Androlog of the Fertility and Sterility Dialog

Feb 04, 2022

Is the term ‘Non-Male Factor’ evidence-based?

We read the recent systematic review in F and S Reviews by Bantel- Finet et al.1 with dismay.  This is the latest in twenty years of such reviews reinforcing the concept that among couples with non-male factor infertility; defined primarily based on routine semen analysis, ICSI is no more successful than IVF. We believe that this concept is fundamentally flawed. Since IVF began in 1978, the standard male fertility workup has been a semen analysis alone. This has proved to be inadequate with up to a third of men being diagnosed with unexplained infertility2. In current practice, couples with ‘unexplained’ infertility are given IVF as the first option with no further investigation of the male partner. This is despite our knowledge that 25-30% of infertile men have palpable varicoceles; treatment of which improves their fertility3 and 20% of whom have asymptomatic but treatable infections4. It is a matter of great disappointment that we, as a speciality, have made so little progress in 40 years, despite all the advanced andrological tests now at our disposal. Even the nomenclature of ‘male factor’ has a pejorative connotation.  According to this classification, all men have only ‘one factor’ causing their infertility. In contrast, we are delighted to see the major learned societies are changing their views. Last year, when WHO published their laboratory manual for examination of human semen 2021:  Sperm DNA testing has been added as an extended test. In their words ‘The evaluation of sperm DNA testing could constitute an important addition of male infertility, becoming one of the most discussed promising biomarkers in basic and clinical andrology. Further, ASRM/AUA and EAU have revised their guidelines to include further investigations of both the man and his sperm for unexplained infertility, failed ART, and recurrent pregnancy loss (RPL).  ESHRE guidelines for RPL have also been updated to report its association with sperm DNA although none has been observed with semen analysis. Finally, we need to consider the global cost of ignoring male reproductive health. Recent data indicate that infertile men have an increased risk of somatic disorders such as cancer and die younger than fertile men. Prof Chris Barratt has led a welcome global initiative, but government funding for such research has been pitiful, showing a lack of concern for men and their ongoing health.  Prevarication until we have more evidence, more initiatives, more time in clinic is indefensible We must start now to provide adequate male fertility care and take to heart the immortal words ‘Perfection is the Enemy of Progress’. Sheena E M Lewis1,2, Honorary Professor1, Queen’s University of Belfast, UK  CEO2 Examenlab Ltd, Unit 18A, Block K, Weavers Court Business Park, Linfield Road, Belfast BT12 5GH, Email    Sandro C. Esteves ANDROFERT, Andrology and Human Reproduction Clinic and Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, SP, Brazil Email:    References De Bantel-Finet A et al. Does intracytoplasmic sperm injection improve live birth rate when compared with conventional in vitro fertilization in non-male factor infertility? A systematic review and meta-analysis. Fertil Steril Rev Vol. 3, No. 1, January 2022  Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012 Sep-Oct;38(5):576-94. doi: 10.1590/s1677-55382012000500002.   3. Birowo et al. The benefits of varicocele repair for achieving pregnancy in male infertility: A systematic review and meta-analysis. Heliyon. 2020 Nov 5;6(11):e05439. doi: 10.1016/j.heliyon.2020.e05439. eCollection 2020 Nov.  4. Boeri L, Salonia A et al. Semen infections in men with primary infertility in the real-life setting Fertility and Sterility Volume 113, Issue 6, June 2020, Pages 1174-1182
Oct 12, 2020

hCG for hypo-hypo men

Ive always been confused by how hCG can successfully stimulate spermatogenesis in some hypogonadotropic hypogonadal men.  I get that it should raised leydig cell T production via the LH receptor, but without FSH to stimulate ABP from sertoli cells, how does the T stay in the seminiferous tubules to promotes spermatogenesis?  

Pioneer in male reproduction

To All:   It is with sadness that I report the death of Dr. Richard Amelar. Dr. Almelar’s name may not be familiar to fellows trained in male reproduction in recent years,  but he was the first urologist to truly confine his entire practice to the study and treatment of male reproduction. He and his partner, Dr. Larry Dubin, were the first to call attention to the absence of fructose from the semen along with the unusually low volume of semen in men with bilateral congenital absence of the vas deferens. Along with Robert Hotchkiss, Ph.D., Dr. Amelar helped develop  the histologic classification of testicular biopsies that still is used. Drs. Amelar and Dubin popularized varicocelectomy for the treatment of male infertility. They also were the donors of their silver sperm lapel pin that they gave to many of us who now are older urologists interested in male reproduction. Whatever Dr. Amelar may have said or written always could be trusted to be precisely what his careful studies had revealed. He was a source of inspiration to many of us, who remember him for his kindness and contributions to the field of male reproduction. Arnold Belker, MD Clinical Professor Emeritus Department of Urology University of Louisville School of Medicine Louisville, Kentucky 40202
Jul 29, 2020

Low volume oligospermia

I have a problem patient. 38 year old male with 2ndary infertility. History of acoustic neuroma 2018. Recent SA revealed volume 0.21 cc ( didn’t miss) concentration 5.18 million/cc TMC 9.46. Zero percent motile. pH 6.4. Hormone profile WNL. Has Gr111 varicocele. With the low pH, I was wondering about EDO and a cyst but TRUS showed nothing. Am awaiting the second SA. Labs temporarily closed still. Any other things I may be missing?  So far it has been suggested on Twitter to perm a post ejaculatory urine and to consider a partial EDO and perform a TURED. Any other suggestions?
Apr 19, 2020

Semen osmolality in vitrp

We started to investigate what happens with osmolality in semen in vitro and possible effects on sperm function. Or Ph.D. student, Emma Holmes, now has finished her doctoral thesis on the topic. Due the ongoing pandemic, Karolinska institutet in Stockholm, Sweden has supported the use of web-formats for both public defense and dissemination of the thesis itself. Thus, anyone interested should be able to download the Thesis: On Osmolality and Sperm Function During Processing for Assisted Reproduction at ANOVA, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.ABSTRACT Deep basic knowledge about sperm physiology is relevant and important to optimize the outcome of procedures used during Assisted Reproductive Technologies (ART) to select spermatozoa for fertilization. More specifically, this study examined osmolality changes and consequences for sperm motility and sperm selection in the laboratory. What kind of environmental changes occur and what challenges must the spermatozoa endure after leaving the body? How do these challenges affect the spermatozoa’s functions, fertilizing potential and the make-up of the genetic material they will deliver to the oocyte?In study I, the objective was to measure the changes in osmolality that occur after collecting the ejaculate in the laboratory. After ejaculation, the sample is mixed in order to make it homogenous. This will cause the different fractions that make up the semen sample to mix.  A total of 348 individual ejaculates, 5 split ejaculates and 6 ejaculate pools were studied, and it appeared that there was an individual pattern of change in osmolality over time. At 3 hours after the ejaculation, the change in osmolality ranged from 2 mOsm/kg to 164 mOsm/kg. Furthermore, it was evident that the change in osmolality was temperature dependent. Samples stored at 37°C increased significantly more in osmolality than samples stored at 1822°C, than samples stored at 4-7°C and than samples stored at -20°C. Denaturising temperature (100°C) blocked any further increment in osmolality. One probable cause of the increase in osmolality is that the enzymes, which are abundant in the prostatic fluid, are degrading macro-molecules, such as the proteins that are abundant in the seminal vesicular fluid. When these two secretions are mixed, the enzymatic degradation can start (Mann and Lutwak–Mann, 1981).In study II, the markers for the different fractions of the ejaculate were measured in order to relate to the change in osmolality. As well as containing high levels of proteins, the seminal vesicular fluid also contains relatively high levels of fructose. Similarly, the prostatic fluid contains high levels of zinc. It was shown that 19% of the variation in semen osmolality covaried with the relative contribution of the prostatic fluid marker, zinc, and the seminal vesicular marker, fructose, while the epididymal marker neutral α-glucosidase did not covary. Furthermore, the results show that after removing sperm from the ejaculate, the osmolality still increased, thus, the sperm did not have an effect on the increase. In addition to the challenge of the osmotic increase occurring in the ejaculate, the preparation of the sperm for ART presents yet another challenge. Most commercial sperm preparation media, such as density gradients or swim-up media have an adjusted osmolality of 290300mosm/kg. Thus, depending on the individual increase in osmolality of the samples, the sperm will be exposed to varying sudden decreases in osmolality during preparation. In study III and IV, it was examined how a hypo-osmotic challenge could affect sperm motility and the outcome of sperm selection when using density gradient centrifugation. Sperm motility was assessed by Computer Assisted Sperm Analysis (CASA). When the spermatozoon was exposed to a sudden decrease in osmolality, it took up water and swelled,causing the tail to coil and fold. This in turn, resulted in a decreased motility (VCL) with as much as 20%. Furthermore, it appears that the greater the decrease in osmolality, the lower the yield was after selection of spermatozoa by density gradient centrifugation. In contrast, with further investigation, it was shown that the DNA-Fragmentation-Index (DFI), measured by flow cytometry of acridine-orange stained spermatozoa was not affected by longer incubation times. However, spermatozoa ejaculated directly into a buffer had lower values for DFI% compared to samples diluted with buffer shortly after ejaculation.The negative effect on the yield was eliminated when the ejaculate was diluted soon after ejaculation or collected directly in a buffered solution.Since the increase in osmolality in vitro is so variable, one standardized procedure for sperm preparation would not work for all ejaculates. However, if increasing osmolality can be minimized by early dilution of all samples, then the negative effects can in large be eliminated.The thesis is accessible by this link Andrology Regards, Lars Björndahl, M.D. Ph.D.ANOVA - Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
Oct 18, 2019

Isodicentric Y Chromosome

I have a male with an isodicentric Y chromosome.  He is rare from what I can read, in that he is phenotypically male and has sperm in his ejaculate in the severe oligospermia range.  His blood karyotype shows his Y chromosome has 2 centromeres, 2 SRY regions, and duplication of the AZF regions.  I assume his gonadal karyotype must be similar and stable, given his male phenotype, descended testicles, and impaired but functional sperm production.He presented to us after multiple failed cycles overseas and we ordered the karyotype.  The question is, with PGT, would you transfer a male embryo?  In theory, the best case scenario would be his same Y chromosome.  But you would think due to the instability of duplicated centromeres, there would be a significant risk of mosacisim in the inner cell mass and gonadal cells, that could result in loss of some or all of the Y function, leading to either sex reversal or Turner syndrome in most of his male embryos.  Given the high risk of instability, a trophectoderm biopsy wouldn't be guaranteed to reflect the ICM and even knowning the ICM wouldn't guarantee the future gonadal cell line would not become mosaic.  So if he wanted a male offspring and you had PGT result that confirmed his same Y chromosome in the trophectoderm, would you allow transfer of that embryo?  Or would you only allow transfer of XX embryos? Anything else Im missing in thinking through this?  Im having a hard time finding a case report of anyone with isodicentric Y with adequate sperm production for use with ICSI.
Jan 15, 2019

follow up for 13 yo with pan-hypopit

I previously sent this out in the Fall and wanted to give some follow up.  I saw a 13 yr old boy with pan-hypopit.  He also had bilateral cryptorchidism with bilateral orchidopexy at age 6 months.  His exam demonstrates extremely small testes.  I had recommended that they start testosterone when appropriate; however, his mom belongs to some support group and had heard about HCG therapy and wanted to try it.  I started him on 2000 IU 3 times/week.  He had labs done after about 6 weeks of treatment with no response.  Is it worthwhile to continue the HCG, and if so, how much would you increase the dose?  Alternatively, should he just start testosterone, and then re-visit this when he is older?  Thanks.Jay
Dec 28, 2018

Sperm retrieval in advanced prostate cancer patient

I have a gentleman in his 50s with secondary infertility who was recently diagnosed last July with metastatic (visceral) prostate cancer  who is interested in IVF/ICSI.  I've only had a phone consultation with him, but he's been on docetaxel, bicalutamide, abiraterone, & prednisone. He has erectile dysfunction, doesn't ejaculate, and recently had a TURP,  I was planning on a diagnostic needle TESE, but the patient is very concerned about the potential for genetic defects attributable to the numerous agents he has received thus far for his prostate cancer. Thank you, Ernie Sussman, Las Vegas, NV
Mar 29, 2018

Androlog has moved! What do you think?

We started Androlog, an internet based email discussion forum for male reproductive medicine and biology, in 1994. Then, the World Wide Web was in its infancy. There were no smartphones, no social media, no high speed wireless. But the sheer force of the new availability to communicate worldwide questions and answers about andrology propelled Androlog forward, and by 2017, about 1700 members were talking to each other via email daily.But by then the infrastructure of Androlog had aged and was getting flaky. Plus, new communications devices like smartphones and tablets were in common use, and social media had changed the way we interact on the web. It was time for a change.Luckily we had just built out a social media platform for Fertility and Sterility, the Dialog, and here we are. We're asking our 1700 or so Androlog members to move our conversations here, and we think that it will be worth it. What do you think?

About this special feature

Androlog is a space for real-time conversations about male reproductive medicine.