Does the type of GnRH analogue used,affect live birth rates in women with endometriosis undergoing IVF/ICSI treatment,according to the rAFS stage?

Since the introduction of gonadotropin-releasing hormone (GnRH) antagonists, an extensive amount of literature investigating the role of the downregulation protocols on pregnancy outcomes has been published. However, these studies were mainly performed in the general infertile population where patients with endometriosis were often excluded or underrepresented. This study is a large retrospective cohort study including 386 endometriosis patients undergoing IVF/ICSI, who had been previously classified according to the rAFS system. Patients were stimulated either a long GnRH agonist or GnRH antagonist protocol. Depending on endometriosis stage, patients were divided into two groups: endometriosis stage I–II and endometriosis stage III–IV. Each group was subdivided, based on the type GnRH analog used. When comparing the GnRH agonist and antagonist groups, patients with endometriosis stage I–II, had a tendency toward higher β-hCG positive, clinical pregnancy, and live birth rates (42.8% vs. 26.7%; p?=?.07) in favor of GnRH agonist use. In endometriosis stage III–IV, no differences were observed between agonist and antagonist cycle in any of the pregnancy outcomes. Multivariate regression analysis did not reveal any significant predictor of live birth after adjusting for relevant confounders. Based on our findings, the chance to have a liveborn in endometriosis population seems not to be affected by the type of GnRH analog used, at least in advanced stages. Findings from stage I–II endometriosis cases merit consideration and further evaluation in a larger sample size is warranted.     

Does the degree of hypothalamic-pituitary-ovarian recovery after oral contraceptive pills affect outcomes of IVF/ICSI cycles receiving GnRH-antagonist adjuvant therapy in women over 35?years of age?

Purpose

To evaluate if the degree of recovery of serum gonadotropins after oral contraceptive pills (OCP) pretreatment has an impact on ovarian response in GnRH-antagonist IVF cycles in women of advanced maternal age.

Methods

In this retrospective cohort study, we included 98 women 35–42 years undergoing their first IVF cycle receiving gonadotropins and a fixed GnRH-antagonist adjuvant protocol. Data analysis was carried out according to changes in serum FSH, LH and estradiol (E₂) levels (basal and post-OCP) divided in quartiles, and also according to absolute levels. The main outcomes were peak serum E₂, number of mature oocytes retrieved, length of stimulation, and amount of gonadotropins used.

Results

By quartile analysis, patients with the highest levels of serum gonadotropins suppression and also patients with gonadotropin rebound needed larger amounts of LH during the treatment. On the other hand, women with absolute suppression of FSH/LH had increased length of stimulation.

Conclusions

The results of this study provide data that assist in clinical management. Gonadotropin serum levels after OCP treatment provide information for optimization of supplementation with LH in GnRH-antagonist cycles in women over age 35.     

Multiple cryopreservation–warming cycles,coupled with blastocyst biopsy,negatively affect IVF outcomes

Research questionDo multiple cryopreservation–warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes?DesignPatients undergoing IVF with homologous single embryo transfer, and who underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) between 2013 and 2017, were divided into three groups based on degree of embryonic micromanipulation: once-biopsied, once-cryopreserved (group BC, n = 2603), once-biopsied, twice-cryopreserved (group CBC, n = 95) and twice-biopsied, twice-cryopreserved (group BCBC, n = 15). The primary outcome was live birth; secondary outcomes included positive serum pregnancy test, clinical pregnancy and miscarriage.ResultsGroup CBC had a significantly lower chance of live birth (adjusted RR 0.57, 95% CI 0.41 to 0.79) and clinical pregnancy (adjusted RR 0.67, 95% CI 0.53 to 0.85) compared with group BC. Miscarriage rates were similar between groups BC and CBC (adjusted RR 1.3, 95% CI 0.64 to 2.7).ConclusionsMultiple cryopreservation–warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes. Although PGT-A is thought to improve reproductive outcomes on a per transfer basis, caution must be exercised in counselling patients on the possibility of diminishing returns owing to further embryonic micromanipulation after an embryo has been cryopreserved.     

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

Research questionWhat are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF?DesignA 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.ResultsSalivary 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).ConclusionIt 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.     

Does the genetic and familial background of males undertaking ICSI affect the outcome?

Purpose  To investigate whether the success rate of ICSI is (1) related to the etiology of infertility or (2) adversely affected by a family history of potential genetic disorders. Methods  All men with an ICSI indication in our hospital between 1994 and 2005 were included in our cohort study. Data on the ICSI process, etiology of infertility, and family history were collected. ICSI success rates of infertility subgroups and a subgroup with a positive family history were compared to a group with unknown etiology and a negative family history. Results  There was no significant difference in clinical pregnancy or delivery rates between the subgroups. Couples achieving a pregnancy underwent significantly more ICSI cycles compared to couples not achieving a pregnancy. Conclusion  Our results suggest that the success rate of ICSI treatment is not related to the cause of infertility or a family history positive for potential genetic disorders. Capsule ICSI success rate is neither related to the cause of infertility nor adversely affected by a family history positive for potential genetic disorders.     

The effect of chromosomal polymorphisms on the outcomes of fresh IVF/ICSI–ET cycles in a Chinese population

Purpose

Chromosomal polymorphisms (CPs) have been reported to be associated with infertility; however, their effects on the outcomes of in vitro fertilization/intracytoplasmic sperm injection–embryo transfer (IVF/ICSI–ET) are still controversial. In this retrospective study, we aimed to evaluate the effect of CPs on IVF/ICSI–ET outcomes.

Methods

To investigate whether CPs affected the outcomes of fresh IVF/ICSI–ET cycles in a Chinese population, we evaluated infertile couples with male carriers of CPs (n?=?348), infertile couples with female carriers (n?=?99), and unaffected couples (n?=?400) who had received their first treatment cycles in our hospital between January 2013 and March 2015.

Results

CPs in either male or female carriers seemed to have adverse effects on IVF/ICSI–ET outcomes. CPs in male carriers affected outcomes mainly by decreasing the rates of fertilization, embryo cleavage, good quality embryos, clinical pregnancies, ongoing pregnancies, and deliveries as well as increasing the biochemical pregnancy rate (P?<?0.05); CPs in female carriers affected outcomes only by lowering the embryo cleavage rate (P?<?0.05). The mean fertilization rate of couples with male CP carriers undergoing IVF was significantly lower than that in those undergoing ICSI (61.1 versus 66.5 %, respectively; P?=?0.0004).

Conclusions

Our data provide evidence for the involvement of CPs in the poor outcomes of fresh IVF/ICSI–ET cycles in a Chinese population. The use of ICSI might improve outcomes by increasing the fertilization rate for men with CPs.

     

Does diurnal variation affect the first trimester fetal aneuploidy screening test biochemical parameters of fetuses with normal nuchal translucency?

Objective: The purpose of this study was to investigate the effect of diurnal variation on biochemical results of first trimester aneuploidy screening test.

Methods: A total of 2725 singleton pregnant female, who had normal fetal nuchal translucency (NT) thickness, were included in the study during this period. Individuals were divided into two groups according to the sampling time (morning group: 09:00–11:00 am and afternoon group: 02:00–04:00?pm). Hormonal parameters (free-beta human chorionic gonadotropin [free β-hCG] and pregnancy-associated plasma protein-A [PAPP-A] multiples of median [MoM] levels) of first trimester (11⁺⁰–13⁺⁶ weeks) combined aneuploidy screening test were compared between morning and afternoon groups.

Results: PAPP-A MoM levels were significantly lower in the afternoon group when compared to the morning group (p?=?0.001), whereas free β-hCG MoM levels were similar in the both groups (p?=?0.392). Rate of high risk for Down syndrome (Combine risk >1/300) and amniocentesis ratio were found higher in the afternoon group than morning group, but there were no difference between groups for the number of fetuses with Down syndrome.

Conclusion: Receiving the venous blood sample for first trimester aneuploidy screening test in the afternoon causes low PAPP-A MoM levels.     

Does subtle progesterone rise on the day of HCG affect pregnancy rate in long agonist ICSI cycles?

Purpose  To evaluate the impact of subtle progesterone (P4) rise on the day of HCG on pregnancy outcome in ICSI patients stimulated with long agonist protocol. Methods  One hundred forty-nine consecutive controlled ovarian hyperstimulation cycles for ICSI using long luteal agonist protocol. Results  Mean serum progesterone on day of hCG was 0.88±0.51 ng/mL values ≥1 ng/mL were found in 34.2% of cycles. Serum E2 on day of hCG and number of oocytes retrieved were significantly higher in the group with P4 ≥ 1 ng/mL. The area under ROC for serum progesterone in prediction of pregnancy was 0.52, indicating that within the values studied, serum progesterone on day of hCG is not predictive of pregnancy outcome. Conclusion  P4 values ≥1 ng/mL on day of hCG are common in long agonist ICSI cycles particularly with high response. Within the P4 values encountered in this study, implantation and pregnancy rates are not adversely affected. Capsule   Pre-hCG, subtle progesterone rise is common in high response long agonist ICSI cycles, and is not associated with lower pregnancy rate.     

Association between the number of top-quality blastocysts and live births after single blastocyst transfer in the first fresh or vitrified–warmed IVF/ICSI cycle

Research questionIs there an association between the total number of top-quality blastocysts (TQB) developed in the first IVF/intracytoplasmic sperm injection cycle (ICSI) and live births after a single blastocyst transfer (SBT)?DesignPregnancy outcomes from 1336 infertile women who had undergone their first IVF/ICSI treatment and accepted a first-time embryo transfer with a single fresh or vitrified–warmed blastocyst between January 2016 and August 2018 were assessed retrospectively. The restricted cubic splines method was used to evaluate the association between the number of TQB, and ongoing pregnancies and live births.ResultsA significant non-linear functional form was found between the number of TQB and the ongoing pregnancies and live births (P < 0.05). The odds of an ongoing pregnancy or live birth were similar, at about 11% or higher for each additional TQB up to five TQB (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.01–1.21). After this, pregnancy outcomes nearly plateaued, indicating that the number of TQB was not related to pregnancy when it was greater than five.ConclusionsThe quantity of TQB available for transfer or cryopreservation can provide important predictors for pregnancy and live birth after the first embryo transfer cycle with a single blastocyst. This valuable information may assist with the future application of SBT.     

Is the Zona pellucida thickness of metaphase-II oocytes in an IVF/ICSI program influenced by the patient's age?

Objective: This study examined the influence of weather conditions on the incidence of outpatient emergency consultations at the Department of Obstetrics and Gynecology at the Regional Hospital in Lugano, Switzerland. Study Design: The medical records of all women who attended the outpatient emergency unit at the Department for Obstetrics and Gynecology over the 1-year study period were reviewed. The final diagnosis was pelvic pain of unidentified origin in 180 cases, menorrhagia and/or metrorrhagia in 95 cases, threatened abortion in 56 cases and spontaneous abortion in 54 cases. The meteorological factors considered were atmospheric pressure, temperature, humidity and global radiation. A logistic regression model was used to correlate the occurrence of symptoms with the chosen weather factors. Results: High mean daily temperature was found to be a significant predictor of pelvic pain (p < 0.001). A rise in barometric pressure compared to the previous day increased the probability of menorrhagia and/or metrorrhagia (p = 0.001). Higher minimal temperature (p = 0.011) and an increase in atmospheric pressure (p = 0.006) were identified as positive predictors of threatened abortion. None of the meteorological factors considered seemed to influence the frequency of spontaneous abortions. Conclusion: Meteorological factors such as temperature and barometric change appear to affect the probability of emergency admissions for gynecological symptoms including uterine bleeding, threatened abortion and pelvic pain.     

Does the risk of cerebral palsy increase or decrease with increasing gestational age?

Background  

It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective.     

Turner's syndrome and pregnancy: has the 45,X/47,XXX mosaicism a different prognosis? Own clinical experience and literature review

Turner's syndrome is characterized by an ovarian failure which occurs in most cases before puberty and leads to infertility. In less than 10% of women with Turner syndrome, puberty may occur and spontaneous pregnancies is possible but with a high risk of fetal loss, chromosomal and congenital abnormalities. We present the case of a 33-year-old woman with a mosaic Turner's syndrome karyotype 45,X/47,XXX who conceived spontaneously and had two successful pregnancies. Short stature was the only manifestation of Turner's syndrome. In the present report, we reviewed the available literature on the fertility of women with Turner's syndrome and the phenotypic effects of mosaicism for a 47,XXX cell line in Turner's syndrome.     

Does the addition of clomiphene citrate or letrazole to gonadotropin treatment enhance the oocyte yield in poor responders undergoing IVF?

Purpose  

To evaluate the effect of adjunctive letrazole or clomiphene in IVF stimulation protocols.