Eight things to make IVF fail

What are the causes of IVF failure? Young patients usually get their IVF babies after 1~2 cycles. In the patients over 38 years or with low ovarian reserve, multiple IVF cycles are always necessary. Eight things are common in the patients over 38 years or AMH < 2 ng/ml.

Poor response	The follicles cannot be stimulated by external rFSH. It may result in the follicle atresia or growth arrest.
Premature ovulation	Ovulation in IVF generally occurs 36-40 hours after the triggering. Premature ovulation during IVF results in the cancellation of oocyte retrieval.
Empty follicle	Mostly one follicle contains one oocyte. It is found that there is no oocyte in a follicle after the retrieval.
Low oocyte yield	Only mature oocyte (MII) can be fertilized. Nearly 70% of the retrieval oocytes can be used for the following fertilization in the patients under 35 years; in those over 40 years, the yield is dropped down to 50% or even lower.
Low fertilization rate	The general fertilization rate (2PN) in IVF is around 70%, but it can be lower or complete fertilization failure.
Abnormal fertilization	Two pronuclear zygote (2PN) is observed after a normal fertilization. An abnormal fertilization happens while three pronuclei (3PN) or mutiple pronuclei are observed.
Developmental arrest	Around 95% of 2PN zygotes grow into the cleavage stage. Developmental arrest could happen at any time point during embryo mitosis, e.g. one-cell arrest, 2-4 cells arrest, 6-8 cells arrest, arrest at compaction stage...etc.
Low blastocyst formation rate	After five days of culturing, an embryo undergoes cell proliferation and differentiation to become a blastocyst. No blastocyst formed or no blastocyst with good morphology formed at the end of culturing happened in IVF sometimes.

What can we do to the eight things?

Poor response	Individualizing stimulation protocol by adjusting with maternal age is a method, such as mild stimulation, natural cycle, or multiple retrievals in a IVF cycle.
Premature ovulation	Individualizing the time of triggering and retrieval by adjusting with maternal age, follicle size, and total follicle count. Non-steroid anti-inflammatory drugs (NSAIDs), which was reported to prevent premature ovulation in the previous data, can be applied 8~14 hours before the retrieval as well. For an example, the trigger shot may be injected while the follicle reaches to 17 mm in diameter to the patients under 40 years, but it may be injected while the follicle reaches to 15~17 mm in diameter to those over 40 years to prevent the premature ovulation.
Empty follicle	It cannot be avoid if the empty follicle forms naturally.
Low oocyte yield	The patient can undergo multiple IVF cycles to harvest available oocytes (oocyte accumulation).
Low fertilization rate	The quality of sperm and oocyte could be the reasons. The ICSI/IMSI can be applied to select the sperm with better morphology. Of the quality of oocyte, it cannot be solved due to the effect of maternal age.
Abnormal fertilization	If it resulted in abnormal fertilization (3PN or multiple PNs) while the ICSI/IMSI had been applied, the quality of oocyte could be the main reason. Oocyte accumulation by multiple IVFs is the only solution.
Developmental arrest and Low blastocyst formation rate	Similarly, developmental arrest or no available blastocyst formed during culturing occurs spontaneously and cannot be avoid. Embryo accumulation by multiple IVFs is the only solution.