Do paternal semen parameters influence the birth weight or BMI of the offspring? A study from the Utah Population Database

Purpose

To study the role of individual semen parameters on the offspring birth weight and body mass index (BMI) from a population of men evaluated in an assisted reproduction technology (ART) clinic compared to fertile controls.

Methods

We performed a retrospective study using a cohort with fertile, age-matched controls of men evaluated with semen analysis at the University of Utah Andrology Clinic from 1996 to 2011 and Intermountain Healthcare from 2002 to 2011. We use the offspring from both our sub-fertile cohort and controls using the Utah Population Database. The two main outcomes of interest were offspring birth weight and adolescent BMI.

Results

The offspring of men with impaired sperm parameters had significantly lower birth weight compared to fertile control offspring. Low-concentration offspring weighed 158 g less (95% CI ??278~??38; p?=?0.01), low total count weighed 172 g less (95% CI ??294~??51; p?=?0.005), and low total motility weighed 155 g less (95% CI ??241~??69; p?<?0.001) compared to those of the controls. When we controlled for the use of ART within the sub-fertile group, we found that there was a significant trend of increasing birth weight across levels of total motile count and total sperm count compared to the azoospermic group. We did not find any consistent significant differences between the subject and control adolescence BMI based on semen parameters.

Conclusions

Despite limitations within our population-based dataset, we found that poor quality semen analysis parameters pointed towards an association with low birth weight in the offspring of sub-fertile men compared to the offspring of normal fertile controls. However, in contrast to studies of ART effects on offspring, we did not find evidence of long-term associations between semen quality and offspring BMI.

     

Impact of the <Emphasis Type="Italic">FSHB</Emphasis> gene -211G/T polymorphism on male gonadal function

Purpose

The FSHB gene -211G/T polymorphism has been reported to modulate gene expression and to cause inter-individual differences in FSH serum levels in men. This study was undertaken to assess the functional relevance of this polymorphism on gonadotropin and total testosterone serum levels and sperm parameters in men from Eastern Sicily (Italy).

Methods

To accomplish this, 200 men with abnormal conventional sperm parameters or normozoospermia (according to the parameters of WHO 2010) were genotyped by TaqMan Assay.

Results

The frequency of FSHB -211 T allele was significantly higher (p < 0.005) in patients with altered conventional sperm parameters (18.9% of chromosomes) compared to that observed in men with normozoospermia (10.9% of chromosomes). Decreasing serum levels of FSH and LH were observed across the three FSHB -211 genotype subgroups (p < 0.001 and p < 0.05, respectively). In addition, the FSHB -211G/T polymorphism showed a total testosterone downward trend that became more evident in men with the TT genotype compared to subjects with the GG genotype (p = 0.05). Furthermore, we found a trend towards decreased sperm concentration, total sperm count, sperm forward motility and testicular volume in men with GT and TT genotypes.

Conclusions

These findings showed that the FSHB -211 G/T polymorphism modulates male gonadal function with a clear influence on hormonal levels and sperm parameters.

Capsule

The present study was undertaken to evaluate the distribution of the FSHB -211 G/T in men with normal or abnormal sperm parameters from Southern Italy to assess its functional relevance on the serum levels of reproductive hormones and on sperm parameters in men.

     

Egg donation of vitrified oocytes bank produces similar pregnancy rates by blastocyst transfer when compared to fresh cycle

Purpose

Advances in reproductive techniques, mainly the introduction of oocyte vitrification, have provided the opportunity to conceive from oocyte banks. The aim of this study was to compare the clinical outcomes of fresh and vitrified oocytes in an egg donation program following blastocyst transfer.

Methods

This retrospective observational study included 504 oocyte donation cycles. All donor women were younger than 30 years of age. The recipient cycles were divided into two groups: fresh oocytes (n = 78) or vitrified oocytes (n = 426). All oocytes were fertilized by ICSI using ejaculated sperm, followed by blastocyst transfer. Endometrium preparation was performed with estradiol valerate plus micronized progesterone according to standard protocols.

Results

Recipients were of similar age (fresh 42.0 ± 4.5 years vs vitrified 41.8 ± 4.8 years; p = 0.790). The fresh group received more mature oocytes for injection compared to the vitrified group (10.1 ± 2.8 vs 9.2 ± 2.2; p = 0.005). The two pronuclei (2PN) rate (74.5 vs 77.4%; p = 0.195) and blastocyst rate (48.8 vs 51.6%; 0.329) were similar between the fresh and vitrified groups, respectively. The rates of clinical pregnancy were 60.9% in the fresh and 59.0% in the vitrified groups (p = 0.771).

Conclusions

Our findings suggest that vitrified oocytes result in similar pregnancy rates when compared to fresh oocytes with blastocyst transfer in an egg donation program. Moreover, vitrified oocytes may allow for a better cycle schedule, starting with a lower number of oocytes to be fertilized. Therefore, we hypothesize that egg banks with vitrified oocytes could be safely utilized in an egg donation program.

     

IVF oocyte retrieval: prospective evaluation of the type of anesthesia on live birth rate,pain, and patient satisfaction

Purpose

Does the type of anesthesia (paracervical block (PCB) or general anesthesia (GA)) impact live birth rate, pain, and patient satisfaction?

Methods

A non-randomized prospective cohort study was conducted in women treated for IVF. Two groups of patients were prospectively included: the PCB group (n = 234) and the GA group (n = 247). The type of anesthesia was determined by the patients. The primary endpoint was cumulative live birth rate by OR. Secondary endpoints were self-assessment of the patients’ peri-operative abdominal and vaginal pain vs the doctors’ evaluations during PCB, post-operative abdominal and vaginal pain level, and patient satisfaction in both groups. Pain levels were assessed with a numerical rating scale (NRS).

Results

The live birth rate was similar in both groups (19.8% in the GA group vs 20.9% in the PCB group, P = 0.764). During oocyte retrieval in the PCB group, the physicians significantly under-estimated the vaginal pain experienced by the patients (3.04 ± 0.173 for patients vs 2.59 ± 0.113 for surgeons, P = 0.014). Post-operative vaginal and abdominal pain were significantly greater in the PCB group compared to the GA group (2.26 ± 0.159 vs 1.66 ± 0.123, respectively, P = 0.005, and 3.80 ± 0.165 vs 3.00 ± 0.148, respectively, P < 0.001). Patients were more significantly satisfied with GA than with PBC (P < 0.001).

Conclusion

Because the LBR was similar in both groups and patient satisfaction was high, the choice of anesthesia should be decided by the patients.

     

Telomere length is short in PCOS and oral contraceptive does not affect the telomerase activity in granulosa cells of patients with PCOS

Purpose

Our study aimed to investigate the association of telomerase activity (TA) and telomere length (TL) in granulosa cells (GCs) with IVF outcomes of polycystic ovary syndrome (PCOS) patients, and the effects of oral contraceptive pill (OCP) pretreatment on these two parameters.

Methods

One hundred sixty-three infertile women were enrolled and divided into a PCOS group (n = 65) and a non-PCOS group (n = 98). The PCOS group was further divided into an OCP pretreatment group (n = 35) and a non-OCP pretreatment group (n = 30), a TA <0.070 group (n = 34) and a TA ≥0.070 group (n = 31), and a TL <1 group (n = 41) and a TL ≥1 group (n = 24), respectively.

Results

No obvious differences were observed in TA between these groups. The TL was 0.971 in PCOS group and 1.118 in non-PCOS group (P = 0.005). The patients with TL ≥1 accounted for 36.9% in PCOS group and 54.1% in non-PCOS group (P = 0.032). The average duration of infertility for PCOS patients was 5 years in TA <0.070 group and 4 years in TA ≥0.070 group (P = 0.038), and 5 years in TL <1 group and 3 years in TL ≥1 group (P = 0.006), respectively. No obvious differences were observed in IVF outcomes between these groups. No obvious differences were observed in TA, TL, or IVF outcomes between OCP pretreatment group and non-OCP pretreatment group in PCOS patients.

Conclusions

Shorter TL was found in PCOS patients. The TA levels did not change significantly in PCOS patients. PCOS patients with a lower TA level and shorter telomeres had an earlier onset of infertility symptoms. No predictive value was found for TA and TL in terms of embryo quality or IVF outcomes in PCOS patients, and no effect OCP pretreatment was observed on either TA and TL.

     

Human sperm Toll-like receptor 4 (TLR4) mediates acrosome reaction,oxidative stress markers,and sperm parameters in response to bacterial lipopolysaccharide in infertile men

Purpose

To study the role of Toll-like receptor 4 (TLR4) in human spermatozoa and to assess sperm parameters, oxidative stress markers, and acrosome reaction in response to the stimulation of TLR4 by its ligand, the lipopolysaccharide (LPS), as a major endotoxin of Gram-negative bacteria.

Methods

Our study was carried out in 73 sperm samples from patients undergoing semen analysis for couple infertility investigations. The studied patients were divided into three groups: normozoospermic fertile patients (n = 13), patients with abnormal and leukospermic semen (n = 13), and patients with abnormal and non-leukospermic semen (n = 47). TLR4 expression in human spermatozoa was initially analyzed by western blot. Sperm samples were incubated in the presence of LPS (200 ng/ml) for 18 h. Then, sperm motility and vitality were evaluated by microscopic observation and oxidative stress markers as malondialdehyde (MDA) and carbonyl groups (CG) were spectrophotometrically assessed in neat and selected sperm. A triple-stain technique was also performed to evaluate acrosome reaction in 15 sperm samples from infertile patients.

Results

TLR4 expression was confirmed in human spermatozoa with a molecular weight of 69 kDa. In the normozoospermic group, no significant differences in sperm parameters and oxidative stress markers were shown after incubation with LPS in neat and selected sperms. Regarding samples from the non-leukospermic group, LPS reduced spermatozoa motility and vitality rates in selected sperm (P = 0.003; P = 0.004, respectively). A significant increase of MDA and CG levels was also detected (P = 0.01; P = 0.02, respectively). However, only the MDA levels were significantly increased (P = 0.01) in neat LPS-stimulated sperm. The same results were shown within the leukospermic group. The comparison between the two groups, leukospermic and non-leukospermic, in selected sperms showed a more important LPS effect in the leukospermic group significantly on motility and MDA rates (P = 0.006; P = 0.009, respectively). Furthermore, a significant decrease in reacted spermatozoa rate was detected in response to LPS in selected sperm samples from infertile men (P = 0.03).

Conclusions

These findings indicate that human spermatozoa express TLR4 and respond to LPS stimulation with alterations in viability, motility, and the acrosome reaction implicating reactive oxygen species (ROS) production in sperm samples from infertile patients.

     

Obesity results with smaller oocyte in in vitro fertilization/intracytoplasmic sperm injection cycles—a prospective study

Background

Obesity is associated with several fertility disorders. This prospective cohort study was designed to evaluate the effect of body mass index (BMI) (kg/m²) on oocyte diameter and treatment.

Methods

Women undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) were enrolled in the study. They were divided into two groups according to BMI: obese (BMI > 30) and normal weight (BMI < 25). Mature oocytes were evaluated according to total diameter, zona pellucida, and oolema diameters.

Results

A total of 387 oocytes were obtained from the 46 women who participated. Significantly more mature oocytes (M2) were retrieved from normal weight patients compare to obese women (15.1 ± 6.8 vs. 9.7 ± 3.9, respectively, P < 0.001). Oocytes from women in the obese group were significantly smaller than those in the normal weight group, including oocyte diameter (157.9 ± 7.9 vs. 164.3 ± 5.1 μm, P < 0.0001), oolema diameter (110.3 ± 4.5 vs. 113.5 ± 3.5 μm, P < 0.0001), and zona pellucida thickness (17.9 ± 2.6 vs. 19.0 ± 2.4 μm, P < 0.000), respectively. Multivariate logistic regression analysis, including oolema diameter, female age, BMI, number of M2 oocytes, and zona pellucida, was conducted to predict pregnancy. Small oolema diameter in obese patient adversely correlated with pregnancy. Larger oolema diameter was positively associated with the probability of pregnancy in the obese group as well as thinner zona pellucida.

Conclusion

Obesity is associated with smaller oocytes, which adversely affect fertility outcomes.

Trial registration

NIH number NCT01672931

     

Comparison of Mifepristone Followed by Misoprostol with Misoprostol Alone for Treatment of Early Pregnancy Failure: A Randomized Double-Blind Placebo-Controlled Trial

Objective

To compare the efficacy and safety of mifepristone followed by misoprostol with misoprostol alone in the management of early pregnancy failure (EPF).

Study Design

A randomized double-blind placebo-controlled clinical trial.

Methods

Ninety-two women with EPF ≤12 weeks were recruited and randomly allocated to receive either mifepristone 200 mg (n = 46) or placebo (n = 46). Forty-eight hours later, patients in both the groups were given 800 µg misoprostol per-vaginum. If no expulsion occurred within 4 h, repeat doses of 400 µg misoprostol were given orally at 3-hourly interval to a maximum of 2 doses in women ≤9 weeks by scan and 4 doses in women >9 weeks by scan.

Results

Pre-treatment of misoprostol with mifepristone significantly increased the complete abortion rate (86.7 vs. 57.8%, p = 0.009) and, hence, reduced the need for surgical evacuation (13.3 vs. 42.2%, p = 0.002), induction to expulsion interval (4.74 ± 2.24 vs. 8.03 ± 2.77 h, p = 0.000), mean number of additional doses of misoprostol required (0.68 vs. 1.91, p = 0.000), and side effects.

Conclusion

Use of mifepristone prior to misoprostol in EPF significantly improves the efficacy and reduces the side effects of misoprostol alone.

     

Effects of reduced seminal enzymatic antioxidants on sperm DNA fragmentation and semen quality of Tunisian infertile men

Purpose

To evaluate levels of sperm DNA fragmentation and enzymatic antioxidant status in seminal plasma of Tunisian fertile and infertile men in order to assess the effects of seminal oxidative stress on sperm DNA integrity and semen quality.

Methods

Semen samples from 100 infertile patients (40 oligoasthenoteratozoospermics, 31 teratozoospermics and 29 asthenozoospermics) and 50 fertile men (controls) were analyzed for DNA fragmentation by TUNEL assay and biochemical parameters. Seminal antioxidant activities (Superoxide dismutase, Glutathione peroxidase and Catalase) and malondialdehyde concentrations were measured spectrophotometrically.

Results

Sperm DNA fragmentation and malondialdehyde levels in infertile groups were more elevated than controls. Nevertheless, the activities of the antioxidant enzymes were significantly lower in abnormal groups compared to normozoospermics. Sperm DNA fragmentation was closely and positively correlated to malondialdehyde levels (r?=?0.37, P?=?0.008); meanwhile, reduced seminal antioxidant profile was negatively associated to sperm DNA fragmentation. Interestingly, we noted also that sperm DNA fragmentation was negatively correlated to sperm motility (r?=??0.54, P?<?0.001) and positively associated to the abnormal sperm morphology (r?=?0.57, P?=?0.002).

Conclusions

This report revealed that increased sperm DNA fragmentation can be due to the impaired seminal enzymatic antioxidant profile and increased Lipid peroxidation. Our results sustain that the evaluation of sperm DNA fragmentation and seminal oxidative biomarkers in infertile men is recommended as a consistent prognostic tool for male infertility assessment.

     

Sperm preparation after freezing improves motile sperm count,motility, and viability in frozen-thawed sperm compared with sperm preparation before freezing-thawing process

Purpose

The aim of this study is to evaluate which cryopreservation protocol, freezing before or after swim-up, optimizes cryopreservation outcomes in terms of motile sperm count, motility, morphology, and viability, and also to establish whether sperm viability could be assessed based on sperm motility.

Methods

Fifty-three fresh and 53 swim-up prepared samples were considered for the first experiment. In parallel, total motility evaluation by CASA system (computer-assisted sperm analyzer) and hypoosmotic swelling test (HOS-test) was performed in each sample to compare the viability results of both methods. In the second experiment, 21 normozoospermic semen samples and 20 semen samples from male factor patients were included. After fresh ejaculate evaluation, the semen sample of each patient was divided into two aliquots, one of them was frozen before swim-up and the other was frozen after swim-up. Motility, sperm count, morphology, and viability were evaluated after thawing.

Results

A linear regression model allows prediction of HOS-test viability results based on total motility: HOS?=?1.38?+?0.97?·?TM (R ² = 99.10, residual mean squares = 9.51). Freezing before sperm selection leads to higher total and progressive motility, total motile sperm count, and viability rates than when sperm selection is performed before freezing (P < 0.005 in all cases). In fact, sperm selection prior to freezing reaches critical values when subfertile patients are considered.

Conclusions

To conclude, total motility evaluation can predict HOS-test viability results, resulting in a more objective and less time-consuming method to assess viability. In addition, sperm freezing prior to swim-up selection must be considered in order to achieve better outcomes after thawing, especially in patients presenting poor sperm baseline.

     

Study of Effect of Vitamin D Supplementation on the Clinical,Hormonal and Metabolic Profile of the PCOS Women

Introduction

Insulin resistance is one of the most common features of polycystic ovary syndrome, and some studies suggest that vitamin D deficiency may have role in insulin resistance.

Objective

To study the effect of vitamin D supplementation on the clinical, hormonal and metabolic profile of the PCOS women.

Study Design

Randomized, placebo-controlled, interventional, double-blind study.

Materials and Methods

PCOS women were evaluated and enrolled after considering inclusion and exclusion criteria. They were randomized by block randomization with sealed envelope system done in two groups. In the study group (n = 25), patients were supplemented with vitamin D 60,000 IU weekly for 12 weeks, whereas control group (n = 25) was given placebo weekly for the same period. Both the groups were compared pre- and post-supplementation for variables like clinical profile, biochemical profile and metabolic profile. Statistical analysis was performed by the SPSS program for Windows, version 10.1 (SPSS, Chicago, IL).

Result

In the study (n = 50), PCOS patients were enrolled; 34 patients (68%) were vitamin D deficient (≤20 ng/ml) out of which 10 patients (29%) were severely deficient (<10 ng/ml). Twelve patients (24%) were vitamin D insufficient showing high prevalence of vitamin D deficiency in the PCOS women. The difference in mean serum fasting glucose pre- and post-supplementation of vitamin D in study group was found to be statistically significant with p value of 0.041. There was significant difference seen in insulin resistance (IR) (2.38 ± 4.88–1.00 ± 0.58, p = 0.003), serum fasting insulin (10.34 ± 20.00–5.00 ± 3.25, p = 0.021), and increase in insulin sensitivity determined by QUICKI (0.37 ± 0.04–0.394 ± 0.009, p = 0.001) after supplementation with vitamin D.

Conclusion

The study concluded that there was a beneficial effect of vitamin D supplementation on ovulatory dysfunctions and blood pressure. Post-supplementation, there were decrease in insulin resistance and increase in insulin sensitivity. In the study decreased serum fasting insulin level and fasting blood sugar after vitamin D supplementation suggest underlying role of vitamin D in glucose homeostasis.

     

GnRH antagonist administered twice the day before hCG trigger combined with a step-down protocol may prevent OHSS in IVF/ICSI antagonist cycles at risk for OHSS without affecting the reproductive outcomes: a prospective randomized control trial

Purpose

The purpose this study is to investigate whether a double antagonist dose (0.25 mg/12 h) administered the day before hCG trigger is effective in preventing ovarian hyperstimulation syndrome (OHSS) in GnRH antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles at risk for OHSS.

Methods

This is a prospective randomized control study, conducted from November 2012 to January 2016. A total of 194 patients undergoing a IVF/ICSI GnRH antagonist cycle that were at risk of OHSS and chose to proceed with embryo transfer and avoid cycle cancellation or embryo cryopreservation were allocated into two groups. The inclusion criteria consisted of a rapid rise of oestradiol ≥ 3500 pg/ml combined with ≥ 18 follicles > 11 mm in diameter without any mature follicle > 16 mm, in any day of stimulation. Overall, 97 patients (intervention group A) received a double dose of GnRH antagonist (0.25 mg/12 h) the day before hCG while 97 patients (control group B) did not. Recombinant FSH administration was tapered to 100 IU/24 h the day of the allocation in both groups.

Results

Incidence of early-onset moderate/severe OHSS was significantly lower in intervention group A compared to control group B (0 vs 12.37%, P < 0.001). Clinical pregnancy rate per cycle (50.52 vs 42.27%, P = 0.249) was not significantly different between the two groups. Oestradiol (3263.471 ± 1271.53 vs 5233 ± 1425.17, P < 0.001), progesterone (0.93 ± 0.12 vs 1.29 ± 0.14, P < 0.001) and luteinizing hormone (1.42 ± 0.31 vs 1.91 ± 0.33, P < 0.001) were significantly lower in group A the day of the hCG triggering.

Conclusion

The administration of a rescue double GnRH antagonist dose the day before hCG trigger may represent a safe alternative preventive strategy for early OHSS without affecting the reproductive outcomes.

Trial registration number

ISRCTN02750360

     

A new method to process testicular sperm: combining enzymatic digestion,accumulation of spermatozoa,and stimulation of motility

Purpose

In azoospermia processing of the TESE material often results in a sample of reduced purity. This prospective study was set up to clarify whether a combination of enzymatic digestion, density gradient centrifugation and stimulation of motility (where indicated) is a feasible option in TESE patients.

Methods

A total of 63 samples (showing spermatozoa) were processed by the present tripartite processing method. The resulting sperm sample of high purity was directly used for ICSI and subsequent cryopreservation when quality of the accumulated sperm sample allowed for it (n = 39 cycles).

Results

Compared to the control group blastocyst formation rate in the present tripartite processing technique was significantly (P < 0.01) higher (55.2 vs. 43.7 %). Fertilization rates differed significantly (P < 0.001) between cases in which motile sperm could be used (58.4 %) compared to ICSI with immotile sperm (45.0 %). Clinical pregnancy rate per transfer was 40.0 % (24/60) using fresh and 21.6 % (8/37) with cryopreserved TESE material. The calculated live birth rates were 31.7 and 21.6 %, respectively. Thirty-five healthy children were born.

Conclusions

A comparison with a control group suggests that the present approach using standardized ready-to-use products is efficient and reliable. Presumably healthy live births further indicate the safety of the procedure.

     

Is early embryo development as observed by time-lapse microscopy dependent on whether fresh or frozen sperm was used for ICSI? A cohort study

Purpose

The aim of this study was to compare timings of key events of embryo development from those originating from either fresh or cryopreserved ejaculate sperm using time-lapse technology.

Methods

In this retrospective observational cohort study, time-lapse technology was used to monitor 1927 embryos from 234 women undergoing intracytoplasmic sperm injection (ICSI) and utilizing either fresh (n = 172 cycles) or cryopreserved ejaculate sperm (n = 62 cycles) for insemination were included in the study. Key developmental events as described in time-lapse were compared with the use of generalized estimating equations (GEE) to adjust for any auto-correlation between the observations. In addition, multivariable logit regression models were used to account for any known baseline differences between the two groups.

Results

There were no differences in conventional embryo development such as number of 8-cell embryos by 72 h (p = 0.359), the number of blastocysts by 120 h (p = 0.417), and the number of top quality blastocysts (p = 0.956) between the two groups compared. There were no statistical differences in the timings of any of the key embryo developmental events (PN_t1, NEBD, cytokinesis, t2, t3, t4, t5, t6, t7, t8, tM, tSB, tEB, tHB, s1, s2, s3, cc2, and cc3) when either fresh or cryopreserved ejaculate sperm was used for ICSI. This was also confirmed with conventional morphological assessment.

Conclusions

This observational cohort study has shown that there are no differences in the morphokinetic parameters of early embryo development when either fresh or frozen ejaculate sperm are used for ICSI insemination.

     

Outcomes of intracytoplasmic sperm injection using the zona pellucida-bound sperm or manually selected sperm

Purpose

Zona pellucida (ZP)-bound sperm used for intracytoplasmic sperm injection (ICSI) enhances embryo quality, implantation, and clinical pregnancy rates. This study aimed to assess the pregnancy outcomes and clinical significance of ICSI with ZP-bound sperm.

Method

A total of 84 infertile couples who underwent cycles of ICSI following failed in vitro fertilization between June 2012 and February 2014 were enrolled and randomized (1:1): in the treatment group, ICSI was performed using ZP-bound sperm; in the control group, ICSI was performed in a standard manner. Rates of fertilization, cleavage, high-quality embryos, and clinical pregnancy were compared between the two groups.

Results

There were no significant differences in age, infertile period, gonadotrophin dose, number of metaphase II oocytes, and number of embryo transfers between the two groups (P?>?0.05). The clinical pregnancy rate was higher in the treatment group than in the control group, but without statistical significance (60.5 vs. 47.6 %, P?>?0.05). No significant differences in the rates of fertilization and cleavage were observed (83.0 vs. 81.6 %, and 96.3 vs. 96.5 %, both P?>?0.05), but higher rates of high-quality embryos and useable embryos were observed with ZP-bound sperm compared with controls (66.1 vs. 50.8 % and 76.0 vs. 66.3 %, both P?<?0.05).

Conclusions

ICSI using ZP-bound sperm might increase the embryo quality and number of useable embryos, possibly improving the clinical pregnancy outcome of ICSI.

     

WBP2NL/PAWP mRNA and protein expression in sperm cells are not related to semen parameters,fertilization rate,or reproductive outcome

Purpose

WBP2NL/PAWP, a protein found in the post-acrosomal region of mammalian spermatozoa, has been proposed as a sperm-borne oocyte-activating factor (SOAF) contributing to Ca²⁺ release within the oocyte and subsequent fertilization and embryo development. However, its relevance as either a diagnostic or a prognostic marker of fertilization failure has been questioned in the recent literature. We analyzed WBP2NL/PAWP gene and protein expression level and localization in patients without previous intracytoplasmic sperm injection (ICSI) cycles in order to assess its association with both sperm characteristics and ability to fertilize.

Methods

Raw frozen-thawed semen samples from 33 couples referred for oocyte donation were included in the study during 2015. Relative protein expression versus α-tubulin (western blot, WB), proportion of post-acrosomal WBP2NL/PAWP-positive spermatozoa over the total number of sperm cells (immunofluorescence), and WBP2NL/PAWP gene expression (RT-qPCR) were analyzed and correlated with semen analysis parameters (number, motility, and morphology) and with reproductive outcomes.

Results

WBP2NL/PAWP protein was expressed in all samples with high variability: relative protein expression (1.77 ± 0.8, range [0.4–3.7]), proportion of positive cells (49.6% ± 16.1, range [22–89]), and relative gene expression (7.3 ± 8.2). No significant correlation (R ² < 0.1) was found between gene and protein expression, neither between WBP2NL/PAWP gene or protein expression, and fertilization rate or other reproductive outcomes (i.e., pregnancy). In contrast, we found significant correlation between sperm morphology and WBP2NL/PAWP semiquantitative analysis in WB (r = ?0.42, p < 0.05) and for sperm motility and WBP2NL/PAWP expression in IF (r = 0.52, p < 0.05).

Conclusion

Taken into account that WBP2NL/PAWP gene and protein levels and distribution did not correlate with fertilization rates, this study questions the interest of WBP2NL/PAWP protein and gene expression analysis in sperm cells as a prognostic factor for the outcome of ICSI cycles. Larger studies focusing on WBP2NL/PAWP protein and gene expression are needed in order to evaluate the role of WBP2NL/PAWP as a prognostic factor for ART.

     

Comparison of effects of thawing entire donor sperm vial vs. partial thawing (shaving) on sperm quality

Purpose

Partial thawing of a vial of cryopreserved sperm (shaving) is sometimes applied as a measure to preserve sperm for further use, particularly in cases of very restricted sperm quantity. However, mechanical violence may disrupt the sperm-wall and lead to impaired in-vitro fertilization (IVF) outcomes.

Material and methods

In a retrospective case-control study at a tertiary, university-affiliated medical center, we compared the IVF/intracytoplasmic sperm injection (ICSI) outcomes of patients who used donor sperm following partial thawing (shaving) of the vial of cryopreserved sperm (n?=?99) to a control group consisting of patients for whom the vial of sperm was completely thawed before use (n?=?99).

Results

While no differences were observed in the rates of oocyte fertilization, the mean number of top-quality embryos (TQE) was significantly lower in the shaving group than in the complete thawing group (1.33?±?0.17 vs. 1.87?±?0.17, p?<?0.02). Experimental analysis of aliquots from the same donors revealed significantly reduced motility in sperm samples that were shaved vs. fully thawed (6.5 vs. 37.1%, p?<?0.001).

Conclusions

In cases in which available cryopreserved sperm samples are limited, shaving of the vial without thawing can be used but with caution and only when absolutely necessary. Further, large prospective studies are needed to better clarify whether there is post-thawing sperm damage and to compare IVF outcomes after these two thawing methods.

     

Neonatal outcomes among twins stratified by method of conception: secondary analysis of maternal fetal medicine (MFMU) network database

Purpose

To investigate whether twin pregnancies conceived by different forms of fertility treatments are associated with adverse neonatal outcomes and to examine the difference in maternal and obstetrical characteristics between patients.

Methods

Our study was a retrospective analysis of twin pregnancies conceived by fertility treatments from a prospectively collected database. Treatments were stratified into two groups: group 1 (ART) consisted of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and group 2 (non-ART) included intrauterine insemination (IUI) and ovulation induction (OI). Composite neonatal morbidity included respiratory distress syndrome, intraventricular hemorrhage, leukomalacia, chronic lung disease, and death prior to discharge.

Results

There were 460 neonates in our study; among them, 67% (n?=?310) were in group 1, and 33% (n?=?150) in group 2. Group 1 patients were more likely to be older (p?=?0.004), nulliparous (p?=?0.01), delivered twins with lower birth weights (2278 g?±?605 vs. 2427?±?519, p?=?0.009), and had more deliveries <?32 weeks gestation (p?=?0.001). In multivariable Poisson regression model, only neonatal intensive care unit admission rate was increased for group 1 twins (aRR?=?1.27, 95% CI 1.003–1.60).

Conclusions

After adjusting for confounders, twins conceived via ART compared to non-ART had similar neonatal outcomes. These data can help when counseling this patient population and assist in planning larger prospective cohorts.

     

Are blastocyst aneuploidy rates different between fertile and infertile populations?

Purpose

This study aimed to determine if patients with infertility or recurrent pregnancy loss have higher rates of embryo aneuploidy than fertile controls.

Methods

This was a retrospective review of all pre-implantation genetic screening (PGS) cases processed by a single reference lab prior to March 2014 after a blastocyst biopsy. Cases were excluded if no indication for PGS was designated or patients were translocation carriers. The fertile control group consisted of patients undergoing IVF with PGS for sex selection only. The comparison cohorts included those with recurrent pregnancy loss, male factor infertility, unexplained infertility, prior failed IVF, or previous aneuploid conceptions. A quasi-binomial regression model was used to assess the relationship between the dependent variable, aneuploidy rate and the independent variables, maternal age and reason for PGS. A quasi-Poisson regression model was used to evaluate the relationship between similar independent variables and the number of blastocyst biopsies per case.

Results

The initial study population consisted of 3378 IVF-PGS cycles and 18,387 analyzed trophectoderm samples. Controlling for maternal age, we observed an increased rate of aneuploidy among patients with recurrent pregnancy loss (OR 1.330, p < 0.001), prior aneuploid pregnancy (OR 1.439, p < 0.001), or previous failed IVF cycles (OR 1.356, p = 0.0012) compared to fertile controls. Patients with unexplained and male factor infertility did not have a significantly different aneuploidy rate than controls (p > 0.05). The increase in aneuploidy in patients with RPL and prior IVF failure was driven by both an increase in meiotic (OR 1.488 and 1.508, p < 0.05) and mitotic errors (1.269 and 1.393, p < 0.05) relative to fertile controls, while patients with prior aneuploid pregnancies had only an increased risk of meiotic error aneuploidies (OR 1.650, p < 0.05).

Conclusions

Patients with recurrent pregnancy loss, previous IVF failures, and prior aneuploid pregnancies have a significantly higher, age-independent, aneuploidy rate compared to patients without infertility.