ORIGINAL ARTICLE |
https://doi.org/10.5005/jogyp-11012-0014
|
Impact of Oocytes with Mild and Heavy Debris in Perivitelline Space on Blastocyst Quality
1Department of Obstetrics and Gynaecology, Saveetha Medical College, Chennai, Tamil Nadu, India
2,3Department of Clinical Embryology, ARC International Fertility and Research Centre, Chennai, Tamil Nadu, India
4,5Department of Reproductive Medicine, Saveetha Medical College, Chennai, Tamil Nadu, India
Corresponding Author: Dinesh Ram V, Department of Obstetrics and Gynaecology, Saveetha Medical College, Chennai, Tamil Nadu, India, Phone: +91 6381446552, e-mail: vldineshram2812@gmail.com
How to cite this article: Ram VD, Chandan N, Mahalakshmi, et al. Impact of Oocytes with Mild and Heavy Debris in Perivitelline Space on Blastocyst Quality. J Obstet Gynaecol Pract POGS 2023;1(2):42–48.
Source of support: Nil
Conflict of interest: None
Received on: 29 July 2023; Accepted on: 30 August 2023; Published on: 22 November 2023
ABSTRACT
Aim: The aim of this study is to compare the blastocyst quality of oocytes with mild and heavy debris in perivitelline space (DPVS).
Objective: To investigate the rate of blastocyst development of oocytes with mild DPVS and to investigate the rate of blastocyst development of oocytes with heavy DPVS, then to compare the rate of blastocyst development of oocytes with mild and heavy DPVS and to identify ideal blastocyst for transfer.
Study population: Patients who have undergone controlled ovarian stimulation for the intracytoplasmic sperm injection (ICSI) cycle from March 2023 to May 2023 ARC International Fertility and Research Centre.
Study groups: Two groups were considered—oocytes with mild debris or granularity in perivitelline space (PVS) and oocytes with heavy debris or granularity in PVS.
Results: This study from March 2023 to May 2023 was done at ARC International Fertility and Research Centre. Patients undergoing the Antagonist protocol for the ICSI cycle were considered. Around 371 M2 oocytes were analyzed, in that 203 had mild debris or granularity in PVS and 168 had heavy debris or granularity in PVS.
In oocytes with mild debris or granularity in PVS, their fertilization rate, cleavage rate, and frozen blastocyst rate are 88, 81, and 47%, respectively. In oocytes with heavy debris or granularity in PVS their fertilization rate, cleavage rate, and frozen blastocyst rate are 76, 59, and 15%, respectively.
Oocytes with heavy debris or granularity in PVS have compromised blastocyst quality compared with mild debris or granularity in PVS.
Conclusion: In this study, we conclude that debris or granularity in PVS can be considered an indicator of oocyte competence. This can help in identifying a cohort of oocytes with a lower chance of forming viable embryos. This helps in reducing the culture of supernumerary embryos. We suggest that when the patients enroll for donor oocytes, oocytes without heavy debris or granularity in PVS should be used because heavy granularity in PVS has compromised blastocyst conversion. Further studies are needed with a large sample size to get a conclusion.
Keywords: Human menopausal gonadotropin, Perivitelline space, Zona pellucida.
INTRODUCTION
Fertility in humans refers to the ability to conceive and reproduce. It involves several factors, including the quality and quantity of gametes (sperm and eggs), the reproductive health of both partners and the timing of intercourse.1–4
Infertility is a common medical problem, where the couple cannot conceive within one year of active sexual intercourse. The fertility investigations for females include evaluation of ovulation and tubal patency investigations for males include semen parameters. Infertility can be due to male factor or female factor or combined factors (WHO 1999).5–8 In developed countries, around 2–4% of births occur due to assisted reproductive technology (ART).
Intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) come under ART which has therapeutic means for infertility.9–12
The male reproductive system functions to produce (spermatogenesis) and deposit sperm.13 The sperm carries 23 pairs of chromosomes and a centrosome. The female reproductive system functions to produce oocytes (oogenesis) and to protect and nourish the fetus until birth. The oocyte is one of the largest cells in the human body.14,15
Human reproduction involves the fertilization of sperm and egg which occurs in the ampulla of the fallopian tube.16–19 This results in the production of a zygote or a fertilized oocyte. The stages of fertilization can be divided into sperm oocyte fusion, sperm capacitation, acrosome reaction, sperm penetration into zona pellucida (ZP), and sperm penetration into PVS.20
During ICSI the sperm is directly injected into the ooplasm, which leads to bypassing the zona reaction and sperm oocyte penetration.21–25 Furthermore, ICSI increases the probability of fertilization rate which leads to an increase in success rate.26
Sperm have three main structural regions: the head, midpiece, and tail (flagellum). While the midpiece and tail provide the motility necessary for the spermatozoon to reach the site of fertilization, the sperm head contributes its haploid set of chromosomes to the oocyte at fertilization. The sperm head contains the nuclear DNA which is heavily condensed by the associations between DNA and protamines.27–32
Controlled ovarian stimulation protocol ensures retrieval of mature oocytes for IVF or ICSI. Protocols such as agonist (long protocol) and antagonist (short protocol) are commonly followed. Agonist protocol involves suppression of the hypothalamic–pituitary–ovarian (HPO) axis. Antagonist protocol involves blockage of gonadotropin-releasing hormone (GnRH) receptors which inhibits gonadotropin secretion. The trigger is given when the follicle reaches 17–18 mm. The trigger given can be either human choriogonadotropin (HCG) or an agonist trigger. Human choriogonadotropin has an alpha subunit and a beta subunit.33–35 The alpha subunit is similar to that of LH and hence binds to LH receptors. Agonist trigger helps in reducing the risk of ovarian hyperstimulation syndrome (OHSS) but may cause luteal phase defect. The trigger is given to loosen the cumulus cells from the follicular wall; this facilitates the release of oocytes after 34–36 hours.36–38
Oocyte is a cell in an ovary that may undergo meiotic division to form an ovum. Its size ranges from 100 to 120 µm. Oocyte with normal morphology has expanded cumulus with radiant corona, bright cytoplasm, intact polar body (PB), ZP with thickness 18–22 µm, perivitelline space (PVS) with no granularity.39–45
Oocyte dysmorphism can be divided into intracytoplasmic anomalies, extracytoplasmic anomalies, and oocytes with abnormal size and shape.
Intracytoplasmic anomalies: Granular and dark oocytes, vacuoles, refractile bodies, smooth endoplasmic reticulum (SER).
Extracytoplasmic anomalies: Thin, thick, or dark ZP, enlarged PVS and abnormal PB morphology.
Abnormal size and shape: Giant oocyte, oval oocyte, and abnormal-shaped cytoplasm
Oocyte morphology can be assessed to find viable embryos. Embryo grading results may vary between clinics, and grading of day 2 or day 3 embryos or blastocysts remains challenging. Assessing oocyte morphology reduces the culture time (helps in the selection and culturing of viable embryos) and zona hardening can be avoided. This helps in identifying the ideal blastocyst for transfer. Identifying ideal blastocyst leads to better pregnancy rates.
What is Perivitelline Space?
Perivitelline space is the space between ZP and the cell membrane of an oocyte in which the extruded first PB is present. Cortical granules released from the ovum get deposited in PVS to block polyspermy (in normal fertilization). If the PVS is normal, the ooplasm is slightly away from the ZP in the surrounding area of the PB.
Abnormalities in PVS can be large PVS (in particular side or around the oocyte), granular or debris in perivitelline space (DPVS), or absence of PVS. Factors such as female age did not affect PVS, but the ratio of estradiol to testosterone (and to progesterone) did. Granularity in PVS is related to maturation events. Some of the studies proved the correlation between doses of human menopausal gonadotropin (HMG) and granularity in PVS. In some cases, the remnants of coronal cells deposit as granules in PVS, which usually withdraws when meiosis resumes. Studies regarding the correlation between granularity in PVS and embryo quality remain controversial. Various authors studied the correlation between granularity in PVS and fertilization rate, blastocyst quality, and pregnancy rate. The aim of this study is to assess the blastocyst quality of oocytes with mild and heavy DPVS.
AIM
The aim of this study is to compare the blastocyst quality of oocytes with mild and heavy DPVS.
OBJECTIVE
To investigate the rate of blastocyst development of oocytes with mild DPVS.
To investigate the rate of blastocyst development of oocytes with heavy DPVS.
To compare the rate of blastocyst development of oocytes with mild and heavy DPVS and to identify the ideal blastocyst for transfer.
To enhance the pregnancy rate.
MATERIALS AND METHODOLOGY
Study Design
Prospective analytical study.
Study Setting
ARC International Fertility and Research Centre.
Inclusion Criteria
Age, 21–45 years; BMI, 18–38 kg/m2; marital life, above 5 years; previous IUI failure; sterilization/unexplained infertility; tubal anomaly and polycystic ovarian disease (PCOD); antagonist protocol; extracytoplasmic abnormalities (DPVS or granularity in PVS); oocyte with normal morphology; and sperm quality mild/moderate (oligo-, astheno-, and teratozoospermia); donor sperm.
Exclusion Criteria
Vitrified/thawed oocytes; surgical sperm retrieval; agonist protocol; and other oocyte abnormalities.
Study Population
Patients who have undergone Controlled ovarian stimulation for the ICSI cycle from March 2023 to May 2023 International Fertility and Research Centre.
This study has been reviewed and approved by the institutional ethical committee of Saveetha University (SMC/IEC/2021/12/007). After ensuring that the patients satisfied the inclusion and exclusion criteria, all the patients were provided with written informed consent to use their gametes for this study.
Study Groups
Two groups were considered—oocytes with mild debris or granularity in PVS and oocytes with heavy debris or granularity in PVS.
Controlled Ovarian Hyperstimulation
Stimulation was started from day 2 of the menstrual cycle. The patients will undergo the antagonist protocol, in which they will receive stimulation using different medications. These medications include urinary follicle-stimulating hormone (FSH), folliculin–urofollitropin (Bharath Serums and Vaccines Limited, Ambernath, Maharashtra, India), recombinant FSH, follisurge (Intas Pharmaceuticals Limited, Ahmedabad, Gujarat, India), or urinary HMG, IVF M (Cipla, Mumbai, Maharashtra, India). At around day 5 of stimulation, when the follicle reaches 12–14 mm, an antagonist such as Ciscure (Cetrorelix acetate, Emcure Pharmaceuticals Limited, Hinjewadi, Pune, Maharashtra, India) or Ovurelix (Cetrorelix acetate, Sun Pharmaceutical industries limited, Mumbai, Maharashtra, India) will be administered. Once the follicles reach 18–20 mm, a trigger will be given. The type of trigger administered will be decided based on the follicle count and E2 level. Patients with a high E2 level (>6000 pg/mL) and follicle count will receive an agonist trigger, Decapeptyl 0.2 mg (Triptorelin Acetate, Ferring Pharmaceuticals Limited, Thane). Patients with E2 < 5000 pg/mL and a low follicle count will receive Ovitrelle 250 µg (Recombinant HCG, Merck, Bhiwandi, Maharashtra, India). Patients with a low follicle count and high E2 level will receive a dual trigger (HCG 5000 IU and Leuprolide 0.2 mg).46
Sample Preparation
Semen Analysis was done based on the WHO Manual for Human Semen Analysis, 6th edition. Samples will be obtained by ejaculation. Cell counter and light microscope will be used to determine sperm count and motility (Fig. 1). Morphology will be evaluated by eosin staining. All the samples will be prepared either by density gradient or simple wash. The prepared sample will be incubated at 37°C in 6% CO2 until used it.
Oocyte Retrieval and Denudation
Follicular fluid will be screened and cumulus oocyte complex (COC) will be collected using sterile glass pipettes (Fig. 2) and incubated in culture media for about 2 hours before denudation. The cumulus complex was denuded with HYDASE (Vitromed, Langenfeld, Germany) using mechanical stripping using denuding pipettes. After denudation, M II oocytes will be washed with HEPES (Vitromed, Langenfeld, Germany) After washing, Oocyte morphology was assessed using a microscope. Oocytes with other morphological abnormalities were excluded.
Intracytoplasmic Sperm Injection
Intracytoplasmic sperm injection will be carried out on the heated stage (37°C) of an inverted microscope (Olympus, Japan) at 400× magnification using a Narishige micromanipulator (Sony Corporation, Japan). Morphologically normal sperms will be selected for ICSI. Also, ICSI was done 2 hours postdenudation. Polyvinylpyrrolidone (PVP; Vitromed, Langenfeld, Germany) was used to decrease sperm motility. Holding and injection pipettes (Vitromed, Langenfeld, Germany) were used. Holding injection was used to hold the oocyte, injection needle was used to inject the sperm. After insemination, oocytes with mild and heavy debris were cultured in separate wells in a culture dish containing step media (one step; Vitromed, Langenfeld, Germany) droplet overlayer by oil (paraffin oil; Vitromed, Langenfeld, Germany).
Assessment of Fertilization: Embryo Cleavage and Blastocyst Formation
About 16–18 hours post-ICSI (day 1), fertilization check was done. Presence of two pronuclei (2PN) or two polar bodies (2PB) was considered normal fertilization. Presence of one polar body (1PN) or three pronuclei (3PN) was considered abnormal fertilization. Unfertilized oocytes and degenerate oocytes (damaged oocyte inside ZP) was also observed during fertilization check. Only the zygotes with 2PN or 2PB forms viable embryos.
Based on the number of cells, rate of fragmentation, symmetric blastomeres and absence of multi nucleation day 3 embryos will be assessed. About 68 ± 1-hours post-ICSI (day 3) embryo cleavage was assessed.
About 116 ± 2 hours post-ICSI (day 5) blastocysts develop. Blastocyst can be observed on day 5 and day 6. However, day-5 blastocysts are more viable than day 6 blastocysts. According to the Gardner grading system blastocyst was graded.
About 371 M2 oocytes were analyzed, and in that, 203 has mild debris or granularity in PVS (Fig. 3) and 168 has heavy debris or granularity in PVS (Fig. 4). Fertilization, cleavage, and blastocyst from both the groups were observed and noted separately.
Statistical Analysis
The p-value defines the probability of getting a result that is either the same or more extreme than the other actual observations. The p-value represents the probability of occurrence of the given event. If the p-value is 0.05 or lower, the result is declared as significant, but if it is higher than 0.05, the result is non-significant.47,48
Two-sample t-test with unequal variance is a two-sample location test which is used to test the (null) hypothesis that two populations have equal means. This test is often referred to as “unpaired” or “independent samples” t-tests and is more reliable when the two samples have unequal variances and possibly unequal sample sizes.49–54
Frequency refers to the number of times an event or a value occurs. A frequency table is a table that lists items and shows the number of times the items occur.55–58
The statistical analysis was done to compare the blastocyst rate of oocytes with mild debris or granularity in PVS and heavy debris or granularity in PVS (Figs 5 to 8). The statistical analysis was done using two-sample t-test with unequal variances; p < 0.05 were considered significant.59
The fertilization rate, cleavage rate, and day-3 good embryos rate were presented in a frequency table. Microsoft Excel was used for statistical analysis.60
Comparison of Blastocyst Rate of Oocytes with Mild Debris or Granularity in PVS and Heavy Debris or Granularity in PVS and Heavy DPVS
Hypothesis
Null hypothesis: There is no significant difference between the effect of mild and heavy debris.
Alternative hypothesis: Heavy debris has a negative impact on blastocyst rate.
Two-sample t-test with unequal variances (Table 1).
Variable 1 | Variable 2 | |
---|---|---|
Mean | 4 | 0.961538 |
Variance | 6.173913 | 2.518462 |
Observations | 24 | 26 |
Hypothesized mean difference | 0 | |
df | 39 | |
t-statistics | 5.1060431 | |
p (T ≤ t) one tail | 0.00000448 | |
t-critical one tail | 1.6848751 | |
p (T ≤ t) two tails | 0.00000896 | |
t-critical two tails | 2.0226909 |
Interpretation
The null hypothesis is rejected because the p-value (0.00000896) is smaller than the level of significance (0.05). Hence, the oocytes with heavy debris or granularity in PVS affected the blastocyst rate (Tables 2 to 7).
Row labels | Sum of fertilization | Sum of cleavage | Sum of blastocyst |
---|---|---|---|
Heavy | 128 | 99 | 25 |
Mild | 179 | 164 | 96 |
Grand total | 307 | 263 | 121 |
Fertilized rate | ||
---|---|---|
Mild | Heavy | |
Average | 7.458333 | 4.923077 |
Median | 7 | 3.5 |
Mode | 6 | 1 |
Variance | 14.51993 | 23.27385 |
Standard | 3.810502 | 4.824297 |
deviation |
Cleavage rate | ||
---|---|---|
Mild | Heavy | |
Average | 6.833333 | 3.807692308 |
Median | 7 | 2 |
Mode | 2 | 1 |
Variance | 12.31884 | 18.88153846 |
Standard | 3.509821 | 4.345289226 |
deviation |
Blastocysts rate | ||
---|---|---|
Mild | Heavy | |
Average | 6.833333333 | 3.807692 |
Median | 7 | 2 |
Mode | 2 | 1 |
Variance | 12.31884058 | 18.88154 |
Standard deviation | 3.509820591 | 4.345289 |
Observation | |
---|---|
Mild debris or granularity in PVS group | |
Total number of M2 oocytes | 203 |
Number of fertilized oocytes | 179 (88%) |
Number of cleaved oocytes | 164 (81%) |
Number of blastocysts | 115 (57%) |
Number of frozen blastocysts | 96 (47%) |
Heavy DPVS or granularity in PVS group | |
---|---|
Total number of M2 oocytes | 168 |
Number of fertilized oocytes | 128 (76%) |
Number of cleaved oocytes | 99 (59%) |
Number of blastocysts | 39 (23%) |
Number of frozen blastocysts | 25 (15%) |
RESULTS
This study from March 2023 to May 2023 was done at ARC International Fertility and Research Centre. Patients undergoing Antagonist protocol for ICSI Cycle were considered. Around 371 M2 oocytes were analyzed, in that 203 has mild debris or granularity in PVS and 168 has heavy debris or granularity in PVS.
In oocytes with mild debris or granularity in PVS, their Fertilization rate, cleavage rate, and frozen blastocyst rate are 88, 81, and 47%, respectively. In oocytes with heavy debris or granularity in PVS, their fertilization rate, cleavage rate, and frozen blastocyst rate are 76, 59, and 15%, respectively.
Oocytes with Heavy debris or granularity in PVS has compromised blastocyst quality compared with mild debris or granularity in PVS.
DISCUSSION
Assessing the quality of oocytes helps in minimizing the culture time which benefits both patients and clinics.61–63 Also preselecting the embryos based on oocyte morphology can be done on the day of OCR by non-invasive selection. Some of the countries such as Italy have regulations for ART, where only three oocytes can be inseminated per cycle. Insemination of all the oocytes and embryo cryopreservation is outlawed. Hence selection of good-quality oocytes for ICSI plays a significant role in the above-mentioned cases.64,65
From the results of certain studies, the effect of extra-cytoplasmic abnormalities remains controversial. Most of the studies had concluded that DPVS has compromised blastocyst quality but in some of the cohort studies blastocyst quality was moderate. Till now there is no study comparing mild and heavy debris.66,46
CONCLUSION
In this study, we conclude that debris or granularity in PVS can be considered as indicator of oocyte competence. This can help in identifying a cohort of oocytes with a lower chance of forming viable embryos. This helps in reducing the culture of supernumerary embryos.
We suggest that when the patients enroll for donor oocytes, oocytes without heavy debris or granularity in PVS should be used because heavy granularity in PVS has compromised blastocyst conversion. In this study, we analyzed around 371 oocytes; further studies need to be done with a large sample size to get a conclusion.67,68
ORCID
Dinesh Ram V https://orcid.org/0009-0005-5196-9529
REFERENCES
1. Adhikari D, Liu K. The regulation of maturation promoting factor during prophase I arrest and meiotic entry in mammalian oocytes. Mol Cell Endocrinol 2014;385(1–2):12–20. DOI: 10.1016/j.mce.2014.02.011.
2. Alpha Scientists in Reproductive Medicine, ESHRE Special Interest Group of Embryology. The Vienna consensus: Report of an expert meeting on the development of ART laboratory performance indicators. Reprod Biomed Online 2017;35(5):494–510. DOI: 10.1016/j.rbmo.2017.06.015.
3. Balakier H, Bouman D, Sojecki A, et al. Morphological and cytogenetic analysis of human giant oocytes and giant embryos. Hum Reprod 2002;17(9):2394–2401. DOI: 10.1093/humrep/17.9.2394.
4. Bermejo A, Iglesias C, Ruiz–Alonso M, et al. The impact of using the combined oral contraceptive pill for cycle scheduling on gene expression related to endometrial receptivity. Hum Reprod 2014;29(6):1271–1278. DOI: 10.1093/humrep/deu065.
5. Carson CC III, Lipshultz LI, Howards SS. Male reproductive function and semen. In: Wein AJ, Kavoussi LR, Novick AJ, et al., editors. Campbell–Walsh Urology, 11th edition. Philadelphia: Elsevier; 2016.
6. Cheng CY, Mruk DD. The blood–testis barrier and its implications for male contraception. Pharmacol Rev 2012;64(1):16–64. DOI: 10.1124/pr.110.002790.
7. Conti M, Andersen CB, Richard F, et al. Role of cyclic nucleotide signaling in oocyte maturation. Mol Cell Endocrinol 2002;187(1–2):153–159. DOI: 10.1016/s0303-7207(01)00686-4.
8. Cornwall GA, von Horsten HH. Sperm maturation in the epididymis. In: Carrell DT (eds). The Genetics of Male Infertility. Humana Press. DOI: https://doi.org/10.1007/978-1-59745-176-5_13.
9. Dacheux JL, Dacheux F. New insights into epididymal function in relation to sperm maturation. Reproduction 2013;147(2):R27–R42. DOI: 10.1530/REP-13-0420.
10. de Rooij DG, Grootegoed JA. Spermatogonial stem cells. Curr Opin Cell Biol 1998;10(6):694–701. DOI: 10.1016/s0955-0674(98)80109-9.
11. Devoto L, Fuentes A, Kohen P, et al. The human corpus luteum: Life cycle and function in natural cycles Fertil Steril 2009;92(3):1067–1079. DOI: 10.1016/j.fertnstert.2008.07.1745.
12. Ding N, Liu X, Jian Q, et al. Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2017;218:92–98. DOI: 10.1016/j.ejogrb.2017.09.004.
13. Drummond AE. The role of steroids in follicular growth. Reprod Biol Endocrinol 2006;4:16. DOI: 10.1186/1477-7827-4-16.
14. Ebner T, Moser M, Shebl O, et al. Prognosis of oocytes showing aggregation of smooth endoplasmic reticulum. Reprod Biomed Online 2008;16(1):113–118. DOI: 10.1016/s1472-6483(10)60563-9.
15. Ebner T, Moser M, Shebl O, et al. Developmental fate of ovoid oocytes. Hum Reprod 2008;23(1):62–66. DOI: 10.1093/humrep/dem280.
16. Esfandiari N, Burjaq H, Gotlieb L, et al. Brown oocytes: implications for assisted reproductive technology. Fertil Sterility 2006; 86(5):1522–1525.DOI: 10.1016/j.fertnstert.2006.03.056.
17. Farhi J, Nahum H, Weissman A, et al. Coarse granulation in the perivitelline space and IVF-ICSI outcome. J Assist Reprod Genet 200219(12):545–549. DOI: 10.1023/a:1021243530358.
18. Farquhar C, Rombauts L, Kremer JA, et al. Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Database Syst Rev 2017;5(5):CD006109. DOI: 10.1002/14651858.
19. Zanetti BF, de Almeida Ferreira Braga DP, Setti AS, et al. Is perivitelline space morphology of the oocyte associated with pregnancy outcome in intracytoplasmic sperm injection cycles? Eur J Obstet Gynecol Reprod Biol 2018;231:225–229. DOI: 10.1016/j.ejogrb.2018.10.053.
20. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: A committee opinion. Fertil Steril 2015;103(3):e18–e25. DOI: 10.1016/j.fertnstert.2014.12.103.
21. Ga R, Muvvala SPR. Access to infertility care and ART treatment in India: A clinician’s perspective. Best Pract Res Clin Obstet Gynaecol 2023;86:102302. DOI: 10.1016/j.bpobgyn.2022.102302.
22. Gardner DK, Schoolcraft WB. In vitro culture of human blastocysts. In: Jansen RP, Mortimer D, editors. Towards Reproductive Certainty: Infertility and Genetics Beyond. Carnforth: Parthenon Press; 1999, pp. 207–222.
23. Gnoth C, Godehardt E, Frank–Herrmann P, et al. Definition and prevalence of subfertility and infertility. Hum Reprod 2005; 20(5):1144–1147.DOI: 10.1093/humrep/deh870.
24. Yeung CH, Cooper TG, Oberpenning F, et al. Changes in movement characteristics of human spermatozoa along the length of the epididymis. Bio Repro 1993;49(2):274–280. DOI: 10.1095/biolreprod49.2.274.
25. Griesinger G, Diedrich K, Devroey P, et al. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: A systematic review and meta-analysis. Hum Reprod Update 2006;12:159–168. DOI: 10.1093/humupd/dmi045.
26. Haahr T, Roque M, Esteves SC, et al. GnRH agonist trigger and LH activity luteal phase support versus hCG trigger and conventional luteal phase support in fresh embryo transfer IVF/ICSI cycles: A systematic PRISMA review and meta-analysis. Front Endocrinol (Lausanne) 2017;8:116. DOI: 10.3389/fendo.2017.00116.
27. Handel MA, Schimenti JC. Genetics of mammalian meiosis: Regulation, dynamics and impact on fertility. Nat Rev Genet 2010;11(12):124–136. DOI: 10.1038/nrg2723.
28. Hassa H, Aydın Y, Taplamacıoğlu F. The role of perivitelline space abnormalities of oocytes in the developmental potential of embryos. J Turk Ger Gynecol Assoc 2014;15(3):161–163. DOI: 10.5152/jtgga.2014.13091.
29. Hassan-Ali H, Hisham-Saleh A, El-Gezeiry D, et al. Perivitelline space granularity: A sign of human menopausal gonadotrophin overdose in intracytoplasmic sperm injection. Hum Reprod 1998;13(12):3425–3430. DOI: 10.1093/humrep/13.12.3425.
30. Hirshfiel AN. Development of follicles in the mammalian ovary. Int Rev Cytol 1991;124:43–101. DOI: 10.1016/s0074-7696(08)61524-7.
31. Huckins C. The spermatogonial stem cell population in adult rats: I. Their morphology, proliferation and maturation. 1971;169(3):533–557. DOI: 10.1002/ar.1091690306.
32. Inhorn MC, Patrizio P. Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update 2015;21(4):411–426. DOI: 10.1093/humupd/dmv016.
33. Jiang Y, Song G, Yuan J, et al. ICSI with All Oocytes Recurrent Metaphase I Characterized by Absence Perivitelline Space. Open J Obstetr Gynecol 2012;11(9):1112–1116. DOI: 10.4236/ojog.2021.119104.
34. Kovačič B, Vlaisavljević V, Reljič M, et al. Developmental capacity of different morphological types of day 5 human morulae and blastocysts. Reprod BioMed Online 2004;8:687–694. DOI: 10.1016/s1472-6483(10)61650-1.
35. Lambalk CB, Banga FR, Huirne JA, et al. GnRH antagonist versus long agonist protocols in IVF: A systematic review and meta-analysis accounting for patient type. Hum Reprod Update 2017;23(5):560–579. DOI: 10.1093/humupd/dmx017.
36. Lasiene K, Vitkus A, Valanciūte A, et al. Morphological criteria of oocyte quality. Medicina (Kaunas) 2009;45(7):509–515. PMID: 19667744.
37. Lazzaroni–Tealdi E, Barad DH, Albertini DF, et al. Oocyte scoring enhances embryo-scoring in predicting pregnancy chances with IVF where It counts most. PLoS One 2015;10(12):e0143632. DOI: 10.1371/journal.pone.0143632.
38. Ledan E, Lacoste N, Heyman Y. Meiotic maturation of the mouse oocyte requires an equilibrium between cyclin B synthesis and degradation. Dev Biol 2001;232(2):400–413. DOI: 10.1006/dbio.2001.0188.
39. Li M, Ma SY, Yang HJ, et al. Pregnancy with oocytes characterized by narrow perivitelline space and heterogeneous zona pellucida: Is intracytoplasmic sperm injection necessary? J Assist Reprod Genet 2014; 31(3):285–294.DOI: 10.1007/s10815-013-0169-9.
40. Bartolacci AM, Intra G, Coticchio G, et al. Does morphological assessment predict oocyte developmental competence? A systematic review and proposed score. J Assist Reprod Genet 2022;39: 3–17. DOI: https://doi.org/10.1007/s10815-021-02370-3.
41. Mann T, Lutwak-Mann C. Male Reproductive function and semen, Springer, Berlin, 1981.
42. Matzuk MM, Lamb BD, DeMayo FJ. Small-molecule inhibition of BRDT for male contraception. Cell 2012;150:673–684. DOI: 10.1016/j.cell.2012.06.045.
43. Mortimer ST. Corner CASA—Practical Aspects2000;21(4):514–524. PMID: 10901437.
44. O’Donnell L. Mechanisms of spermiogenesis and spermiation and how they are disturbed. Spermatogenesis 2015;4(2): e979623. DOI: 10.4161/21565562.2014.979623.
45. Ovarian Stimulation TEGGO, Bosch E, Broer S, ESHRE guideline: Ovarian stimulation for IVF/ICSI. Hum Reprod Open 2020;2020(2):hoaa009. DOI: 10.1093/hropen/hoaa009.
46. Yu EJ, Ahn H, Lee JM, et al. Fertilization and embryo quality of mature oocytes with specific morphological abnormalities. Clin Exp Reprod Med 2015; 42(4):156–162.DOI: 10.5653/cerm.2015.42.4.156.
47. Pankaj Talwar. Jaypee’s Video Atlas of Assisted Reproductive Technologies and Clinical Embryology. New Delhi: Jaypee Brothers Medical Publication; 2014.
48. Panzarino M, Depalo R, Garruti G, et al. Francesco Giorgino & Luigi Eustacchio Selvaggi (2011) Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles, Gynecological Endocrinology 27;11:880–884. DOI: 10.3109/09513590.2011.569600.
49. Pepling ME. From primordial germ cell to primordial follicle: Mammalian female germ cell development. Genesis 2006;44(12):622–632. DOI: 10.1002/dvg.20258.
50. Plachot M, Selva J, Wolf JP, et al. Consequences of oocyte dysmorphy on the fertilization rate and embryo development after intracytoplasmic sperm injection. A prospective multicenter study. Gynecol Obstet Fertil 2002;30(10):772–779. DOI: 10.1016/s1297-9589(02)00437-x.
51. Rao KA. Principle and Practice of Assisted reproductive Technology. New Delhi: Jaypee Brothers Medical Publication; 2014.
52. Rienzi L, Ubaldi FM, Iacobelli M, et al. Significance of metaphase II human oocyte morphology on ICSI outcome. Fertil Steril 2008;90(5):1692–1700. DOI: 10.1016/j.fertnstert.2007.09.024.
53. Rienzi L, Vajta G, Ubaldi F. Predictive value of oocyte morphology in human IVF: A systematic review of the literature. Hum Reprod Update 2011;17(1):34–45. DOI: https://doi.org/10.1093/humupd/dmq029.
54. Rosenbusch H, Rauch E, Wiklund J. The mediating role of entrepreneurial orientation in the task environment–performance relationship. J Business Venturing 2002:17(5):635–659.
55. Schiewe MC. An effective, simplified, and practical approach to intracytoplasmic sperm injection at multiple IVF centers. J Assist Reprod Genet 13(3):238–245. DOI: 10.1007/BF02065943.
56. Suarez SS, Pacey AA. Sperm transport in the female reproductive tract. Hum Reprod Update 2016;12(1):23–37. doi: 10.1093/humupd/dmi047.
57. Tarlatzis BC, Fauser BC, Kolibianikis EM, et al. GnRH antagonist in ovarian stimulation for IVF. Hum Reprod Update 2006;12(4):333–340. DOI: 10.1093/humupd/dml001.
58. Ebner T. Extracytoplasmic markers of human oocyte quality. J Mamm Ova Res 2009;6(1):18–25. DOI: 10.1274/jmor.26.18.
59. Van Royen E, Mangelschots K, De Neubourg D, et al. Characterization of a top quality embryo, a step towards single-embryo transfer. Hum Reprod 1999;14(12):3172–3178. DOI: 10.1093/humrep/14.12.3172.
60. Visconti PE, Lewis SE, Suarez SS. Sperm bioenergetics in a nutshell. Biol Reprod 2012;87(3):72. DOI: 10.1095/biolreprod.112.104109.
61. Wasilewski T, Łukaszewicz–Zając M, Wasilewska J, et al. Biochemistry of infertility. Clin Chim Acta 2020;508:185–190. DOI: 10.1016/j.cca.2020.05.039.
62. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen, 5th edition. Geneva: World Health Organization; 2010.
63. Xia P. Intracytoplasmic sperm injection: Correlation of oocyte grade based on polar body, perivitelline space and cytoplasmic inclusions with fertilization rate and embryo quality. Hum Reprod 1997;12(8):1750–1755. DOI: 10.1093/humrep/12.8.1750.
64. Yakin K, Balaban B, Isiklar A, et al. Oocyte dysmorphism is not associated with aneuploidy in the developing embryo. Fertil Steril 2007;88(4):811–816. DOI: 10.1016/j.fertnstert.2006.12.031.
65. Yanagimachi R, Yanagimachi M, Rogers BJ. Mammalian fertilization. In: Knobil and Neill’s Physiology of Reproduction, 4th edition. Philadelphia, PA: Elsevier; 2015, pp. 851–909.
66. Yu B, van Tol HTA, Stout TAE, et al. Cellular fragments in the perivitelline space are not a predictor of expanded blastocyst quality. Front Cell Dev Biol 2021;8:616801. DOI: 10.3389/fcell.2020.616801.
67. Zeleznik AJ. The physiology of follicle selection. Reprod Biol Endocrinol 2004;2(1):1–7. DOI: 10.1186/1477-7827-2-31.
68. Zuckerman S. The number of oocytes in the mature ovaries. Recent Prog Horm Res 1951;6:63–108. DOI: 10.1210/rphv/6.1.63.
________________________
© The Author(s). 2023 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.