vs. 22.7%). The embryo transfer of 24 1PN-derived embryos with no affected genetic disorder resulted in 5 (20.8%) clinical pregnancies and 4 (16.7%) live births (LBs). CONCLUSIONS: Within the limits of fewer embryos derived from 1PN that yielded unaffected embryos suitable for transfer, the clinical pregnancy and LB rate of 1PN embryos undergoing PGT-M are reassuring. We, therefore, suggest applying PGT-M to embryos derived from 1PN embryos to improve the cumulative clinical pregnancy and LB rates.

Multidisciplinary team approach to management of severe endometriosis affecting the ureter: long-term outcome data and treatment algorithm.

STUDY OBJECTIVE: To examine the efficiency of laparoscopic ureterolysis for ureteral endometriosis and to describe appropriate treatment. DESIGN: Prospective trial (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Forty-five patients who underwent surgery to treat ureteral endometriosis between 2005 and 2009. INTERVENTION: Laparoscopic ureteral ureterolysis. MEASUREMENTS AND MAIN RESULTS: Long-term follow up of symptoms, urinary tract anatomy and function, and the need for further intervention were performed. Ureteral endometriosis was observed in 14.2% of 315 patients with endometriosis. Of the 45 study patients, 95.5% had dysmenorrhea, 60% had dyspareunia, and 45% were infertile. Half of the patients had previously undergone laparoscopic procedures. Urinary tract symptoms were present in 15.9% of patients. Preoperative hydronephrosis or hydroureter was observed in 10 patients (22.2%), and impaired urinary function in 2 patients (4.4%). Laparoscopy demonstrated left ureteral involvement in 82.2% of patients, and deep infiltrative endometriosis in 80%. Laparoscopic ureterolysis was feasible in 91.1% of patients. In 4 patients, ureterolysis was not feasible, and primary reimplantation of the ureter was performed. Forty-one patients (91.1%) had no symptoms or had marked improvement postoperatively and required no further treatment. Two patients (4.8%) underwent repeat surgery. In 80% of patients with hydroureteronephrosis, the postoperative sonogram was normal. CONCLUSIONS: Ureteral endometriosis can be treated effectively using laparoscopic ureterolysis in almost all patients. Different treatment approaches should be based on the results of preoperative evaluation and operative findings by a multidisciplinary team. Urinary assessment is crucial because most patients demonstrate no urinary tract symptoms and initial renal investigation can prevent irreversible damage.

More is not always better-lower estradiol to mature oocyte ratio improved IVF outcomes.

AIM: To find a cut-off ratio of estradiol/metaphase II oocyte (E2/M2) ratio and to evaluate the correlation with patients' characteristics, embryo morphokinetics using EmbryoScope™ and IVF cycle outcomes. MATERIAL AND METHODS: For this retrospective cohort study, records of all fresh cycles that were cultured and scored by EmbryoScope™ were evaluated. The peak E2/M2 ratio was calculated on the day of human chorionic gonadotropin (hCG) administration and correlated to embryo morphokinetic quality and cycle outcomes. A receiver operating characteristics analysis was calculated for the E2/M2 ratio and clinical pregnancy rates. RESULTS: A total of 2461 oocytes were collected from 319 patients. Receiver operating characteristics analysis revealed a cutoff of 204 as a discriminative point to predict clinical pregnancy with a sensitivity of 69.5% and specificity of 62.1% (P < 0.001). E2/M2 > 204 group were older, had higher E2 concentration, fewer M2 oocytes despite elevated gonadotrophin doses. E2/M2 ratio ≤ 204 was correlated with higher fertilization rate, better embryo quality, higher pregnancy and live birth rates, and more frozen embryos. CONCLUSION: E2/M2 ratio < 204 yielded the best probability to achieve good quality embryos with good morphokinetic scores and better pregnancy outcomes and may be used to predict IVF cycle outcomes. Advanced maternal age and low ovarian response received higher concentrations of gonadotrophins, which resulted in higher E2/M2 ratio. Milder stimulation to those patients may improve their cycle outcomes.

Embryonic Development in Relation to Maternal Age and Conception Probability.

Data regarding association between early embryo development and maternal age is limited and inconclusive. This study has two aims: to evaluate differences in the cleavage stage of embryos in young versus advanced maternal age (AMA) women. To compare the early embryonic development of embryos that result in pregnancy versus no pregnancy. A retrospective study of early embryonic development which was recorded and analyzed using time-lapse imaging was conducted. The kinetic markers of time to pronuclei fading (tPNf) and appearance of two to eight cells (t2-t8) were assessed. For embryos cultured to blastocyst, times to morula (tM), start of blastulation (tSB) cavitated, and expanded blastocyst (tB, tEB) were also recorded. A total of 2021 oocytes from 364 intracytoplasmic sperm injection (ICSI) cycles were evaluated, of which 1223 (60.5%) were derived from young patients and 798 (39.5%) from those of AMA. The mean time points to t3, t4, t5, t6, tSB, tB, and tEB were significantly shorter for embryos derived from younger women, as compared to older women (p < 0.05). Overall, women who conceived presented a faster embryonic development, for both age groups. The mean time points of t2 and t8 were significantly shorter in patients who conceived versus not conceived (p < 0.05). We concluded that older women's age is associated with delayed embryonic development. Embryos that yielded pregnancy cleaved faster compared to those which did not, in both age groups. Thus, when considering which embryo to transfer to women of AMA, selecting the faster-developing embryos may improve the chances of conception.

Degenerated oocyte in the cohort adversely affects IVF outcome.

The presence of Degenerated Oocyte (DEG) was mostly described after intracytoplasmic sperm injection (ICSI), with fewer reports on DEG at the time of ovum pick-up (OPU). This study aims to assess morphokinetics of embryos cultured in a time-lapse incubator and compare cohorts with and without DEG at OPU. In a retrospective cohort study from January 1, 2016 until September 31, 2017 a total of 399 IVF/ICSI cycles and 2980 embryos were evaluated. In 81 of 399 cycles at least one DEG oocyte was observed at the time of OPU. The remaining 318 cycles with no DEG oocyte were compared as a control group. In the DEG group, significantly more oocytes were collected per patient (12.9 ± 7.2 vs. 10.1 ± 6.1. P < 0.001). Fertilization rate, pregnancy and clinical pregnancy rates were comparable between the two groups, however, the morphokinetics and developmental scores of the embryos were significantly worse in the DEG group, (KID 3.4 ± 1.6 vs. 3.2 ± 1.6 P = 0.002 and ESHRE 1.5 ± 1.1 vs. 1.4 ± 1.0 P = 0.046). Significantly more patients achieved top-quality embryos in the NON DEG group (58.8% vs. 53.0%, P = 0.03), however, comparable delivery rate was achieved in both groups. In the DEG group, the frequency of DEG oocyte per cycle was negatively correlated with pregnancy rate. GnRH agonist protocol and the 17-20G needle used for OPU were significant predictors for the presence of DEG oocyte at OPU. In conclusions DEG oocyte may negatively affect IVF outcome, however, younger patients, and significantly more oocytes collected in the DEG group compensate for the IVF results.

Does daily co administration of gonadotropins and letrozole during the ovarian stimulation improve IVF outcome for poor and sub optimal responders?

BACKGROUND: Co-administration of letrozole during the first 5 days of ovarian stimulation was suggested to improve IVF outcomes in poor responders. We aimed to determine whether poor/sub-optimal responders might benefit from Letrozole co-treatment throughout the entire stimulation course. METHODS: We retrospectively reviewed the medical files of women who demonstrated poor (oocyte yield ≤3) and sub-optimal (4 ≤ oocyte yield ≤9) ovarian response during conventional multiple-dose antagonist stimulation protocols and were co-treated in a subsequent cycle with 5 mg Letrozole from the first day of stimulation until trigger day. A self-paired comparison between gonadotropins-only and gonadotropins-letrozole cycles was performed. RESULTS: Twenty-four patients were included. Mean patients' age was 39.83 ± 4.60 and mean day-3-FSH was 12.77 ± 4.49 IU/m. Duration of stimulation and total gonadotropins dose were comparable between the two cycle groups. Peak estradiol levels were significantly lower in gonadotropins-letrozole cycles (2786.74 ± 2118.53 vs 1200.13 ± 535.98, p < 0.05). Number of retrieved oocytes (3.29 ± 2.15 vs 6.46 ± 3.20, p < 0.05), MII-oocytes (2.47 ± 1.65 vs 5.59 ± 3.20, p < 0.05), 2PN-embryos (1.78 ± 1.50, 4.04 ± 2.74, p < 0.05) and top-quality embryos (0.91 ± 0.97 vs. 2.35 ± 1.66, p < 0.05) were significantly higher in the gonadotropins-letrozole cycles. Clinical pregnancy rate in gonadotropins-letrozole cycles was 31.5%. CONCLUSION: Letrozole co-treatment during the entire stimulation course improves ovarian response and IVF outcomes in poor/sub-optimal responders.

The clinical value of maternal and fetal Doppler parameters in low-risk postdates pregnancies - a prospective study.

OBJECTIVE: The objective of this study is to determine the clinical significance of maternal and fetal ultrasound Doppler flow indices in postdates pregnancies. METHODS: This prospective study comprised 120 low-risk pregnant women beyond 40 weeks of gestation. All participants underwent Doppler assessment including of fetal middle cerebral artery (MCA), umbilical, and uterine arteries. Perinatal outcomes were recorded and evaluated for possible associations with Doppler flow values. Adverse perinatal outcomes were defined as umbilical cord arterial pH <7.1, Apgar score <7 at 5 min, neonatal admission to a neonatal intensive care unit, and emergency cesarean section due to abnormal intrapartum cardiotocogram Results: Adverse perinatal outcome rate was 17.5% (n = 21). Doppler indices of umbilical artery, MCA, uterine artery and the cerebroplacental ratio (CPR) did not differ significantly between pregnant women with and without adverse perinatal outcomes. Neonatal birth weight was found to correlate negatively with umbilical artery Doppler indices, including the peak systolic to end diastolic ratio (p = .04), the resistance index (p = .02), and the pulsatility index (p = .01). Doppler values of the uterine artery, MCA and CPR did not correlate with neonatal birth weight. CONCLUSIONS: The contribution of maternal and fetal ultrasound Doppler to the prediction of adverse perinatal outcomes in low-risk postdates pregnancies is low. Hence, performing routine Doppler examination as part of postdates pregnancy assessments is unlikely to yield significant clinical benefit.

Safety of low-dose prostaglandin E2 induction in grandmultiparous women with previous cesarean delivery.

OBJECTIVE: To determine the safety and efficacy of labor induction with low-dose vaginal prostaglandin E2 (PGE2) in grandmultiparous women with a previous cesarean delivery. METHODS: We conducted a retrospective cohort study of 219 grandmultiparous women with a previous cesarean delivery (study group) who underwent induction of labor with low dose PGE2. These patients were compared to 1376 grandmultiparous women without a previous cesarean section (control group) who underwent induction of labor with low dose PGE2. The primary outcome was uterine rupture and secondary outcomes included mode of delivery, post-partum hemorrhage (PPH) and a low 5-min Apgar score (≤7). RESULTS: One patient in the study group as well as one patient in the control group were diagnosed with uterine rupture (0.4% versus 0.07%). In the study group, vaginal delivery was achieved in 204 (93.16%) patients, whereas 15 (6.84%) patients had emergent cesarean delivery. Five minutes Apgar score ≤7 was recorded in two cases (0.9%) in the study group. Patients in the study group had a significantly higher rate of cesarean delivery (6.84%, versus 3.4%, respectively, p < 0.001) as well as operative vaginal delivery (4.56% versus 2% respectively, p < 0.05) compared to the control group. There were no significant differences between the groups regarding the rate of PPH (0.91% versus 0.90%, p = 0.2) or 5-min Apgar score ≤7 (0.91% versus 0.22%, p = 0.28). CONCLUSIONS: Low dose PGE2 is a relative safe method for induction of labor in grandmultiparous women with a previous cesarean section.

Elevated levels of FMR1 mRNA in granulosa cells are associated with low ovarian reserve in FMR1 premutation carriers.

AIM: To assess the role of mRNA accumulation in granulosa cells as the cause of low ovarian response among FMR1 premutation carriers undergoing pre-implantation genetic diagnosis (PGD). DESIGN: Case control study in an academic IVF unit. Twenty-one consecutive FMR1 premutation carriers and 15 control women were included. After oocyte retrieval the granulosa cells mRNA levels of FMR1 was measured using RT-PCR. RESULTS: In FMR1 premutation carriers, there was a significant non-linear association between the number of CGG repeats and the number of retrieved oocytes (p<0.0001) and a trend to granulosa cells FMR1 mRNA levels (p = 0.07). The lowest number of retrieved oocytes and the highest level of mRNA were seen in women with mid-size CGG repeats (80-120). A significant negative linear correlation was observed between the granulosa cells FMR1 mRNA levels and the number of retrieved oocytes (R2 linear = 0.231, P = 0.02). CONCLUSION: We suggest that there is a no-linear association between the number of CGG repeats and ovarian function, resulting from an increased granulosa cells FMR1 mRNA accumulation in FMR1 carriers in the mid-range (80-120 repeats).