microTESE – A cutting edge procedure for male infertility

Sperm production. Coloured scanning electron micrograph (SEM) of sperm cells (spermatozoa) in the seminiferous tubules of the testis. This is the site of spermatogenesis (sperm production). Sperm tails are very pale pink, sperm heads are pale pink

Sperm production. Colored scanning electron micrograph (SEM) of sperm cells (spermatozoa) in the seminiferous tubules of the testis. This is the site of spermatogenesis (sperm production). Sperm tails are very pale pink, sperm heads are pale pink

Many of the men seen in my practice for male infertility are azoospermic.  This means they have no measurable amount of sperm in their ejaculate. This is a significant issue for these men wanting to have a biological child. Approximately half of these men have Obstructive Azoospermia (OA). Their testes produce enough sperm, but a blockage exists in either the vas deferens or the epididymal tubules that prevent the transport of sperm from the testes to the tip of the penis. Sometimes the vas deferens and epididymal tubules are missing.  The remaining half of our azoospermic patients have Non-Obstructive Azoospermia (NOA).  Their vas deferens and tubules are clear and open, but the ability of their testes to produce sperm is impaired.

Medical interventions exist that enable many men with azoospermia to father their own biological children.  Blockages can be surgically removed, and sperm production can sometimes be improved with pharmacological treatments.  However, for most men with NOA and many with OA, the only avenue available for achieving a pregnancy with a partner is to have sperm surgically retrieved from the testes and then used in an assisted reproductive technology (ART) treatment protocol involving in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

What is TESE?

In conventional testicular sperm extraction (TESE), a small incision is made in the scrotum exposing the testes.  An incision is then made in one of the testes, through the tunica albuginea (protective outer covering of the testis) to expose its parenchymal (working) tissue.  Special care is taken to avoid blood vessels. Pressure is applied along the incision until tissue containing seminiferous tubules protrudes through the incision site.  This tissue is surgically removed and set aside for cryopreservation and/or immediate use in IVF/ICSI.  The procedure is then repeated on the other testis.

Seminiferous tubules are the site of spermatogenesis (sperm production). However, spermatogenesis is not uniform throughout the testes, and so at any given time, some seminiferous tubules will have much higher concentrations of sperm than others.  It is not possible to evaluate the degree of spermatogenesis in seminiferous tubules with the naked eye.  So a surgeon has no way of visually assessing the tissue he intends to extract during a TESE for the presence of sperm.  For men with OA this conundrum is usually not problematic. They produce plenty of sperm, so chances are quite good that testis tissue retrieved by conventional TESE will contain sufficient sperm for IVF/ICSI.  This is not the case however for men with NOA.  Because their ability to produce sperm is impaired, the sperm concentration in their seminiferous tubules can range from adequate in some tubules to non-existent in others. As a result, they run the very real risk of having testis tissue retrieved by conventional TESE that is devoid of sperm and therefore unsuitable for IVF/ICSI despite having sufficient sperm production in another portion of the testicle.

When sperm are not found in conventional TESEs, fertility specialists often counsel patients that no viable option exists to achieve a pregnancy with a partner. Patients are encouraged to start looking at sperm donors.  This is outdated advice given by professionals who are unfamiliar with microdissection testicular sperm extraction (micro TESE).

Left image: Seminiferous tubules with and without sperm as seen using an operating microscope (20x magnification).
Right image: Confirmation of this by fixing and staining the tissue shown on the left and viewed under higher power magnification (400x).

What is microTESE?

A microTESE is a very different, far more complex type of surgical sperm retrieval compared to a conventional TESE. It is performed by an experienced urologic surgeon, who is an expert in the use of an operating microscope. The surgeon is assisted by a team of laboratory andrologists (specialists in the laboratory techniques required to identify and extract sperm from testicular tissue). An incision is made in the scrotum exposing the testes. Thirty or more microscopic specimens containing seminiferous tubules are taken from multiple sites on each testis. Individual seminiferous tubules in each of these samples are examined in the operating room by the laboratory andrologist to determine the presence of sperm. Seminiferous tubules containing sperm are usually plumper, light yellow in color, and often situated close to blood vessels. The surgeon is thus able to extract only tissue with the best potential to contain sperm, which is key to the success of the procedure (1). Once the tissue has been extracted, the laboratory andrologist will further examine it to assess sperm quality (concentration, maturation, morphology).  The andrologist will also prepare the tissue for immediate use or cryopreservation.  Using this approach, the operating team can focus on sites that appear to yield the best sperm concentration and quality, ensuring that a sufficient quantity of the most “promising” tissue is extracted.  A microTESE typically takes several hours from the first incision to last suture. A conventional TESE is usually completed in under an hour.

MicroTESE offers several advantages over conventional TESE (2,3). Studies show that for men with NOA, sperm retrieval rates (SRR) by micro TESE are significantly higher than conventional TESE. “Sperm was recovered from those with hypospermatogenesis in 84% and 92.9% by conventional and microdissection TESE, respectively. In the case of maturation arrest, SRR was 27.3% and 36.4% respectively. In cases of Sertoli-cell-only syndrome (SCOS), the SRR was 6.2% and 26.9% respectively.”1 The use of an operating microscope minimizes the amount of tissue that is removed, as many microscopic specimens are taken rather than larger biopsies. The use of an operating microscope also enables the surgeon to avoid disrupting blood vessels, decreasing the likelihood of damaging vascularized areas of the testes. This minimizes trauma and the resulting loss of functionality, such as a decline in testosterone production.  Better retrieval rates enable andrologists to cryopreserve testicular tissue for later use. Using cryopreserved sperm eliminates the need for synchronizing egg and sperm retrievals. It also eliminates the trauma and potential tissue damage caused by multiple sperm retrievals.

There has been some debate over the use of fresh versus thawed sperm for ICSI (4).  Many fertility specialists believed better outcomes are achieved with fresh sperm, as cryopreservation damages both cell and acrosome membranes and increases the damage caused by sperm oxidative stress. However several recent studies refute this assumption.  A recent review of data from 224 studies focusing on men with NOA revealed no difference in fertilization and pregnancy rates with fresh versus cryopreserved sperm used for ICSI.

The Bottom Line

Microdissection testicular sperm retrieval is offering new hope to men with NOA. However, I am ending this blog on a cautionary note.  This is not a procedure that can be done by all urologic surgeons. It requires a highly skilled urologic surgeon who has extensive experience using an operating microscope and doing testicular sperm retrievals. In addition, it requires a fertility laboratory with experienced and well-trained staff. Together, the surgeon’s and laboratory’s skill and experience is key to the success of this procedure (5).

References

  1. Caroppo E, Colpi EM et al. The seminiferous tubule caliber pattern as evaluated at high magnification during microdissection testicular sperm extraction predicts sperm retrieval in patients with non-obstructive azoospermia. Andrology 2019; 7: 8-14
  2. Ghalayini IF, A-Ghazo M, et al. Clinical Comparison of Conventional Testicular Sperm Extraction and Microdissection Techniques for Non-Obstructive Azoospermia. J Clin Med Res. 2011; 3(3): 124-131.
  3. Ravissini PC, Azevedo M, et al. Success rate in ICSI treatment of men with non-obstructive azoospermia (NOA): a comparative study between TESE (testicular sperm extraction) and microdissection-TESE. Fertil Steril.  2008; 90: S382-S383.
  4. Ohlander S, Hotaling J, et al. Impact of fresh versus cryopreserved testicular sperm upon intracytoplasmic sperm injection pregnancy outcomes in men with azoospermia due to spermatogenic dysfunction: a meta-analysis.  Fertil Steril. 2014; 101(2): 344-349.
  5. Ishikawa T, Nose R, et al. Learning curves of microdissection testicular sperm extraction for nonobstructive azoospermia. Fertil Steril 2010; 94(3): 1008-1011.

Directed Donation: A Novel Treatment Option for Fertility

A little-known fertility option is Directed Donation.  I thought a brief overview would be appreciated by those seeking additional options. I have included links at the end for those looking for additional information. A Directed Donor is a man storing sperm for use by a known recipient with whom he is not sexually intimate. This is in contradistinction to an  Anonymous Donor who is a donor whose identity is unknown to the recipient or a male Client Depositor who is an individual who deposits reproductive tissue prior to intended or potential use in artificial insemination or assisted reproductive procedures performed on his regular sexual partner.

The recipient for a Directed Donor might be a woman without a male partner who would like to have a child with sperm from an individual she knows, a woman in a relationship with a male partner who is not able to produce sperm or a transgender female wanting to have a child with a female partner or surrogate.

There are several steps by which the Medical Director qualifies a directed donor for specimen use by a recipient. These steps are similar to those required for an anonymous donor. If the qualification is performed in NY State the Directed Donor must be found eligible by the Medical Director of the facility prior to collection of the first semen sample for processing and storage. Determination of Eligibility includes the following components:

  1. A physical examination of the Directed Donor, as well as blood testing for indications of sexually transmissible diseases.
  2. A complete medical history, both individual and family, including first-degree and second-degree relatives.
  3. Genetic testing for major genetic disorders in consultation with a geneticist.
  4. Psychological evaluation and counseling to access psychological risks and evaluate financial and emotional coercion.
  5. Evaluation of a semen specimen
  6. Written informed consent must be obtained, and discussion had with the Recipient, Recipient’s Partner (if any) and Directed Donor about the results of the evaluation and use of the specimens.

The cryopreserved specimens are then quarantined as required by state regulations. In New York State this is 6 months but can be waived by the Recipient after a discussion of the potential risks of doing so. In all non-traditional fertility options, it is always prudent to seek advice from your Physicians assisting you with your fertility treatment as well as your legal advisors.

If you have any questions, please contact us at 516-487-2700.

Links to NY State and Federal Regulations:

  1. NY State Department of Health Reproductive Tissue Banking Regulations
  2. FDA Code of Regulations Title 21

You can sign up for my Blog at Men’s Reproductive Health Blog

Fertility Preservation and Gender Transitioning: The Decision to Bank Sperm

The desire to have children is common among individuals transitioning with 38% of respondents of the National Transgender Discrimination Survey indicating they are parents1. A Belgium study surveyed 121 patients transitioning and found that 40% would want children and that half of these would like a biologic child2.  Also in this study, 77% of 101 transgender women wanted the professionals treating them to discuss fertility options with 51% stating that they would have cryopreserved sperm, or at least seriously considered this if it had been discussed.

The World Professional Organization for Transgender Health (WPATH, http://www.wpath.org) first developed the Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People in 1979. However, it wasn’t until 2011 that they introduced specifics on the Reproductive Health needs of transgender people3. In the current WPATH Standards (http://bit.ly/2msEoQl) they recommend that prior to the initiation of therapy fertility preservation options are discussed, even if the person is currently not interested in future fertility.

Ideally, sperm should be collected before hormones are prescribed. However, it is possible in male to female transitioning that stopping feminizing hormones might provide a window to retrieve sperm. Even in the individual who does not have sperm in the ejaculate, or cannot produce an ejaculate, the potential for sperm retrieval and banking is possible with other modalities. Testicular biopsy with banking of tissue excised during the procedure can be used for conception with in vitro fertilization (IVF) couple with single sperm injection (ICSI). In addition, a recent study4 found normal spermatogenesis in 24% of testes removed at the time of sex reassignment surgery for individuals on long term estrogen therapy.  This suggests that banking of testicular tissue may still be possible in 1/4 of patients treated with long term hormonal therapy.  However, it must be noted that 75% of patients treated with long term estrogen therapy did not have sperm in the ejaculate or on biopsy.

At one fertility clinic11 patients were referred for sperm banking between January 2010 and May 2014. Nine of these patients banked sperm for future potential use. During this 52 month period, 1 couple used the stored sperm, which resulted in a pregnancy. It should be noted, however, that the mean age of the patients preserving sperm was 26.5 years of age which might account for the low usage rate of the banked sperm during this study. What was interesting in this study is that there was an increase in yearly referrals to their clinic over the 4.3 years they collected data. However, they found that referrals remained low which they postulated was due to both cost of sperm banking as well as lack of awareness that fertility preservation was an option.

Unfortunately, the reproductive needs of transgender individuals are still largely unmet6. Hopefully, this will be changing as more health professionals provide much-needed information on reproductive health to individuals undergoing gender transition.

References:

  1. James SE, Herman JL, Rankin S, Keisling M, Mottet L, Anafi M. 2015 U.S. Transgender Survey. December 2016:1-302.
  2. De Sutter P, Kira K, Verschoor A, Hotimsky A. The Desire to Have Children and the Preservation of Fertility in Transsexual Women: a Survey. International Journal of …; 2002.
  3. Coleman E, Bockting W, Botzer M, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. International Journal of Transgenderism. 2012;13(4):165-232. doi:10.1080/15532739.2011.700873.
  4. Schneider F, Neuhaus N, Wistuba J, et al. Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS). The journal of sexual medicine. 2015;12(11):2190-2200. doi:10.1111/jsm.13022.
  5. Jones CA, Reiter L, Greenblatt E. Fertility preservation in transgender patients. International Journal of Transgenderism. 2016;17(2):76-82. doi:10.1080/15532739.2016.1153992.
  6. HUNGER S. Commentary: Transgender People Are Not That Different after All. Cambridge Quarterly of Healthcare Ethics. 2012;21(2):287-289. doi:10.1017/S0963180111000818.