Embryology Q&A

Embryology Q&A by Sule Dogan PhD HCLD/ CC (ABB)

Q: What is the fertilization success rates with ICSI and why do not all eggs get fertilized with ICSI?

A: The overall fertilization rate should be more than 80% in an ICSI cycle, but this rate is higher if any donor oocytes are used in the cycle, or it might be lower depending upon the patient profile. There might be many reasons for fertilization failure in an IVF /ICSI cycle. Two main reasons would be the oocyte maturation abnormalities that are negatively affected by maternal age and suboptimal semen parameters such as non-obstructive azoospermia and sperm morphological defects. It is very rare, but sometimes (1-3 % of ICSI cycles and 5-10% of IVF cycles) none of the mature oocytes get fertilized after IVF/ ICSI, this phenomenon is called total fertilization failure (TFF). Fertilization failure might be caused by oocytes activation deficiency (OAD) where oocyte activation is failed due to certain mutation in either sperm or oocyte. Some of those well-known mutations are phospholipase C zeta (PLCζ), PLCZ1 mutations, wee1-like protein kinase 2 (WEE2) mutations, PAT1 homolog 2 (PATL2) mutations, tubulin beta-8 chain (TUBB8) mutations, and transducin-like enhancer protein 6 (TLE6) mutations.

Q: How common are Day 6 or 7 blastocysts? Can they still produce a successful outcome?

A: Preimplantation genetic testing for aneuploidy (PGT-A) screens embryos for numerical chromosomal abnormalities. Genetically tested embryos have a better chance of implantation capability compared to not tested embryos. Although clinical pregnancy is lower with the Day 7 blastocyst (13.9%) in non-PGT cycles, this goes up to 41.7% when an Euploid Day 7 blastocyst is transferred. Recent studies showed that pregnancy rates are comparable with Day 5 and Day 6 blastocysts in PGT cycles. Clinical outcomes are affected by patient age, BMI, endometrial thickness, and embryo’s inner cell mass grading (ICM) rather than biopsy day. In non-PGT cycles, the data support the selection of day 5 blastocysts for transfer over day 6 blastocysts.

Q: Is there anything that can help get PGTA normal embryos after multiple rounds without success?

A: Preimplantation genetic testing for aneuploidy (PGT-A) only screens embryos for numerical chromosomal abnormalities. According to the current literature, Euploidy rate in embryos is positively related to AMH levels and negatively related to female age. Using microfluid sperm sorting or PICSI dish with hyaluronic acid binding assay to improve Euploidy rates is still controversial. However, these methods may be used for cases with severe male factor infertility or advanced paternal age as an alternative. Donor oocytes may be another alternative to achieve pregnancy in cases with previous multiple IVF failures.

Q: What is the difference between PICSI and Zymot?

A: Both PICSI and Zymot are sperm selection devices in IVF/ICSI cycles. PICSI is a dish with Hyaluronan microdots where mature sperm will bind to hyaluronan so that they can be selected and used for ICSI. Zymot is a microfluidic device that sorts motile and morphologically normal sperm from a raw sample without centrifugation.

Although there are studies supporting clinical use of both devices in IVF / ICSI cycles, the current literature is controversial if these devices improve the pregnancy outcome while they increase the cost of a cycle. According to a study, both fertilization rates and transfer eligible embryo rates were significantly higher in PICSI fertilized oocytes compared to their ICSI counterparts. However, another study found that there were no statistically significant differences between ICSI vs PICSI groups in clinical pregnancy rates. Based on the findings of a study, Zymot decreased sperm DNA fragmentation and increased the implantation and clinical pregnancy rates. Contrarily, Molly et al., showed that there were no differences found in the clinical pregnancy or ongoing pregnancy rates between Zymot vs routine sperm selection method.

Q: How to improve getting healthy embryos with MFI?

Male factor infertility (MFI) is responsible for 30% to 50% of all cases of infertility. Male infertility may be caused by endocrine, physiological and testicular disorders as well as, environmental and genetic problems. Male infertility can also be classified as pre-testicular, testicular and post-testicular. Male infertility can be diagnosed by semen analysis where sperm parameters are evaluated and other tests such as hormonal tests and genetic tests. Based on the cause of male infertility, clinicians may be able to treat the underlying cause. The most common assisted reproductive technologies to treat male infertility is intracytoplasmic sperm injection (ICSI). Another procedure for male factor infertility patients is to retrieve sperm surgically via testicular sperm aspiration (TESA) if there is no sperm in the semen.  Depending upon the cause of infertility, preimplantation genetic testing for Aneuploidy (PGT-A) can be included in the treatment plan to have genetically normal (healthy) embryos for transfer. The recent guideline published by American Urological Association (AUA) and American Society for Reproductive Medicine (ASRM) outlines the management and treatment of male infertility in IVF/ICSI cycles for clinicians.

Q: Is 3 flagged genetic diseases in a carrier screening test worring for embryos normality?

A: It depends on the genetic diseases that are flagged in the carrier screening. Genetic diseases may or may not be a risk factor in pregnancy and in embryo development. We know that some genetic diseases or mutations can be lethal when inherited while some do not impact embryo development. The American College of Obstetricians and Gynecologists (ACOG) recommends that carries screening for Spinal Muscular Atrophy and Cystic Fibrosis should be offered to all women who are considering pregnancy or currently pregnant. If any of the patients are carriers of any genetic diseases, then preimplantation genetic testing for monogenic diseases (PGT-M) should be discussed. Genetically normal i.e., Euploid and Unaffected embryos can be detected by using PGT-M technology in IVF/ICSI cycles where a few cells are biopsied from an embryo and tested for a specific gene disease by using next-gene sequencing (NGS) technologies. This PGT-M technique has been successfully used for sickle cell disease and most types of β-thalassemia patients. It is strongly recommended to get genetic counseling regarding the risks of those flagged genetic diseases.

Q: Can TESE be a solution for couples who have a problem getting embryos to blastocyst?

A: Yes and No! Blastocyst formation is affected by many factors such as oocyte related issues and sperm related problems. Testicular sperm aspiration has been successfully used in men with both obstructive and non-obstructive azoospermia for many years. Studies showed that the clinical outcomes, including fertilization and blastocyst rates are comparable between ICSI cycles using testicular and ejaculated sperm. In 2013, another study suggested that the ICSI cycles with testicular sperm have better fertilization and pregnancy rates compared to the ones with ejaculated sperm when the embryo transfers were done on Day 3. However, a latest study published in 2021 showed that using testicular sperm over ejaculated sperm in patients with non-azoospermia such as patients with low sperm concentration (oligozoospermia) did not improve fertilization, blastocyst, miscarriage and live birth rates.

Q: How long does schooling for this take?

A: Embryology is a very unique field where both reproductive biology and clinical lab sciences meet. Embryologists work with physicians, nurses and patients closely on a daily basis. Although there are master’s programs in clinical embryology, these programs offer limited hands-on experience. Embryologists usually enhance their skills during their orientation in fertility clinics over the years or attend training programs by private companies or workshops and conferences by the American society of reproductive medicine (ASRM). To work as an Embryologist, one must have to obtain a minimum of a bachelor’s degree in medical, laboratory and life sciences and a minimum of three to four years of clinical IVF laboratory experience or a master’s degree in Reproductive Science and two years of IVF lab experience or PhD degree in biological and reproductive sciences and a year of IVF lab experience. Some states require licensing and certification, which are similar to medical technologist or medical laboratory scientists certifications.

There are online master’s and PhD programs by Eastern Virginia Medical School. https://www.evms.edu/education/masters_programs/reproductive_clinical_science_masters_program/

There are also hands-on certificate courses by private companies such as ART lab, IVF Academy USA, Ovatools, and WEST.

References

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