A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment

O’Neill, C.; Parrella, Alessandra; Keating, Derek; Cheung, Stephanie; Rosenwaks, Zev; Palermo, Gianpiero D.

doi:10.1007/s10815-018-1270-x

Cited by 31 publications

(31 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, we assessed aneuploidy on ejaculated and testicular spermatozoa, concurrently by FISH and NGS, in the same individuals. This was feasible because these men had a high DNA fragmentation in their ejaculate and preliminary studies have evidenced a lower SCF in spermatozoa retrieved directly from the seminiferous tubules [39]. In this analysis, we did observe a similar aneuploidy rate in testicular spermatozoa; indeed it was lower ( P <0.0001).…”

Section: Discussionsupporting

confidence: 62%

Revisiting aneuploidy profile of surgically retrieved spermatozoa by whole exome sequencing molecular karyotype

2019

View full text Add to dashboard Cite

Previous studies, including our own, have reported that spermatozoa isolated from the testis have remarkably higher occurrence of aneuploidy once isolated from azoospermic men. This notion, however, did not translate into a lower pregnancy rate nor a greater proportion of miscarriages. Indeed, ICSI offspring generated from surgically retrieved gametes did not suffer from increased karyotypic aneuploidy than children generated from ejaculated specimens. In recent years, aneuploidy assessments on a larger number of cells and utilizing more chromosome probes have reported a progressive decrease in chromosomal aberrations in spermatozoa directly retrieved from the seminiferous tubules. In light of the availability of more accurate molecular genetic techniques, we have decided to challenge the notion that sampling epididymal and testicular tissues yields spermatozoa with higher incidence of aneuploidy than those retrieved in the ejaculate. In a retrospective manner, we have carried out an analysis by FISH with 9 chromosome probes on at least 1000 cells from the ejaculates of 87 consenting men and the specimens of 6 azoospermic men, while spermatozoa of fertile donors were used as control. Aneuploidy by FISH yielded 0.9% for the donor control but rose in the study group to 3.6% in the ejaculated, 1.2% for the epididymal, and 1.1% for testicular spermatozoa. There were no differences in autosomal or gonosomal disomies, nor nullisomies. In this group, once the specimens of these men were used for ICSI, ejaculated spermatozoa yielded a 22% clinical pregnancy rate that resulted in 62.5% pregnancy loss. The surgically retrieved specimens yielded a 50% clinical pregnancy rate that progressed to term. To confirm our findings, in a prospective analysis, DNA sequencing was carried out on the ejaculates and surgical samples of 22 men with various spermatogenic characteristics. In this comparison, the findings were similar with actually a higher incidence of aneuploidy in the ejaculated spermatozoa (n = 16) compared to those surgically retrieved (n = 6) (P<0.0001). For this group, the clinical pregnancy rate for the ejaculated specimens was 47.2% with 29.4% pregnancy loss, while the surgically retrieved yielded a 50% clinical pregnancy rate, all progressing to term. A subsequent prospective combined assessment on ejaculated and surgically retrieved spermatozoa by FISH and NGS was performed on non-azoospermic men with high DNA fragmentation in their ejaculate. The assessment by FISH evidenced 2.8% chromosomal defects in the ejaculated and 1.2% in testicular biopsies while by NGS became 8.4% and 1.3% (P = 0.02), respectively. Interestingly, we evidenced a pregnancy rate of 0% with ejaculated while 100% with the testicular spermatozoa in this latter group. This indicates that improved techniques for assessing sperm aneuploidy on a wider number of cells disproves earlier reports and corroborates the safe utilization of testicular spermatozoa with a positive impact on chances of pregnancy.

show abstract

Section: Discussionsupporting

confidence: 62%

Revisiting aneuploidy profile of surgically retrieved spermatozoa by whole exome sequencing molecular karyotype

2019

View full text Add to dashboard Cite

show abstract

“…SDF testing can serve as an ancillary test to conventional semen analysis in specific clinical scenarios. Evidence indicates that higher levels of SDF are observed in patients who are unable to conceive naturally [149,[273][274][275], who present with UMI/idiopathic infertility [185,188,[276][277][278][279][280][281][282], have RPL [116,138,[180][181][182][183][283][284][285][286][287][288][289][290][291][292][293][294][295], are diagnosed with varicocele [169][170][171][172][173][174][296][297][298][299][300][301][302][303][304]…”

Section: Strengthsmentioning

confidence: 99%

“…SDF testing can serve as an ancillary test to conventional semen analysis in specific clinical scenarios. Evidence indicates that higher levels of SDF are observed in patients who are unable to conceive naturally [ 149 273 274 275 ], who present with UMI/idiopathic infertility [ 185 188 276 277 278 279 280 281 282 ], have RPL [ 116 138 180 181 182 183 283 284 285 286 287 288 289 290 291 292 293 294 295 ], are diagnosed with varicocele [ 169 170 171 172 173 174 296 297 298 299 300 301 302 303 304 305 ], have a negative ART outcome [ 13 41 88 117 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 …”

Section: Strengths-weaknesses-opportunities-threats (Swot) Analysis Omentioning

confidence: 99%

Sperm DNA Fragmentation: A New Guideline for Clinicians

Agarwal

Majzoub

Baskaran

et al. 2020

World J Mens Health

169

144

View full text Add to dashboard Cite

Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations. This article provides an overview of SDF types, origin and comparative analysis of various SDF assays while primarily focusing on the clinical indications of SDF testing. Importantly, we report four clinical cases where SDF testing had played a significant role in improving fertility outcome. In light of these clinical case reports and recent scientific evidence, this review provides expert recommendations on SDF testing and examines the advantages and drawbacks of the clinical utility of SDF testing using Strength-Weaknesses-Opportunities-Threats (SWOT) analysis.

show abstract

“…After observing couples with unexplained infertility after a failed IUI, we designed a reproductive treatment algorithm based on a sperm DNA fragmentation assay [13]. According to this algorithm, if the male gamete chromatin integrity is confirmed, the couple can proceed to standard in vitro insemination.…”

Section: Introductionmentioning

confidence: 99%

“…ICSI would also be offered to men who, in spite of having spermatozoa with healthy chromatin, failed to achieve a pregnancy with standard in vitro insemination. Finally, for cases in which a pregnancy has not been achieved even with ICSI, men are counseled by a reproductive urologist and offered a cycle of ICSI using spermatozoa retrieved directly from the testicle [13, 14], where SCF appears to be consistently lower [15, 16].…”

Section: Introductionmentioning

confidence: 99%

A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure

Parrella

Keating

Cheung

et al. 2019

J Assist Reprod Genet

View full text Add to dashboard Cite

ObjectiveTo test a novel method to select spermatozoa with high chromatin integrity.DesignSpecimens with high sperm chromatin fragmentation (SCF) were selected by density gradient selection (DGS) and microfluidic sperm sorting (MSS).SettingAcademic medical center.Patient(s)Ejaculates from consenting men were processed by DGS/MSS. Couples underwent ICSI cycles with spermatozoa processed by DGS/MSS. Clinical outcomes were evaluated after embryo transfer.Intervention(s)SCF was measured by TUNEL. ICSI with spermatozoa selected by DGS and MSS was performed.Main outcome measure(s)Fertilization, embryo implantation, and pregnancy outcomes were compared between DGS and MSS.Result(s)A total of 23 men had an average SCF of 20.7 ± 10%. After DGS and MSS, the SCF was 12.5 ± 5% and 1.8 ± 1%, respectively. In couples who underwent ICSI, the average SCF was 28.8 ± 9%, which fell to 21.0 ± 9% after DGS and 1.3 ± 0.7% after MSS. Four couples underwent 11 ICSI cycles with DGS and achieved one (25%) pregnancy that resulted in pregnancy loss. In four subsequent ICSI cycles with MSS, an ongoing clinical pregnancy rate of 50% was achieved. Five additional couples underwent 12 cycles of ICSI with DGS. After preimplantation genetic testing for aneuploidy, 30.3% of the embryos were euploid. One pregnancy was achieved, resulting in pregnancy loss. With MSS, 31.5% of the embryos were euploid and 4 couples obtained a pregnancy. Finally, sixteen couples underwent 20 ICSI cycles solely with MSS at our center. Of these couples, 8 had failed 13 ICSI cycles with DGS elsewhere. These couples achieved an overall implantation of 34.5% (10/29) and a pregnancy rate of 58.8% (10/17).Conclusion(s)Microfluidic selection yielded spermatozoa with optimal genomic integrity and improved chances of obtaining a euploid conceptus.

show abstract

A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment

Cited by 31 publications

References 27 publications

Revisiting aneuploidy profile of surgically retrieved spermatozoa by whole exome sequencing molecular karyotype

Revisiting aneuploidy profile of surgically retrieved spermatozoa by whole exome sequencing molecular karyotype

Sperm DNA Fragmentation: A New Guideline for Clinicians

A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure

Contact Info

Product

Resources

About