16. Relevance of Oocyte Morphology on ICSI Outcomes
KeywordsOocyte morphologyICSIEmbryo implantationClinical outcome
Interestingly, even the use of LH-containing drugs has been linked to a high recurrence of a particular oocyte dysmorphism, therefore leading to the debate on the role of urinary gonadotropins, native or purified, versus the recombinant FSH drugs [5, 6]. These oocyte characterizations evidenced an array of defects affecting its ability to undergo fertilization or to support the development of the resulting conceptus, albeit in an inconsistent manner.
Here we plan to revisit the occurrence and variety of specific ootid anomalies detected at the time of ICSI, in our own setting and population, to evaluate the eventual ability of these eggs to be fertilized, and to measure the competence of the resulting conceptus to implant. To control for a subtle effect inferred by ooplasmic dysmaturity, the data were analyzed in couples where at least 70% of the oocytes retrieved were at metaphase-II. Finally, in order to control for oocyte aneuploidy, the analysis was then carried out on couples with a female partner ≤35 years old.
16.1 Morphological Description
The terminology to describe oocyte morphology has generally found a consensus among the different laboratories with only small differences in nomenclature. For the purpose of analyzing the significance of each feature in relation to the oocyte function, we have categorized them into four groups: nuclear, cytoplasmic, zona pellucida, and shape/size. When assessing metaphase-II oocytes at the time of ICSI (carried out at a magnification of 400×), annotations were typically made for each individual oocyte detailing any dysmorphism observed by the ICSI operator. A normally developed metaphase-II oocyte should have a spherical zona pellucida enclosing a clear ooplasm and a distinct first polar body . In a cohort of 129,412 oocytes assessed at our center over a 10-year period, of all the morphological features, the top three most represented aberrations were a granular cytoplasm (6.07%), dark central granularity (5.76%), and a large perivitelline space (4.72%).
Cytoplasmic dysmorphic patterns
1. Fragmented PB
2. Large polar body
3. Two polar bodies
5. Refractile bodies
6. Smooth endoplasmic reticulum
7. Central granulation/dark center
9. Granular cytoplasm
10. Mottled cytoplasm
11. Expanse of the perivitelline space
12. Debris within perivitelline space
13. Dark zona pellucida
14. Thin zona pellucida
15. Abnormal zona pellucida
16. Bi-layered zona
17. Oocyte irregular in shape
18. Oval oocyte
19. Giant oocyte
The next most recurrent category at 8.1% concerns irregularities related to the zona pellucida such as a large perivitelline space, perivitelline debris, a dark zona pellucida, a thin zona pellucida, an abnormally shaped zona pellucida, and a bi-layered zona pellucida (Table 16.1, numbers 11–16).
16.2 Clinical Outcome
From October 2008 to May 2018, a total of 10,329 patients were treated in 12,580 ICSI cycles with at least five oocytes injected were included in the analysis with an average male partner age of 39.7 ± 7 years and a female partner 37.3 ± 5 years. Of these cycles, 58.6% had at least one oocyte with a morphological defect. Cycles that had inadequate ejaculated sperm parameters for ICSI (<1 million/mL) or that used surgically retrieved spermatozoa were excluded.
Superovulation was carried out by considering multiple factors such as patient weight, age, serum anti-mullerian hormone (AMH) level, antral follicular count, and any history of previous response to stimulation protocols. Patients were super-ovulated with gonadotropins daily (Gonal F, EMD Serono, Geneva, Switzerland; Menopur, Ferring Pharmaceuticals Inc., Parsippany, NJ, USA; and/or Follistim, Merck, Kenilworth, NJ, USA). Suppression of pituitary gland function was achieved by administering either a GnRH-antagonist (Ganirelix acetate, Merck, Kenilworth, NJ, USA; or Cetrotide, EMD-Serono Inc., Rockland, MA, USA) or GnRH-agonists (leuprolide acetate, Abbott Laboratories, Chicago, IL, USA). Ovulation was triggered with human chorionic gonadotropin (hCG, Ovidrel, EMD Serono) once the two lead follicles were at least 17 mm in diameter. Oocyte retrieval was performed 35–37 h post-trigger under conscious sedation .
We stratified these cases according to the percentage of oocytes displaying morphological anomalies in quartiles ranging from 0–24%, 25–49%, 50–74%, and 75–100% of oocytes having an annotation regarding a particular morphological feature. Clinical outcome including fertilization, clinical pregnancy, implantation, deliveries, and pregnancy loss were recorded and compared.