Azoospermia


Azoospermia

There are some men suffering from sterility due to the lack of spermatozoa in the ejaculate. This is called azoospermia.

There are two kinds of azoospermia: obstructive azoospermia or non-secretory, and non-obstructive azoospermia or secretory.

Obstructive azoospermia: they are men having very injured seminal tract, with deferents agenesia and/or epididymis and epididymis obstructions. They do not have spermatozoa in the ejaculate, but these spermatozoa can be found in epididymis and testicle. The only treatment we can follow in this case is to make epididymis spermatozoa aspiration (MESA) or a testicular biopsy (TESE) to obtain spermatozoa and inject them inside the egg (ICSI).

Non-obstructive or secretory azoospermia: they are men having problems with sperm production; there are spermatozoa neither in the ejaculate, nor in the testicles. Depending on which level the sperm development is blocked, we will find different germinal cells, spermatogonium, spermatocyte and spermatids, which are immature cells. In some cases there are not these immature cells, and there are only Sertoli cells.

INDICATIONS
Obstructive azoospermia.
Non-obstructive azoospermia.

METODOLOGY
A testicular biopsy will be performed if testicular spermatozoa are needed to obtain fertilization (TESE). Only spermatids or immature sperm cells injection is performed in the egg (ROSI or ELSI) when there are spermatozoa neither in the ejaculate nor in the testicular biopsy. If that is the case, testicular biopsies will be treated in vitro culture inside the correct conditions, to obtain spermatozoa or sperm forms as much developed as possible.
All this is known by the couple and they give their consent. You have at your disposal information sheets about all techniques. There are also sheets for the couple to give their consent and accept what they are asking for.
The proofs show that secretory azoospermia is caused by the lack of spermatozoa production in the testicles. Nonetheless, sperm has live germ immature cells and with no apparent problems. So, it would be possible to obtain the development of these cells to spermatids state by cellular culture. These spermatids developed in the culture would be injected directly in the egg to fertilize it.
A testicular biopsy is needed for this technique to success, because other types of testicular cells, absent in the ejaculate but present in the testicular tissue, are needed to help germ cells to develop into the in vitro culture.
This technique has provided the birth of some babies with normal genes. Analysis and treatment to the patient will be the same as the ones followed to perform ICSI with spermatozoa in the ejaculate.
The number of babies born by spermatids injection, mainly developed spermatids in vitro, is very low. So we advise you to ask for prenatal diagnosis, once the pregnancy has begun. You will need to perform an amniocentesis to analyze chromosomes and one ultrasound scan to study the foetus morphology.

In vitro culture of testicular biopsy.
Once the testicular tissue has been obtained following testicular biopsy and mechanical disintegration of seminiferous tubules, meiotic maturation of human germ cells is performed following in vitro culture in the presence of recombinant follicle stimulating hormone (rFSH) and testosterone, for 24 or 48 hours in 86 F (30 ºC) and 5% of CO2.
Meiotic arrest (mainly inside primary spermatocyte phase) is the most common block kind in sperm maturation, in men with non-obstructive azoospermia. There is a recent new perspective due to the discovery to avoid meiotic arrest in vivo after in vitro maturation. Another treatment based on meiotic reduction of primary spermatocyte after egg microinjection (proved in mice) may cause a high risk of chromosome abnormalities due to premature segregation of sister chromatid.
If post-meiotic maturity arrest appears, (spermiogenesis failure), in vitro culture may be beneficial, because elongated spermatids are formed with no apoptotic DNA damage, when compared with round spermatids before in vitro culture. This is important because germ cells apoptosis may be main obstacle to assisted reproduction using spermatids when there is a complete block of spermiogenesis. In fact, in vitro culture application provided first healthy babies births, when there was a total spermiogenesis failure.
From the clinical point of view, a very important fact is reached following this technique:

  • The couple do not need to ask for at semen bank to have children.
  • To maintain the genes information of the patient, which would maintain genotype characteristics in the eventual embryo.

FERTILIZATION

Fertilization will be studied 24 hours after follicular puncture. At this moment, patients are informed about the number and quality of fertilized eggs (zygotes).
Not all zygotes reach the pre-embryo stage, so this is just to inform the couple.
48 o 72 hours after follicular puncture, one or three obtained pre-embryos and best quality ones are transferred into the patient’s womb. It is demonstrated that this number of pre-embryos produces more possibilities of getting pregnant and less possibilities of multiple pregnancy.

Non-transferred pre-embryos are frozen, after been accepted and known by the couple. These embryos can be stored for the couple for a maximum period of five years, and after that period the Clinic becomes the owner, in case the couple do not ask for them. Patients that do not need these embryos will donate them to the Clinic to the embryo donation protocol. This protocol is useful for couples with unsuccessful assisted reproduction tries due to bad quality male and female gametes producing non-evolutionary embryos.

A big quantity of embryos can be obtained after fertilization drugs to ovarian stimulation. Eggs may be donated to women with problems to produce their own eggs when there is a high number of them. Nonetheless, donor maintains a number of her own eggs enough to be transferred, and to be frozen with her consent. Donation is unknown and free, an it is also beneficial both for recipients and donors, because putting together their eggs with different spermatozoa provide important information.

  • The problem is related with spermatozoa if fertilization fails with semen of her own partner but success with semen of another men.
  • The problem is in the eggs when fertilization fails in both cases.
  • If there is a good fertilization with different semen samples, as it is the rule, data about embryos quality, womb receptiveness, etc, are obtained.

There is also a protocol of pure egg donor. Eggs are obtained from a woman donating her eggs to women suffering from infertility, due to lack or bad quality eggs, and who want to have children. If this is the case, there are two different protocols. If the patient is not capable of producing her own eggs, donor eggs will be fertilized with the semen of the male partner. Resulted embryos will be transferred to the patient, in a number assuring pregnancy. Non-transferred embryos will be frozen. In this case, obtained embryos have half the genetic information from the donor and half from the patient’s partner.

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