Acceptability and Feasibility of Initiating a Low Fat Eating Plan in Reproductive Aged Women with Obesity.

Adverse effects of obesity on reproduction are believed in part due to diet related factors leading to hyperlipidemia and hyperinsulinemia. It is unknown whether administration of a low fat eating plan, regardless of weight loss, will improve reproductive axis function in women with obesity. To develop an acceptable and feasible low fat eating plan for a diverse group of reproductive aged women with obesity. Focus groups to determine preferences and barriers to a planned dietary intervention providing very low fat (22% daily calories from fat) eucaloric food to control fat exposure, but not cause weight loss. Logistics of the intervention and monitoring over three menstrual cycles were discussed. Eighteen women enrolled into 4 different focus groups both live and video, 2 at the University of Colorado and 2 at the Morehouse School of Medicine. All participants expressed interest in implementing a low fat dietary intervention and were further interested in instruction on how to maintain healthy eating habits for future fertility. Provision of ethnically appropriate foods, social support to avoid lapses, and tasty alternatives to high fat foods were considered ideal aspects of a feasible intervention. Incentives and graduated compensation for adherence were considered desirable features. Women with obesity are interested in implementing dietary interventions that may improve their health and fertility. Given the diversity of responses based upon the demographics of our sample, it is important to assess geographical and cultural preferences prior to implementing of a dietary strategy.

Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking.

OBJECTIVE: To evaluate the efficiency of oocyte donation cycles using egg "cryo-banking." DESIGN: Study conditions for vitrified/warmed oocytes for 20 non-autologous recipients (from 10 donors) were set prospectively, and outcomes of it were later compared retrospectively to nine fresh donations cycles. SETTING: Private assisted reproductive technology program. PATIENT(S): Ten donors and 20 infertile recipients. INTERVENTION(S): Oocytes were vitrified 3 to 4 hours after collection and cryo-stored. Intracytoplasmic sperm injection was performed 3 hours after warming, and embryos were in vitro cultured for 5 days. Two or three blastocysts were transferred per patient. MAIN OUTCOME MEASURE(S): Oocyte survival, fertilization, development, clinical pregnancy, and implantation rates. RESULT(S): A total of 153 oocytes were warmed and 134 survived. A total of 117 fertilized and 68% developed to blastocyst stage. A total of 47 embryos were transferred (2.35 embryos per recipient) and 26 implanted. Fifteen patients achieved ongoing pregnancies initially, and two additional pregnancies were obtained after transfer of supernumerary vitrified/warmed embryos. Nine of the 10 donors from the current study had previous fresh donations cycles from where seven clinical pregnancies were established in nine recipients, providing the base for comparison. CONCLUSION(S): Oocyte donation using vitrified/warmed oocytes can provide high pregnancy and implantation rates, and thus can be considered as efficient treatment procedure with additional benefits to recipients.

Comparison of ICSI and conventional IVF in patients with increased oocyte immaturity.

Using sibling oocytes, the objective of this study was to compare the intracytoplasmic sperm injection (ICSI) fertilization rates to those achieved with conventional IVF in patients with high rates of oocyte immaturity. This study was observational in nature, and included 91 patients who were treated using split insemination techniques. The fertilization rates for the ICSI group and the IVF group were 41.1 +/- 15.0% and 53.2 +/- 19.8%, respectively (P <: 0.0001). There was no significant difference in day-3 embryo quality between the two groups. There was a significantly higher number of embryos frozen in the IVF group than in the ICSI group: 357 (84.8%) and 297 (76.7%), respectively (P = 0.037). Furthermore, the number of embryos either transferred or frozen was significantly higher in the IVF group than the ICSI group: 459 of 1173 (39.1%) and 385 of 1268 (30.4%), respectively (P < 0.0001). These data indicate that conventional IVF results in a higher fertilization rate than ICSI. Furthermore, IVF provided more embryos available for transfer or cryopreservation when compared with ICSI, thereby optimizing the patient's cycle.

Influence of the preimplantation embryo development (Ped) gene on embryonic platelet-activating factor (PAF) levels.

PURPOSE: A major gene responsible for the control of preimplantation cleavage rate is the Ped gene, the product of which is the Qa-2 protein. Fast, but not slow developing mouse embryos express the Qa-2 protein. Platelet-activating factor (PAF) is a novel and potent signaling phospholipid that has unique pleiotropic properties in addition to platelet activation. PAF plays a significant role in virtually every reproductive event, including ovulation, fertilization, implantation, and parturition. The role of the Ped gene in PAF production by preimplantation embryos is yet to be established. The presence of this gene provides embryos with a reproductive advantage over those that are Ped negative, and may also serve as a regulator of PAF synthesis. The study hypothesis is that the amount of PAF produced is dependent upon the presence or absence of the Ped gene. METHODS: B6.K1 (Ped negative) and B6.K2 (Ped positive) mouse embryo-conditioned culture media were assayed for PAF content by a PAF-specific radioimmunoassay. RESULTS: There was a significant (p < 0.001) difference in blastocyst development rates between the Ped+ B6.K2 (61.0%) and the Ped- B6.K1 (25.3%) embryo culture groups. There was a significant difference (p < 0.05) in PAF production between the Ped+ B6.K2 (4.70+/-0.46 pmol per embryo) embryo culture group and the Ped- B6.K1 (10.02+/-3.49 pmol per embryo) embryo group. The B6.K1 (Ped-) embryo group produced >2x more PAF than did the B6.K2 (Ped+) group. CONCLUSIONS: The Ped gene plays a role in PAF production and release in preimplantation stage embryos. The use of two mouse identical strains, except for the Ped gene, show that its presence is associated with an increase in developmental potential. Embryos where the Ped gene was absent produced significantly higher levels of PAF, which may aid in their survival.

Comparison of bovine- and recombinant human-derived hyaluronidase with regard to fertilization rates and embryo morphology in a sibling oocyte model: a prospective, blinded, randomized study.

The objective of the present study was to compare a traditionally used bovine-derived hyaluronidase (Hyase) with the newly developed recombinant human-derived enzyme product (Cumulase) in intracytoplasmic sperm injection (ICSI) procedures using a sibling oocyte model in a prospective randomized design. The results of the study demonstrate that Cumulase is safe and effective in an ICSI treatment program and can provide comparable if not improved parameters, including fertilization and embryo developmental rates.

Platelet-activating factor acetylhydrolase activity affects sperm motility and serves as a decapacitation factor.

OBJECTIVE: To determine the relationship between platelet-activating factor acetylhydrolase (PAFah) content in semen and sperm motility. DESIGN: The PAFah levels in semen were measured and correlated with sperm motility. SETTING: Clinical laboratory in a private assistant reproductive technology clinic. PATIENT(S): Three hundred and twelve men seeking diagnosis and treatment of infertility. INTERVENTION(S): Semen samples were collected from 312 healthy mature men seeking infertility treatment. Sperm motility and PAFah activity were measured in seminal plasma. Data was analyzed by Student's t test and regression analysis. MAIN OUTCOME MEASURE(S): PAFah activity and sperm motility. RESULT(S): Seminal PAFah content ranged from a low of 179 IU/L to a high of 2,457 IU/L. The overall mean PAFah content in semen was 780.59 IU/L. Linear regression analysis revealed a significant (R2 = 0.655) and negative relationship between PAFah content in semen and sperm motility. Semen specimens with high percent motility (> or = 50%) had significantly lower PAFah concentrations (442.03 +/- 14.37 IU/L) than those with the lower percent sperm motility (< 50%) (882.16 +/- 18.45 IU/L). CONCLUSION(S): The data confirm the presence of PAFah in human semen and that activity is significantly and negatively correlated with sperm motility. The PAFah is proven to be a candidate for sperm decapacitation factors, whereas PAF is qualified to be a candidate for sperm capacitation factors.

Impact of body mass index values on sperm quantity and quality.

Body mass index (BMI) has been demonstrated to affect female fertility; however, little information is available on the impact of BMI on male fertility or semen parameters. Therefore, the study objective was to determine the relationship between BMI and semen parameters, including sperm chromatin integrity. We analyzed data on semen samples from 520 men who were grouped based upon calculated BMI values (normal, 20-24 kg/m(2); overweight, 25-30 kg/m(2); obese, >30 kg/m(2)). The data collected included patient height and weight, semen volume, sperm concentration, percent sperm motility, percent sperm morphology (normal forms), and sperm chromatin integrity (DNA fragmentation index [DFI]). Data were analyzed by regression analysis and analysis of variance (ANOVA) with Tukey's test for multiple pairwise comparisons. The overall BMI mean (+/-SEM) was 27.5 (+/-0.49) kg/m(2). Linear regression revealed a significant (P < .05) and negative relationship between BMI and the total number of normal-motile sperm cells. ANOVA revealed a significant difference (P < .05) in the total number of normal-motile sperm cells among the different BMI groups. The number of normal-motile sperm cells per BMI group was as follows: normal, 18.6 x 10(6); overweight, 3.6 x 10(6); and obese, (0.7) x 10(6). All multiple pairwise comparisons were found to be significantly (P < .05) different. The overall DFI mean (+/-SEM) was 24.7 (+/-2.57). Linear regression revealed a significant (P < .05) and positive relation between BMI and DFI. Men presenting with a BMI greater than 25 kg/m(2) have fewer chromatin-intact normal-motile sperm cells per ejaculate. Therefore, to ensure maximum fertility potential, patients may be advised to reduce body weight.

Quantitative DNA perturbations of p53 in endometriosis: analysis of American and Icelandic cases.

OBJECTIVE: To investigate quantitative aberrations involving p53 copy numbers in eutopic endometrial and endometriotic tissue from two populations. DESIGN: Comparative analysis of normal and diseased tissue. SETTING: Tissue specimens collected in Iceland and USA. PATIENT(S): Subjects with moderate/severe endometriosis (Iceland, n = 26; USA, n = 45). Paraffin-embedded tissue from 19 matched Icelandic cases and seven unaffected controls. American cases were fresh surgical tissue from 17 matched cases and 28 unaffected controls. DNA isolation and real-time polymerase chain reaction (PCR) with TaqMan assay were performed. MAIN OUTCOME MEASURE(S): The frequency of p53 loss and/or gain based on quantitative differences for copy numbers of p53 located on chromosome (17p) and GAPDH on a control locus (chromosome 12p). RESULT(S): Among American cases, significant p53 gain (n = 13) or loss (n = 4) was observed in 17 of 21 cases. In Icelandic cases this was not seen to the same degree. Mean normalized p53 values were 3.46 and 1.16 copies per reaction, respectively. Significant differences were observed between normalized p53 in the control blood and affected tissue for the American and Icelandic cases compared to standard GAPDH control but not in normal Icelandic and American endometrium. CONCLUSION(S): The results continue to support a role for nonrandom somatic p53 locus alterations in the pathogenesis of late or severe-stage endometriosis. Differences between Icelandic and American subjects have implications for generalization of genome-wide approaches.

Ganirelix acetate use in normal- and poor-prognosis patients and the impact of estradiol patterns.

OBJECTIVE: To evaluate cycle outcomes in patients with either poor or normal prognosis undergoing IVF treatment with a GnRH antagonist (ganirelix acetate) for LH suppression. DESIGN: Nonrandomized, noncontrolled, retrospective review. PATIENT(S): 204 patients, aged 23-41 years, undergoing IVF. INTERVENTION(S): Patients completed 225 consecutive cycles of IVF with a GnRH antagonist (Antagon; Organon, Roseland, NJ) for LH surge prevention. Sixty cycles were conducted in patients with a known poor prognosis, whereas 165 were conducted in patients with a normal IVF prognosis. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR), for the series as a whole and according to prognosis, and serum E2 patterns. RESULT(S): The PR per initiated cycle for the series as a whole was 33.3%. The pregnancy rate was 42.1% per ET for the entire series, with a cycle cancellation rate of 21%. When evaluated by prognosis, the poor-prognosis patients had PRs of 8.3% per attempt and 15% per transfer, whereas the normal-prognosis patients had PRs of 40% per attempt and 45% per transfer. Pregnancy rate did not vary by E2 pattern (drop, plateau, or rise). Oral contraceptive pretreatment was noted to be associated with high cancellation rates in the group of known poor responders, whereas for the group as a whole, cycle outcome was unaffected by the use of oral contraceptives. CONCLUSION(S): Use of GnRH antagonists in patients with an a priori poor IVF prognosis results in predictably poor outcomes. Patients without factors predicting poor outcome have acceptable PRs. The pattern of E2 rise immediately after initiation of GnRH antagonists does not predict cycle outcome. Oral contraceptives can be successfully used to schedule antagonist-based IVF cycles but might increase the risk of cycle cancellation in some patient populations.

The significance of platelet-activating factor and fertility in the male primate: a review.

Since its discovery nearly 30 years ago platelet-activating factor (PAF) has emerged as one of the more important lipid mediators known. PAF (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) exists endogenously as a mixture of molecular species with structural variants of the alkyl moiety. PAF is a novel potent signaling phospholipid that has unique pleiotropic biological properties in addition to platelet activation. PAF also plays a significant role in reproduction and is present in the sperm of a number of primate species. PAF content in squirrel monkey sperm is significantly higher during the breeding season than the non-breeding season. PAF content in rhesus sperm has a significant relationship with sperm motility. PAF content in human sperm has a positive correlation with seminal parameters and pregnancy outcomes. The enzymes (lyso-PAF-acetyltransferase and PAF-acetylhydrolase) necessary for PAF activation and deactivation are present in primate sperm. PAF-acetylhydrolase may act as a "decapacitation factor". Removal of this enzyme during capacitation promotes PAF synthesis increasing primate motility and fertilization. PAF also plays a significant role in the fertilization process, enhancing the fertilization rates of oocytes. Enhanced embryo development has also been reported in oocytes fertilized with PAF-treated sperm. Exogenous PAF will also significantly improve primate artificial insemination pregnancy outcomes. PAF antagonists inhibit sperm motility, acrosome reaction, and fertilization thus suggesting the presence of receptors for PAF. The PAF-receptor is present on primate sperm, with altered transcript levels and distribution patterns on abnormal cells. Whereas, the exact mechanism of PAF in sperm function and reproduction is uncertain, its importance in normal primate fertility is substantial.

Exposure of preimplantation embryos to platelet-activating factor increases birth rate.

PROBLEM: Platelet-activating factor (PAF) plays a significant role in fertility. Preimplantation stage embryos produce PAF (ePAF) which is required for development. PAF's mechanism of action is receptor-mediated and its presence has been reported in the developing mouse and human embryo. Exposure of preimplantation stage mouse embryos results in higher implantation rates. However, the effect of such treatment on live-birth rates and birth weights has not been reported. Therefore, the objective the study was to determine the effect of exposing preimplantation mouse embryos to PAF on subsequent birth rate and weight. DESIGN: Two-cell stage preimplantation stage mouse embryos exposed to PAF (10(-7) M) for 15 min prior to intraoviductal transfer. METHODS: Preimplantation stage embryos were recovered from eCG/hCG primed BDF1 female mice. Embryos were exposed to synthetic PAF (10(-7) M) for 15 min. PAF-treated embryos were transferred to the oviducts of pseudopregnant female CD-1 female mice. Superovulated and cultured BDF1 embryos not treated with PAF served as in vitro controls and naturally ovulated embryos with no collection/culture served as in vivo controls. Embryos were permitted to develop to term (18-21 days). The number of pups born per litter and litter weights subsequently were recorded. RESULTS: A total of 160 BDF1 mouse embryos were collected, treated, and transferred (20 per CD-1 recipient) as described. There was a significant (P < 0.05) increase in the number of pups born to the PAF treatment group (56/80; 70%) as compared to the control group (44/80; 55%). There was also a significant difference (P < 0.05) in litter birth weights between the PAF (1.31 g/litter) and controls groups (1.25 g/litter). There was a significant difference (P < 0.05) in birth weights between the PAF treatment group and the in vivo group (1.51 g/litter). There was a significant difference in birth weights between the in vitro-control and in vivo groups (1.51 g/litter). There were no observational malformaties to pups born in any group. CONCLUSIONS: Brief exposure of preimplantation stage embryos to PAF will result in a significant increase of delivery rates (pups/litter) as well as birth weights. However, the increase of birth weight was significantly below that found naturally. Additional studies are warranted to elucidate the mechanism of PAF's action in the preimplantation stage embryo and subsequent uterine development.

Platelet-activating factor significantly enhances intrauterine insemination pregnancy rates in non-male factor infertility.

OBJECTIVE: To determine the efficacy of treating semen specimens with platelet-activating factor (PAF) before IUI. DESIGN: Prospective randomized double-blinded study of PAF treatment of sperm for patients with a history of infertility undergoing IUI. SETTING: Private infertility center. INTERVENTION(S): Patients had ovulation induction therapy with clomiphene citrate (CC) or gonadotropin, two IUIs per month with PAF treatment. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): There was a significant difference in IUI pregnancy rates per cycle between control (10/56; 17.9%) and PAF (14/47; 29.8%) treatment groups in the normal male study arm. There was a significant difference in cumulative IUI pregnancy rates between control (10/35; 28.6%) and PAF (14/26; 53.9%) patient groups in the normal male study arm. There was no significant difference in IUI pregnancy rates per cycle between control (12/124; 9.7%) and PAF (14/119; 11.8%) treatment groups in the male factor study arm. There was no significant difference in cumulative IUI pregnancy rates between control (12/46; 26.1%) and PAF (14/38; 36.8%) patient groups in the male factor study arm. There was a significant difference in overall cumulative IUI pregnancy rates between control (21/81; 25.9%) and PAF (27/64; 42.2%) patient groups. CONCLUSION(S): The inclusion of PAF into the IUI sperm wash procedure significantly improves pregnancy rates. However, the significant improvement can only be shown to affect men presenting with normal semen parameters.

Fertilization potential of human sperm is correlated with endogenous platelet-activating factor content.

PURPOSE: Platelet-activating factor (PAF) is a potent signaling phospholipid that is found in mammalian sperm and has a positive correlation with fertility. Whereas PAF is present in human sperm, there are no relational reports on its content and the cells fertilization potential. Therefore, the study objective was to determine if PAF content in capacitated-induced sperm is related to fertilization potential as determined by the sperm penetration assay (SPA). METHODS: Endogenous sperm lipids were measured for PAF content by a specific radioimmunoassay following insemination of zona pellucida-free hamster ova. Data were analyzed by regression analysis and Student's t test. RESULTS: Regression analysis revealed a positive and significant relation (R2 = 0.806; P < 0.05) between PAF content in human sperm and SPA outcome (pass: > or = 5.0; fail: < 5.0, penetrations/ova). Patients that passed (22.61 +/- 5.21 picomoles/10(6)) the SPA had significantly (P < 0.01) higher PAF levels in their sperm than patients that failed (12.91 +/- 1.76 picomoles/10(6) cells) the test. CONCLUSIONS: PAF content in capacitated-induced sperm has a significant and positive relationship with fertilization potential. Fertilization potential may be predicted by measuring PAF levels in capacitation-induced human sperm. Determining PAF content in capacitated human sperm may be a beneficial diagnostic tool for the infertility specialist.