Surgically retrieved spermatozoa versus ejaculated spermatozoa in modified natural IVF–ICSI cycles

A retrospective cohort study was performed to evaluate the outcome of modified natural IVF–intracytoplasmic sperm injection (mnIVF–ICSI) cycles to compare 81 mnIVF–ICSI first cycles using ejaculated spermatozoa with 44 mnIVF–ICSI first cycles using surgically retrieved spermatozoa. There were no differences between the two groups in terms of number of oocytes retrieved, oocyte maturity or female age. However, male age was significantly higher in the surgically retrieved compared with the ejaculated group (41.5 versus 36.5 years, P = 0.001). There were no significant differences in fertilization rate or cleavage rate between the ejaculated and the surgically retrieved groups; however the prevalence of embryo transfer was higher in the surgically retrieved group (65.9% versus 45.7%, P = 0.03). Only single-embryo transfer was performed. Biochemical (34.5% versus 37.8%) and clinical (31.0% versus 35.1%) pregnancy rates per embryo transfer were similar between the ejaculated and the surgically retrieved groups. The data suggest that mnIVF–ICSI is an alternative treatment option in couples with severe male factor infertility where surgical sperm retrieval is required.The aim of the present study was to evaluate and compare the outcomes of modified natural IVF–intracytoplasmic sperm injection (mnIVF–ICSI) with surgically retrieved spermatozoa (in male partners with obstructive azoospermia) and ejaculated spermatozoa (in couples with mild-to-moderate male factor). Eighty-one mnIVF–ICSI first cycles using ejaculated spermatozoa were compared with forty-four mnIVF–ICSI first cycles using surgically retrieved spermatozoa. There were no differences between the two groups in terms of number of oocytes retrieved, oocyte maturity or female age. However, male age was significantly higher in the surgically retrieved compared with the ejaculated group. There were no significant differences in fertilization rate, or cleavage rate between the two groups; however, there were more patients having embryo transfers in the surgically retrieved group. Only single-embryo transfer was performed. Biochemical and clinical pregnancy rates per embryo transfer were similar between both groups. The data suggest that mnIVF–ICSI is an alternative treatment option in couples with severe male factor infertility where surgical sperm retrieval is required.     

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.

     

Trends in primeval β-hCG level increment after fresh and frozen-thawed IVF embryo transfer cycles

Mid-trimester beta-human chorionic gonadotropin (BHCG) levels are considerably higher in pregnancies resulting from frozen embryo transfer (FET) compared with fresh (FRET), leading to a higher false positive rate in aneuploidy screening tests. We aimed to investigate the dynamics of BHCG increment and its predictive value for cycle outcome. A retrospective analysis of FRET and FET cycles. BHCG values on days 14 and 16 post embryo transfer were compared and stratified according to the number of sacs demonstrated on US scan at six weeks gestation, and pregnancy outcome (biochemical pregnancy, ectopic pregnancy, spontaneous abortion, and a singleton or twin birth). A prediction model for live birth was built. A total of 430 treatment cycles were analyzed. The average BHCG levels were significantly higher in FET compared with FRET group in nonviable pregnancies on day 14, 450 vs. 183?IU/L, p?<?.05 and day 16, 348 vs. 735?IU/L, p?<?.05, respectively. The increment of BHCG was significantly steeper in the FET compared with FRET group in biochemical pregnancies (F?=?6.485, p?=?.012*). Optimal cutoff level for live birth prediction in the FRET group was 211?IU/L (sensitivity 84%, specificity 76.2%) for day 14 and 440?IU/L (sensitivity 86.0% and specificity 72.5%) for day 16. The increment in BHCG differed significantly between the FRET and FET cycles in nonviable pregnancies. Nevertheless, the difference in BHCG levels observed in the second trimester in pregnancies conceived after FRET and FET cycle may begin as early as the fourth week of pregnancy.     

Effect of chromosomal polymorphisms of different genders on fertilization rate of fresh IVF–ICSI embryo transfer cycles

To explore whether chromosomal polymorphisms of different genders affect outcomes of fresh IVF and intracytoplasmic sperm injection (ICSI) embryo transfer cycles differently, 37 couples with chromosomal polymorphisms were identified out of 614 infertile couples undergoing IVF–ICSI treatments. Group 1 included 20 couples in which only the male carried chromosomal polymorphisms; group 2 included 17 couples with female carriers only; group 3 included 19 infertile couples with normal karyotypes randomly selected as controls. A significantly lower fertilization rate was found in group 1 compared with groups 2 and 3 (56.68% in Group 1, 78.02% in group 2 and 71.74% in group 3; group 1 versus group 2, P < 0.001; group 1 versus group 3, P = 0.001; respectively). When stratified according to fertilization method, the fertilization rate in IVF cycles of group 1 was significantly lower than group 3 (50.00% in Group 1, 73.89% in Group 3, P < 0.001). Fertilization rates in ICSI cycles between groups 1 and 3 were not significantly different. This study suggests that male chromosomal polymorphisms adversely influence fertilization rates of IVF cycles. The use of ICSI may improve the success of infertility treatment by increasing the fertilization rate for men with chromosomal polymorphisms.     

Day 6 blastocyst is associated with increased birth weight in full-term singleton newborns after frozen–thawed transfer

Purpose

The purpose of the study is to compare the newborns weight in singleton term birth following transfer of thawed blastocysts–frozen on either day 5 or day 6 after in vitro fertilization.

Method

The retrospective study included 1444 frozen–thawed blastocyst transfer (FBT) cycles resulting in live singleton births between Jan 2013 and Dec 2016. The main outcomes measured were absolute birth weight, z-score adjusted for gestational age and gender, and incidence of large-for-gestational-age (LGA) newborns. Generalized linear model (GLM) and logistic regression were used in multivariate analyses.

Result(s)

Both the absolute birth weight (3416.49?±?404.74 vs 3349.22?±?416.17) and the z-score (0.6?±?0.93 vs 0.41?±?0.93) were significantly higher on day 6 FBT in comparison with day 5 FBT. The incidence of LGA newborns was also increased on day 6 FBT (22.8 vs 14.7%, P?=?0.006). Adjusted for maternal age, BMI, PCOS diagnosis, present of vanishing twin, and embryo quality, the odds ratio (95% confidence interval) for LGA on day 6 FBT comparing with day 5 FBT was 1.76 (1.18–2.64).

Conclusion(s)

Day 6 FBT is associated with increased birth weight and contributes to the incidence of LGA newborns in FBT.

     

Does IVF cleavage stage embryo quality affect pregnancy complications and neonatal outcomes in singleton gestations after double embryo transfers?

Purposes

Embryo quality is associated with successful implantation and live births. Our retrospective study was carried out to determine whether or not cleavage stage embryo quality affects the miscarriage rate, pregnancy complications and neonatal outcomes of singletons conceived with assisted reproduction technology.

Method

The current study included 11,721 In Vitro Fertilization-Embryo Transfer cycles (IVF-ET) between January 2009 (the date at which electronic medical records were implemented at our center) and March 2013. Only women < 40 years of age undergoing their first fresh embryo transfer cycle using non-donor oocytes were included.

Results

Our study indicated that the transfer of poor-quality embryos resulted in higher miscarriage (19.77 % vs. 13.28 %, p = 0.02) and lower ongoing pregnancy rates (15.33 % vs. 48.06 %, p < 0.001). Logistic regression analysis performed on data derived from 744 cycles culminating in miscarriages versus 4,333 cycles culminating in live births, suggested that embryo quality (p = 0.04) is significantly associated with miscarriage rate after adjusting for other confounding factors. Moreover, there were no differences in the mean birth weight, low birth weight (<2,500 g), very low birth weight (<1,500 g), gestational age, preterm delivery (<37 weeks), very preterm delivery (<32 weeks), congenital malformations, small-for-gestational-age singletons (SGA), and large-for-gestational-age singleton (LGA) rate (p > 0.05). Similarly, pregnancy complications resulting from poor-quality embryos were not different from good-quality embryos (4.04 % vs. 2.57 %, p = 0.33). Finally, logistic regression suggested that embryo quality was not significantly associated with pregnancy complications after adjusting for other confounding factors (p = 0.40).

Conclusions

Our study suggests that transfer of poor-quality embryos did not increase the risk of adverse outcomes; however, the quality of cleavage stage embryos significantly affected the miscarriage rate and ongoing pregnancies.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-014-0351-8) contains supplementary material, which is available to authorized users.     

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.     

Association between the number of oocytes retrieved and cumulative live birth rate in women aged 35–40 years undergoing long GnRH agonist IVF/ICSI cycles

Purpose

To study the association between the numbers of oocytes retrieved and the cumulative live birth rates (LBR) in women aged 35–40 years undergoing long GnRH agonist IVF/ICSI cycles.

Methods

A total of 931 women aged 35–40 years who underwent their first cycle of IVF/ICSI treatment between January 2010 and December 2013 at Nanjing Drum Tower Hospital were identified and reviewed. The main endpoint of this study was the cumulative LBR after one complete oocyte retrieval, which included fresh and all subsequent frozen–thaw embryo transfer cycles. Odds ratios (OR) and 95% confidence interval (CI) for live birth were estimated by multivariate logistic regression analysis. Furthermore, all the women were divided into four groups based on the number of oocytes retrieved: 0–4, 5–9, 10–14 or ≥15 oocytes group. Variables were then compared among groups.

Results

We found that 634 out of the 931 patients (68.1%) achieved at least one live birth. The number of oocytes retrieved was an independent predictive factor for live birth, with OR 1.20 (95% CI 1.15–1.26) when adjusted for age (years), duration of infertility and Gn (gonadotrophin) doses. The cumulative LBR in the four different oocyte groups was 35.6, 68.8, 83.4 and 89.2%, respectively. When the 1–4 oocytes group was issued as a reference, the ORs for cumulative LBR gradually increased to 3.66, 6.74 and 11.77 in other three oocytes groups, respectively. The moderate–severe ovarian hyperstimulation syndrome (OHSS) rate was dramatically increased in the ≥15 oocytes group (6.9%) when compared to that in the 10–14 oocytes group (0.8%), while the cumulative LBR only increased 5.8% (from 83.4 to 89.2%).

Conclusions

The ideal number of oocytes retrieved in women aged 35–40 years is 10–14 oocytes, which achieves a high cumulative LBR while maintaining an acceptable low OHSS rate.

     

Assessment of maternal–fetal status of some essential trace elements in pregnant women in late gestation: relationship with birth weight and placental weight

Objective: The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal–maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population.

Methods: Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry.

Results: The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2?μg/l, respectively, in maternal venous blood in the pregnant women (n?=?39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p?>?0.05) in the mother–child pairs studied. However, neonatal weight correlated negatively (p?<?0.05) with umbilical venous Cu level. Placental weight correlated positively (p?<?0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood.

Conclusions: Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.     

Ovarian reserve in young women with low birth weight and normal puberty: a pilot case–control study

Aim.?Studies indicate that women born small for gestational age (SGA) have impaired ovarian function. The origin of this ovarian dysfunction is still debatable. The aim of this study was to compare ovarian ageing between girls born appropriate for gestational age (AGA) and SGA. Therefore, we measured Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), E2, Anti-Müllerian hormone (AMH) levels and the pituitary response to endogenous Gonadotropin-releasing hormone (GnRH) in adolescent girls born SGA and AGA.

Methods.?A case–controlled pilot study consisting of seven SGA women (birth weight?<10th percentile AGA) and 13 AGA women with regular menstrual cycles, age 19.9 (±0.42). Early follicular FSH, LH, Oestradiol (E2) and AMH levels were measured. After baseline samples, 100?μg GnRH was administered intravenously and at 30, 60 and 90?min blood samples were taken to measure gonadotropin levels and to compute the response to endogenous GnRH.

Results.?Mean follicular phase LH, FSH, E2 and AMH levels did not significantly differ between young women born SGA and AGA. Furthermore, the response to endogenous GnRH showed no significant differences either.

Conclusions.?We concluded against extension of this pilot study. Based on our observations it seems unlikely that limited ovarian reserve is a predominated problem in adolescent SGA.     

IGF2/ApaI polymorphism associated with birth weight in children of the region of Petrolina–PE,Brazil

Insulin-like growth factor 2 (IGF2) gene has an important role in fetal growth. It was investigated association of the IGF2/ApaI polymorphism with low birth weight and normal birth weight (as control) in children attended in Hospital Dom Malan Petrolina, PE-Brazil. The genotype frequencies did not differ statistically between low birth weight (AA = 16.22%, AG = 43.24%, GG = 40.54%) and control (AA = 20% AG = 35%, GG= 45% groups) and the allele frequencies were not significantly different (p > 0.05).The observed genotype frequencies in both groups did not deviate significantly from Hardy–Weinberg equilibrium. Then, no significant correlation was found for this polymorphism in the population studied.     

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.     

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.     

The dilemma of counseling patients about poor prognosis: live birth after IVF with autologous oocytes in a 43-year-old woman with FSH levels above 30 mIU/mL

Providing reasonable expectations to patients with diminished ovarian reserve prior to attempting pregnancy through in vitro fertilization (IVF) is one of the most challenging aspects of fertility care. In some instances, advice from the clinician to pursue more effective treatment, such as donor oocytes, may not be acceptable to the patient. In this case report, a patient is presented who represents a poor prognosis candidate for IVF treatment. She was 43 years old with six prior failed IVF cycles and repetitive basal FSH values above 30 mIU/mL. Presented are the challenges in patient counseling and decision making. In her seventh IVF cycle, which she was strongly counseled against pursuing, the patient experienced the desired outcome of live birth. Increasing reports are emerging of live birth using autologous oocytes among women of advanced reproductive age. These instances, as well as the case of our patient, raise issues commonly encountered in patient counseling in poor prognosis patients. This discussion should include an emphasis on patient goals as well as an acknowledgement that no test for ovarian reserve has a 100% positive predictive value.     

Association between small for gestational age and low birth weight with attention deficit and impaired executive functions in 3–6 years old children

Background: Behavioral disorders and attention deficit hyperactivity disorder (ADHD) symptoms are frequently reported among children with history of small body size at birth and disproportionate intrauterine growth retardation. The current study aimed to investigate some factors like executive functions and attention deficit in children with history of Small for gestational age (SGA) and/or Low Birth Weight (LBW) at birth.

Methods: A historical cohort study was done and 3–6 years old preschool children (with past history of SGA/LBW) from some kindergartens and health centers were selected. Control group was randomly selected among children with history of normal birth weight and appropriate for gestational age at birth. All children were interviewed by an expert psychologist. Variables related to their attention, development, and executive functions were assessed by ASQ, Conner’s, and Wisconsin Card Sorting Test. Completed questionnaires related Attention deficit and indexes of executive functions were evaluated between children in case groups and their counterparts in controls.

Results: Based on inclusion criteria, 229 preschool children entered the study. With regard to size for gestational age, 124 cases were categorized in the SGA/LBW group and the rest were assigned in the appropriate for gestational age (AGA) group. In the case group, NPE and Percent Perseverative Errors (PPE) scores were significantly lower than normal birth weight group (p?=?.0001, p?=?.015). Scores related B item of Conner’s was significantly different between cases and their controls (p?=?.039, p?=?.035).

Conclusions: Our results indicated that children with past history of some risks at birth may suffer from complications related attention and executive functions in their childhood. Recommendations for further research are strongly suggested.     

Symptoms of post‐traumatic stress disorder in couples after birth: association with the couple's relationship and parent–baby bond

Recent research suggests a proportion of women develop post‐traumatic stress disorder (PTSD) after childbirth. To date, the effects of postnatal PTSD on the couple's relationship and the parent–baby bond have not been examined. In the present study, 64 couples completed questionnaires about the birth, symptoms of PTSD, the couple's relationship and parent–baby bond 9 weeks after childbirth.

Results showed 5% of men and women had severe symptoms of PTSD. Symptoms were strongly associated within couples and were related to similar birth factors for men and women. PTSD symptoms were associated with neither the parent–baby bond nor couple's relationship. The mother–baby bond was not associated with any variables measured in this study. However, the father–baby bond was associated with the couple's relationship. It is concluded that men and women have comparable levels of PTSD symptoms 9 weeks after birth. Furthermore, these results suggest postnatal symptoms of PTSD have little association with the couple's relationship or the parent–baby bond in the short term. However, further research is needed to address methodological considerations.     

Reduction in multiple pregnancy rate in donor oocyte–recipient gestational carrier (GC) in vitro fertilization (IVF) cycles in the USA with single-embryo transfer and preimplantation genetic testing

Purpose

To evaluate the utilization of single-embryo transfer (SET) and preimplantation genetic testing (PGT) in gestational carrier IVF cycles in the USA with donor oocyte and examine the impact on live birth and multiple gestation.

Methods

Retrospective cohort study using the Society of Assisted Reproductive Technology (SART) clinic database of 4776 donor oocyte–recipient IVF cycles in which a GC was used. The cycles were separated into 4 groups by use of PGT and number of embryos transferred as follows: (1) PGT and single-embryo transfer (PGT-SET); (2) PGT and multiple embryo transfer (PGT-MET); (3) no PGT and SET (NoPGT-SET); (4) no PGT and MET (NoPGT-MET). Primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR).

Results

More than one blastocyst was transferred in 48.7% (2323/4774) of the cycles. When ≥1 blastocyst was transferred, with or without the use of PGT, the MPR was 45.5% and 42.0%, respectively. In comparison, in the PGT-SET and NoPGT-SET groups, the MPR was 1.4% (8/579) and 3.3% (29/883), respectively. Live birth rates increased with the use of PGT-A and with MET.

Conclusion

This study shows that SET, with or without PGT, is associated with a significantly reduced MPR in donor oocyte–recipient GC IVF cycles while maintaining high LBR. It also demonstrates that many infertility centers in the USA are not adhering to ASRM embryo transfer guidelines. Our findings highlight an opportunity to increase GC safety, which ultimately may lead to widened access to this increasingly restricted service outside the USA.