Does paternal age affect the live birth rate in donor oocyte cycles? A systematic review and meta-analysis.

PURPOSE: While delayed parenthood is increasing worldwide, the effect of paternal age on in vitro fertilization (IVF) outcomes remains unclear. The egg donation model appears to be relevant to studying the independent impact of paternal age on clinical outcome, but the available studies are heterogeneous and contradictory. This systematic review and meta-analysis aimed to assess the relationship between paternal age and live birth rate (LBR) in egg donation cycles. METHODS: A systematic search of the literature was conducted in PubMed, Embase, and the Cochrane Library from inception to June 30, 2021. All studies on egg donation cycles where LBR is reported according to male age were included. Study selection, bias assessment, and data extraction were performed by two independent reviewers according to the Cochrane methods. RESULTS: Eleven studies involving 10,527 egg donation cycles were finally included. The meta-analysis showed a slight but significant and linear decrease in LBR with increasing paternal age (estimate - 0.0055; 95% CI (- 0.0093; - 0.0016), p = 0.006), with low heterogeneity (I2 = 25%). No specific threshold was identified. A similar trend toward decreased clinical pregnancy rate with advancing paternal age was found but did not reach statistical significance (p = 0.07). CONCLUSION: This meta-analysis demonstrates that increasing paternal age is associated with a slight but significant and linear decrease in the live birth rate in egg donation cycles, with no apparent threshold effect. Although this requires further confirmation, this information is important for counseling men who are considering delayed childbearing.

Cyclic FEE Peptide Improves Human Sperm Movement Parameters without Modification of Their Energy Metabolism.

Cyclic fertilin peptide (cFEE: phenylalanine, glutamic acid; glutamic acid) improves gamete interaction in humans. We investigate whether it could be via improvement of sperm movement parameters and their mitochondrial ATP production. Sperm movement parameters were studied using computer-assisted sperm analysis (CASA) in sperm samples from 38 patients with normal sperm in medium supplemented with cyclic fertilin against a control group. Sperm mitochondrial functions were studied using donor's sperm, incubated or not with cFEE. It was evaluated by the measurement of their ATP production using bioluminescence, their respiration by high resolution oxygraphy, and of mitochondrial membrane potential (MMP) using potentiometric dyes and flow cytometry. cFEE significantly improved sperm movement parameters and percentage of hyperactivated sperm. Impact of inhibitors showed OXPHOS as the predominant energy source for sperm movement. However, cFEE had no significant impact on any of the analyzed mitochondrial bioenergetic parameters, suggesting that it could act via a more efficient use of its energy resources.

The high frequency of sperm aneuploidy in klinefelter patients and in nonobstructive azoospermia is due to meiotic errors in euploid spermatocytes.

For nonobstructive azoospermic (NOA) patients with a normal karyotype or for Klinefelter syndrome (47,XXY) patients, intracytoplasmic sperm injection is associated with an increased aneuploidy risk in offspring. We examined testicular cells from patients with different azoospermia etiologies to determine the origin of the aneuploid spermatozoa. The incidence of chromosome abnormalities was investigated in all types of azoospermia. Four study subgroups were constituted: Klinefelter patients (group 1), NOA patients with spermatogenesis failure but a normal karyotype (group 2), obstructive azoospermic patients with normal spermatogenesis (group 3), and control patients with normal sperm (group 4). The pachytene stage (in the three azoospermic groups) and postmeiotic cells (in all groups) were analyzed with fluorescence in situ hybridization. No aneuploid pachytene spermatocytes were observed. Postmeiotic aneuploidy rates were higher in the two groups with spermatogenesis failure (5.3% and 4.0% for groups 1 and 2, respectively) than in patients with normal spermatogenesis (0.6% for group 3 and group 4). Whatever the etiology of the azoospermia, the spermatozoa originated from euploid pachytene spermatocytes. These results strengthen the hypothesis whereby sperm aneuploidy in both Klinefelter patients and NOA patients with a normal karyotype results from meiotic abnormalities and not from aneuploid spermatocytes. The fact that sperm aneuploidy was more frequent when spermatogenesis was altered suggests a deleterious testicular environment. The study results also provide arguments for offering preimplantation genetic diagnosis or prenatal diagnosis when a pregnancy occurs for fathers with NOA (whatever the karyotype).

Seminal leukocytes are Good Samaritans for spermatozoa.

OBJECTIVE: To assess the effect of leukocytospermia on assisted reproductive technology outcomes. DESIGN: Retrospective analysis. SETTING: University laboratory. PATIENT(S): Couples attending the infertiliy clinic and involved in ART program for IVF or ICSI. INTERVENTION(S): During a 7-year follow-up in an assisted reproductive technology program, leukocytospermia was routinely determined using the peroxidase technique. Donor sperm were excluded from the study. MAIN OUTCOME MEASURE(S): Egg retrievals (N = 3,508) were distributed in 3 groups according to the leukocyte levels in semen from which fertilizing sperm were extracted: group 1, absence of leukocytes (n = 3,026); group 2, moderate leukocytospermia (<10(6)/mL) (n = 344); or group 3, high leukocytospermia (≥10(6)/mL) (n = 138). They resulted in 1,463 IVF and 2,045 intracytoplasmic sperm injection procedures that gave 802 clinical pregnancies. RESULT(S): Surprisingly, the fertilization rate, cleavage rate, clinical pregnancy rate, gestational age, and mean infant weight were significantly improved when seminal leukocytes were present, regardless of the technique used. The only negative side effects associated with a high level of seminal leukocytes (group 3) were an elevated rate of early pregnancy loss (from 26.6% to 40.5%) and a 3-fold increase in the percentage of ectopic pregnancies. CONCLUSION(S): At moderate levels (<10(6)/mL), leukocytospermia appears to be physiologic. It is associated with improved sperm fertilization ability and pregnancy outcome. At higher concentrations, leukocytospermia alters neither sperm fertilization ability nor the probability of clinical pregnancy when compared with nonleukocytic patients with infertility. However, the pregnancy outcome is reduced.

Seminal leukocytes and clinical outcomes with donor sperm insemination.

OBJECTIVE: To report the level of leukocytospermia in fertile donors' semen. Surprisingly, seminal leukocytes protect fertilization properties of sperm and are associated with normal or improved assisted reproductive technology outcomes in infertility patients. This raises the question of whether leukocytospermia exists in fertile men as well. We report a study of sperm donors who, by law in France, have to be of proven fertility. DESIGN: Retrospective analysis. SETTING: University laboratory. PATIENT(S): One hundred fifty-five donors were selected for cryobanking. Results of their sperm analyses were compared with those from 10,242 infertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The men's first ejaculate was studied by cytologic analysis to determine the round cell and polymorphonuclear cell (PMN) contents. A total of 3,875 donor sperm inseminations (DSIs) were performed, and their outcomes were analyzed over an 8-year period. RESULT(S): PMN is more elevated in semen from infertility patients than in semen from fertile donors, but some donors (6.5%) had high leukocytospermia (≥10(6)/mL). The post-DSI pregnancy rate was increased when round cells were present (P<.02) but not with higher PMN concentrations. Furthermore, high leukocytospermia was associated with an increased post-DSI miscarriage rate. CONCLUSION(S): In fertile donors, as in infertility patients, high leukocytospermia (>10(6)/mL) is associated with a normal pregnancy rate but an increased percentage of early pregnancy loss.

A prospective randomized study to compare four different mineral oils used to culture human embryos in IVF/ICSI treatments.

OBJECTIVE(S): We aimed to evaluate and compare the embryo quality at early cleavage stages using different oils overlaying media to culture human embryos during IVF/ICSI treatments. STUDY DESIGN: A total of 500 IVF/ICSI treatments from 500 women were analyzed in a prospective randomized study. Oocytes/embryos were treated into microdroplets of appropriate media overlaid with (i) Mineral Oil (CryoBioSystem, L'Aigle, France) (group 1, n=129), (ii) Liquid Paraffin (Medicult, Lyon, France) (group 2, n=126), (iii) Nidoil (Nidacon International, Guthenburg, Sweden) (group 3, n=126) and (iv) Ovoil (Vitrolife, Kungsbacka, Sweden) (group 4, n=119). Comparisons between groups were done using two by two post hoc tests, with 5% significance. The primary endpoint was the embryo quality, defined as good or top quality when embryos were with (i) less than 20% of fragmentation and (ii) 3-5/4 cells at day 2 or 6-10/8 cells at day 3, respectively. RESULTS: At day 2, the embryo quality was similar in all groups. However, the mean number of top quality embryos at day 3 was statistically higher into the group 4 (1.4+/-1.8) compared to the group 1 (0.9+/-1.0; p=0.03) and 2 (0.8+/-1.3; p=0.05). Furthermore, a significant increase of the mean number of good quality embryos was observed at day 3 into the group 4 (2.6+/-2.6) compared to the group 1 (1.6+/-1.6; p=0.02). CONCLUSION(S): The embryo quality could be modified according to commercial oils used to overlay culture media.