Textbook Fundamentals of Male Infertility Sherman Silber Ebook All Chapter PDF

Fundamentals of Male Infertility
Sherman Silber
Visit to download the full and correct content document:
https://textbookfull.com/product/fundamentals-of-male-infertility-sherman-silber/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...
Male Infertility A Clinical Approach 1st Edition

Karthik Gunasekaran
https://textbookfull.com/product/male-infertility-a-clinical-
approach-1st-edition-karthik-gunasekaran/
Andrological Evaluation of Male Infertility A

Laboratory Guide 1st Edition Ashok Agarwal
https://textbookfull.com/product/andrological-evaluation-of-male-
infertility-a-laboratory-guide-1st-edition-ashok-agarwal/
Molecular Signaling in Spermatogenesis and Male

Infertility First Edition Rajender Singh
https://textbookfull.com/product/molecular-signaling-in-
spermatogenesis-and-male-infertility-first-edition-rajender-
singh/
Male Infertility in Reproductive Medicine: Diagnosis

and Management 1st Edition Botros Rizk (Editor)
https://textbookfull.com/product/male-infertility-in-
reproductive-medicine-diagnosis-and-management-1st-edition-
botros-rizk-editor/
The Boston IVF handbook of infertility Alper
https://textbookfull.com/product/the-boston-ivf-handbook-of-
infertility-alper/
A Compendium of Neuropsychological Tests: Fundamentals

of Neuropsychological Assessment and Test Reviews for
Clinical Practice 4th Edition Elisabeth M. S. Sherman
https://textbookfull.com/product/a-compendium-of-
neuropsychological-tests-fundamentals-of-neuropsychological-
assessment-and-test-reviews-for-clinical-practice-4th-edition-
elisabeth-m-s-sherman/
Male Rape is a Feminist Issue Feminism Governmentality

and Male Rape 2014th Edition Cohen
https://textbookfull.com/product/male-rape-is-a-feminist-issue-
feminism-governmentality-and-male-rape-2014th-edition-cohen/
Textbook of Male Genitourethral Reconstruction

Francisco E. Martins (Editor)
https://textbookfull.com/product/textbook-of-male-genitourethral-
reconstruction-francisco-e-martins-editor/
Infertility and Intimacy in an Online Community Paulina

Billett
https://textbookfull.com/product/infertility-and-intimacy-in-an-
online-community-paulina-billett/
Fundamentals of
Male Infertility
Sherman Silber, M.D.
123
Fundamentals of Male Infertility
Fundamentals of Male
Infertility
Sherman Silber, MD
Director, Infertility Center of St. Louis
St. Luke’s Hospital
St. Louis, MO, USA
Professor of Urology
University of Michigan
Ann Arbor, MI, USA
With Science Editor:

Dr. Yuting Fan, MD, PhD
Whitehead Institute
Massachusetts Institute of Technology
Cambridge, Massachusetts, USA
Sun Yat-sen University of Medical Sciences
Guangdong, China
Sherman Silber, MD
Director
Infertility Center of St. Louis
St. Louis, MO, USA
ISBN 978-3-319-76522-8 ISBN 978-3-319-76523-5 (eBook)

https://doi.org/10.1007/978-3-319-76523-5
Library of Congress Control Number: 2018941091
© Springer International Publishing AG, part of Springer Nature 2018

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, express or implied, with respect to the material contained herein or for any errors
or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims
in published maps and institutional affiliations.
Printed on acid-free paper
This Springer imprint is published by the registered company Springer Nature Switzerland AG.
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Foreword
It is always intriguing to write a foreword for a special groundbreaking book. It is

inspiring that this book deals in a clear no-nonsense way with the sometimes con-
troversial fundamentals of male infertility. In the past male infertility had been
vexed by specious treatments and even IVF was problematic. I have had yearly
transatlantic collaboration with Dr. S. Silber on this subject since 1979. We met
every year many times somewhere in the world to solve the problems of male infer-
tility. For 40 years we accomplished many advances in the field.
This book is fascinating because it honestly and clearly describes the science of
male infertility and all the possible treatments which have been proposed during
these last 40 years. The surprise of the book is that the reader will be guided into the
correct approach for every controversial issue. There are many myths in male infer-
tility. The crucial point of this book is to explain the science of male infertility and
focus on truly valid and proven effective treatment. The author tries to find the truth,
debunk myths, and explain the correct efficacious treatment. Dr. S. Silber is very
open in personally explaining the solid reasons for his approach.
There are certainly many treatments for male infertility which are not proven to
be helpful. This book opens the avenue to the correct approach, exposing dubious
and irrelevant treatments.
One example of a completely irrelevant approach is the operative intervention to
cure varicocele. Millions of males have undergone this surgery without any positive
effect. There is no good evidence in favor of this operation. We can hope that this
book will inform the reader and eliminate this useless and meddlesome operation.
Even when we cannot treat the male, we can treat his gametes. The discovery of
in vitro fertilization with ICSI has been a key milestone in the treatment of female
and also male infertility. Furthermore, the advent of vitrification for freezing eggs
and embryos and individual single sperm, the genetic control of spermatogenesis,
and even how to make spermatozoa from skin cells will inspire all of us.
Dr. Silber explains very clearly how intracytoplasmic sperm injection (ICSI) has
changed the world of male infertility treatment. Only one sperm is needed to obtain
a healthy pregnancy. The most inspiring thinking of the book is related to the fact
that even males with extreme oligospermia do have the same chance to initiate a
v
vi Foreword
viable pregnancy as the male with completely normal sperm. In the past, males with
azoospermia were hopelessly sterile. But after testicular sperm extraction (TESE)
the quality of sperm is sufficient to obtain normal pregnancies with ICSI.
This book analyzes the basic science and treatment of male factor infertility with
Dr. Silber’s characteristic honesty and clear thinking. It describes finally what works
and what doesn’t work. It will inspire most readers who wish to understand male
infertility better.
Brussels, Belgium Paul Devroey

2018
Historical Preface
I hope this book will give you a rational and up-to-date explanation of both the sci-
ence and clinical treatment of male infertility. Of course this includes endocrinol-
ogy, and genetics. But modern male infertility treatment began historically with
microsurgery. My 47-year history of developing a rational approach to male infertil-
ity began in 1970 when I was just a urology resident at the University of Michigan
in Ann Arbor, not at all interested in infertility. That was before the incredible
advances in andrology. But our modern understanding and treatment of the male
developed originally with the popularization of microsurgery. So it would be useful
to start with a historical introduction to male reproductive microsurgery.
My initial goal was just to understand compensatory renal hypertrophy, i.e., why
when you remove one kidney, the other kidney compensates, and renal function of the
remaining kidney is almost doubled. To answer this question, I decided in 1969 to
transplant extra kidneys into animals, to see if the reverse would occur, i.e., would the
kidneys “hypotrophy”? I did not want the experiment to be hampered by allogenic
rejection, and the largest animal inbred enough to avoid rejection was the rat. So I
developed in my earliest papers in the early 1970s a whole field of microvascular
surgery in urology [1, 2]. With the help and instruction of a brilliant janitor at the
University of Michigan animal lab, Jimmy Crudop, I transplanted extra kidneys from
one Lewis rat into another Lewis rat using donor renal artery and vein anastomosis to
the recipient aorta and vena cava. The rat renal artery was only 0.3 mm in diameter
and the aorta was only 1.0 mm in diameter. Such microscopic surgery at the time
seemed almost unbelievable. I thus unintentionally became a pioneer in microsurgery,
purely in order to study renal physiology, not infertility (Figs. 1, 2, 3, 4, 5, and 6). It
was subsequently only as a result of this effort that the modern field of male infertility
treatment evolved. For historic reasons, therefore, it is appropriate to give a short his-
tory of urologic microsurgery.
We found that the kidneys did not reduce in size, but rather these animals had two
times the renal function with four kidneys than controls with two kidneys [3–6]. On
the other hand, when we removed one kidney from a rat, so that the other kidney
doubled in size, and we transplanted two of those hypertrophied kidneys back into
one animal, they reduced back to their original size. Renal function reverted quickly
vii
Fig. 1 Microvascular surgery in rat: end-to-side microvascular anastomosis of renal vein to vena
cava (1 mm diameter)
Fig. 2 Microvascular end-to-side anastomosis in rat renal vein to vena cava (1 mm)
Fig. 3 Intravenous
pyelogram of rat showing
three functioning kidneys
Fig. 4 Ureteral bladder anastomosis in rat

x Historical Preface
Fig. 5 Using the timer end-to-end anastomosis of rat renal artery and vein and ureter, we could do
experiments that left the donor alive
Fig. 6 Completed end-to-end anastomosis of rat renal artery (1/3 mm), renal vein (1 1/2 m), and
ureter (1/3 mm)
Historical Preface xi
from twice normal to normal. This research led to many advances in renal transplan-
tation in the 1970s: the prevention of renal failure after kidney transplantation by
salt loading the rats before inducing prolonged ischemia times, prolonged hydration
and osmotic loading prior to surgery, the limits of warm and cold ischemic time a
kidney (or ovary or testis) could tolerate before permanent loss of function, and
preventing allograft rejection using prior properly timed injection of donor antigens
[7–9]. Thus when I left Ann Arbor, Michigan, and Melbourne, Australia (1969–
1975), I was known as a kidney transplanter and microvascular surgeon. But I had
no idea I would ever be an infertility doctor.
While in Melbourne, I worked with Bob Fowler and Douglas Stephens, who
were very unhappy with their popular “Fowler-Stephens” operation for intra-
abdominal cryptorchid testis, because of the high frequency of ischemic testis atro-
phy. So we developed the microvascular testis autotransplant procedure, using the
same microvascular technique on human spermatic artery and vein that Jimmy
Crudop and I had developed for renal artery and vein in rats (Figs. 7, 8, 9, and 10)
Fig. 7 Anatomy in human for microvascular testis autotransplant for high cryptorchid abdominal
testis
xii Historical Preface
Fig. 8 Photograph of
typical intra-abdominal
cryptorchid testis in a child
that could not be brought
down into the scrotum
without dividing the
spermatic vessels
Fig. 9 Division of spermatic (1/2 mm) vessels to bring down high cryptorchid testis
Historical Preface xiii
Fig. 10 Completed re-anastomosis of spermatic vessels (1/3 mm) to bring down intra-abdominal
testes
[10]. We divided the spermatic artery and vein of these young boys, which other-
wise would keep the testis tethered up high, and we re-anastomosed them to the
inferior epigastric artery and vein. This allowed the intra-abdominal testis otherwise
high up near the kidney, to be safely brought down to the scrotum (Figs. 11, 12, 13,
and 14). Fowler and Stephens adopted this procedure and indeed gave me credit for
it. But many urologists who were not microvascular surgeons continued to use only
the more destructive Fowler-Stephens operation (which Bob Fowler and Douglas
Stephens abhorred).
Before leaving Melbourne in 1975, I worked with the famed plastic surgeon Ian
Taylor to perform one of the first human free microvascular skin grafts. I had taught
Ian Taylor how to do microvascular anastomosis in rats in Peter Morris’s lab in
xiv Historical Preface
Fig. 11 This micro-

arteriogram demonstrates
the arterial and venous
vasculature of the human
testis. To anastomose such
a tiny spermatic artery to
the larger inferior
epigastric needed a
modified end-to-side
approach
Fig. 12 A picture of the

completed anastomosis in
the first human testis
transplant of the spermatic
artery spatulated to the
inferior epigastric artery.
Our hearts pounded when
we removed the clamps,
and good pulsatile blood
flow was observed
Historical Preface xv
Fig. 13 The first large free

groin skin flap
microvascular transfer by
the author and Ian Taylor
in Melbourne, Australia
Fig. 14 The author and Dr. Ian Taylor in 1975 performing world’s first free microvascularized
groin and bone flap, using techniques honed in the rat lab
xvi Historical Preface
Fig. 15 The original

two-layer microsurgical
re-anastomosis of vas
(vasovasostomy)
Melbourne, and Ian had worked out the anatomy of the skin of the groin. So together
we performed the world’s first free huge vascularized skin flap and bone graft oper-
ations, which revolutionized reconstructive plastic surgery.
In 1978, using these same microsurgery techniques we performed the first human
testis transplant, from an identical twin with two normal testes to his brother who
was born with anorchia [11]. These testis transplants worked perfectly, and resulted
in five healthy babies from spontaneous pregnancy. This microsurgery was praised
at the AUA (American Urological Association) meeting that year by the great
Dr. Willard Goodwin of UCLA urology fame. But I never dreamed of the impact
which these techniques would have on vasectomy reversal. In fact I considered that
to be just an insignificant fun thing to do, but not very important. I honestly thought
that no one who had a vasectomy would ever want it reversed (Fig. 15). So the origi-
nal papers I wrote on microsurgery to reverse vasectomy seemed to me to be trivial.
But I guess they weren’t.
After presentation of a live telecast on closed circuit TV at the American College
of Surgeons meeting in San Francisco in October of 1975, with a team of urology
discussants it became the main story on the front page of The New York Times. This
was in 1975, 3 years before IVF. It was shocking to the world that we could get such
high pregnancy rates in otherwise azoospermic men by simply doing a better micro-
surgical anastomosis [12]. It had been thought erroneously before this that the con-
sistent failure of vasectomy reversal was due to sperm antibodies, which has
subsequently been disproven [13–15]. The cause of the consistent failure of vasec-
tomy reversal was not auto-immunity, but rather just mechanical failure to re-
establish accurate continuity.
There was however great controversy in the late 1970s. Some called vasectomy
reversal “immoral.” They would actually argue at urology meetings, “if a man has
had a vasectomy, it is unethical to reverse it.” Others said “you don’t need a micro-
scope,” and some even apocryphally claimed they already were doing this. Others
thought we were lying, the same as the British Medical Society thought of Steptoe
and Edward’s IVF in 1978. Many questioned if we actually performed a two-layer
Historical Preface xvii
anastomosis of this tiny structure. We used 10-0 nylon interrupted stitches for the
inner mucosa, and 9-0 for the outer muscle. At this time, 45 years ago, urologists
had no idea what a 10-0 nylon suture was. Some who resisted using a microscope
claimed that two layers were not necessary. But eventually everyone finally accepted
that microsurgical two-layer anastomosis was the proper procedure for vasovasos-
tomy. Nonetheless, I suffered extreme criticism because of fear of a future that
many could not accept. Only Bruce Stewart of the Cleveland Clinic supported me in
the beginning. But eventually most urologists in the world adopted this procedure.
However, we noted in my 1977 papers that if there was no sperm in the vas fluid
at the time of vasovasostomy, the operation always failed, despite a perfect anasto-
mosis. Furthermore the testis biopsy, despite no sperm in the vas fluid, always
showed normal spermatogenesis. Also if there was a sperm granuloma at the vasec-
tomy site, there was always the sperm in the vas fluid, and virtually all vasovasosto-
mies then were successful [16–18]. In fact we recommended “open-ended”
vasectomy to ensure the formation of sperm granuloma as early as 1978. We were
promptly ridiculed for this suggestion, but we were, and still are, correct [19].
Because of this observation, we explored the epididymis in men with no sperm
in the vas fluid—remember, spermatogenesis is always normal in these men
(Fig. 16)—and found pressure-induced secondary epididymal extravasation and
blowouts, and thus, secondary epididymal obstruction was found in all of these
cases with no sperm in the vas fluid [20]. Until then, it was not generally appreciated
that there was always increased pressure buildup after vasectomy. This resulted in
Fig. 16 Transecting the epididymis proximally in men who had no sperm in the vas fluid always
revealed epididymal secondary obstruction (and normal spermatogenesis)
xviii Historical Preface
extravasculation in the epididymis and secondary epididymal blockage. Furthermore

if the vasectomy were formed loosely, so that there was sperm leakage at the vasec-
tomy site, there was less pressure buildup, and there was no epididymal obstruction.
So in those cases microsurgical vasovasostomy was almost always successful. At
that time we found that the longer the duration of time since vasectomy the greater
was the incidence of epididymal blowouts, due to a longer interval of increased
pressure. Poor results were not caused by damage to the testis owing to a long dura-
tion of obstruction, although to this day patients are erroneously being told this. We
actually wrote the original papers that showed success rates for vasovasostomy were
better if the vasectomy was less than 10 years before the reversal. However this was
not due to testicular damage.
So for cases where there was no sperm in the fluid we invented the “specific
tubule” vasoepididymostomy [21]. The technique of vasoepididymostomy for
obstructive azoospermia previously was to make a gross fistula between the vas
deferens, and an opening in the epididymal tunica, with terribly low success
(Fig. 17). But when we discovered that failure of vasectomy reversal was due to
Fig. 17 The old method of vasoepididymostomy before the author’s single specific tubule method
in 1978
Historical Preface xix
Fig. 18 The author’s end to end specific tubule vasoepididymostomy
secondary epididymal obstruction, we realized that we needed to achieve better

results with vasoepididymostomy. So in 1978 we developed a microsurgical proce-
dure for anastomosing the inner mucosa of the vas deferens to the very delicate
specific tubule of the epididymis proximal to the site of obstruction [21]. The results
were astoundingly as good as with vasovasostomy when there was sperm in the vas
fluid (Fig. 18). This again was at first greeted with disbelief and initially disdain.
Most urologists still shy away from this approach even today, but our success rate
argues in favor of it [22]. Originally we transected the epididymis serially and proxi-
mally until we were beyond the obstruction, as evidenced by the finding of good
quality sperm (Fig. 17). This was an end-to-end anastomosis. Eventually we
switched to an end-to-side anastomosis but retained our original concept of anasto-
xx Historical Preface
Fig. 19 (a–d) Modified end-to-side vas to epididymostomy
mosis to the specific epididymal tubule, disbanding the previous concept of just
creating a fistula (Fig. 19a–d).
However there were cases of obstructive azoospermia where there was no vas
(CBVAD, or congenital absence of vas), for which we developed the MESA proce-
dure first with conventional IVF in 1986, and then with ICSI in 1992 (Fig. 20).
Again, remarkably, pregnancy and live baby rates were no different from couples
with normal sperm counts in their ejaculate [23, 24–31]. Then even more remark-
ably in Brussels, when there was no epididymis at all, we reported in 1993 that
testicular nonmotile sperm with ICSI resulted in normal pregnancy and live baby
rates [25, 32]. We coined that procedure TESE (testicular sperm extraction). We still
have the original napkin from the surgeon’s lounge in Brussels where Paul Devroey
wrote this down when we coined the eponym “TESE” [24–27, 33]. We also changed
the basic science concept of epididymal function. It had been thought that the most
motile sperm would be the most distal that had transversed through most of the
epididymis, but we discovered that in obstructive azoospermia, the opposite was
true, and only found good motility in the most proximal sperm. Then in 1994, we
found that even with azoospermic men who had no obstruction (and seemingly no
spermatogenesis at all), there were often (over 50%) a very tiny number of rare
sperm in the testis, which were adequate for successful ICSI with normal pregnancy
[25, 34]. This was based on our original papers of quantitative histologic exam of
testis biopsy specimens in the 1970s [35].
We then used these early micro-TESE patients who had nonobstructive azo-
ospermia to map and sequence the Y chromosome, beginning in 1992 at the Page
Historical Preface xxi
Fig. 20 For MESA, where there was no vas, we found that the most viable motile sperm were
proximal, nondistal as most had previously thought
lab at MIT, and thereby discovered genes on the Y that control spermatogenesis and
are deleted in infertile men [36]. This was the now famous DAZ gene (we in fact
coined the term DAZ). From there the Page lab discovered autosomal DAZL on
chromosome 3. As it now turns out DAZL is the major ancestral universal gene that
“licenses” early embryonic stem cells to become germ cells, either sperm or in fact
eggs. DAZ, or DAZL, turns out to be the most common key to spermatogenesis and
oogenesis in most animals going very far back in the phylogenetic tree.
With our development of microsurgical TESE, we discovered the simplest way
to avoid adhesions, which obviously applies to tubal microsurgery in the female as
well. Whenever we had to re-operate on these men with nonobstructive azoosper-
mia, to retrieve more sperm, there were never any adhesions in the tunica albuginea
space. It was as though there had never been any previous surgery in his scrotum.
We realized that this was an affirmation within the scrotum of the principles of mini-
mal tissue trauma, perfect hemostasis, and pulsatile irrigation with heparinized
saline promulgated by Gomel and Winston in tubal microsurgery. There was no
commercial adhesion prevention product that could compare with just keeping the
tissue constantly wet with heparinized saline, and using micro-bipolar forces for
hemostasis with no tissue damage.
As important as was prevention of adhesions was how to avoid testis tissue dam-
age with microsurgery, despite total exploration of the testis to find those rare sperm
in an azoospermic male. We avoided intra-testicular swelling and subsequent testis
atrophy by stopping all bleeding with micro-bipolar forceps and closing the tunica
albuginea (which has no elasticity) with 9-0 nylon interrupted sutures, rather than
the prevailing running stitch with 4-0 vicryl. This prevents a purse string reduction
xxii Historical Preface
in testis volume and subsequent pressure atrophy. Furthermore, we studied the loca-
tion of spermatogenic stem cells (SSCs) and realized that the surgeon does not have
to “dig into” the testis to find the rare sperm. One can stay on the periphery of the
seminiferous tubules and nonetheless sample every anatomic lobule. If there is a
SSC anywhere within the testis, you will find sperm at the periphery of the tubule
where it loops around. Thus you avoid any internal testis damage (as can occur with
a deeply invasive “microdissection” technique).
Varicocelectomy has been a very popular operation for infertile men since 1952.
I am no longer an advocate of that procedure (even though for many urologists it is
still very popular). However, I did make it a much safer procedure in 1979 by being
the first to suggest a microsurgical approach, thus sparing damage to the tiny sper-
matic artery [37]. Prior to that, there was a 5% incidence of painful hydrocele, and
often testicular atrophy or a reduction (rather than increase) in spermatogenesis
because of spermatic artery damage. In addition, recurrence of the varicocele,
because of failure to ligate every spermatic vein, was common. Although before
1979 no one used a microsurgical approach to varicocelectomy, now everyone does.
However, the vast majority of infertility doctors, who are not urologists, do not
believe in varicocelectomy. They feel that when men undergo this procedure, wait-
ing for the sperm count to improve, the wife’s eggs are simply getting older. My
views on this will be explained and documented in detail in this book.
Most recently, we have turned our attention to culturing and freezing spermatogo-
nial stem cells (SSCs) in order to transplant them back after sterilizing chemotherapy
in prepubertal boys with cancer. We have analyzed with single cell analysis of gene
transcription revealing the genomics of spermatogenesis, and identified the hereto-
fore elusive human SSCs. We can easily freeze a TESE specimen from a prepubertal
boy today, and then when he is an adult, culture and amplify the number of SSCs,
and then transplant them later into his azoospermic testis. Such spectacular progress
in andrology was made possible focusing on microsurgery, genetics, and cell culture.
In addition, by understanding the culturing (and freezing) of SSCs, and determining
the entire transcriptome of spermatogenesis, there will be great progress in the future
for male infertility treatment. For example, we can culture and amplify the SSCs
from a TESE specimen, then inject them back into the rete testis of azoospermic
men, and thereby increase their spermatogenesis. Furthermore, in mice it is possible
to generate sperm (and eggs) from stem cells derived from a skin biopsy.
It is important for andrologists to understand not only male fertility but also
female. For example, we performed the first successful frozen ovary transplant in
2004 in the United States [38]. We have a series of many healthy babies from these
procedures in women who had been menopausal for more than 5 years, either from
POF or from cancer treatments [39–41]. As a result of scientific study of this
remarkable series of human ovary transplants, we have deciphered the duration of
time in the human between primordial follicle recruitment and ovulation, as well as
the heretofore mysterious control of that oocyte recruitment. Furthermore, by study-
ing the development of human oocytes from the skin cells of our identical twins
discordant for premature ovarian failure, we are currently determining at what
embryonic stage PGC (primordial germ cell) specification occurs in the human
Historical Preface xxiii
embryo. Furthermore, we are on the brink of being able to make SSCs (thus normal
sperm) from IPS cells derived from skin. This will be explained in detail in the last
section of this book. In the future we will actually be able to make sperm in azo-
ospermic men from skin.
So it has been a long, almost half-century journey from my first microsurgical
experiments in rats to remarkable advances in the understanding and treatment of
human infertility, both in the male and the female. In fact our results with vasectomy
reversal, tubal reversal, and vasoepididymostomy are still stunning, despite the
great ease now of microsurgery for MESA, TESE, and IVF which evolved from
those original studies in the early 1970s in rats [22, 42–44]. The new advances for
male infertility amazingly now are ICSI, freezing and transplantation of SSCs, as
well as deciphering the entire genetic transcriptome of spermatogenesis, and mak-
ing sperm from a man’s skin via IPS cell transformation. The objective of this book
is to give you the fundamentals necessary for rationally and successfully dealing
with male infertility in a leading edge manner.
St. Louis, MO Sherman Silber
References
1. Silber SJ, Crudop J (1973) Kidney transplantation in inbred rats. Am J Surg 125:551–553
2. Silber SJ, Crudup J (1974) The three-kidney rat model. Invest Urol 11:466–470
3. Silber S, Malvin RL (1974) Compensatory and obligatory renal growth in rats. Am J Physiol
226:114–117
4. Silber SJ (1974) Renal transplantation between adults and children. Differences in renal
growth. JAMA 228:1143–1145
5. Silber SJ (1974) Extra renal function in patients with duplication anomaly: obligatory and
compensatory renal growth. J Urol 112:423–424
6. Silber SJ (1976) Growth of baby kidneys transplanted into adults. Arch Surg 111:75–77
7. Silber SJ (1974) The prevention of acute tubular necrosis in renal transplantation by chronic
salt loading of the recipient. Aust N Z J Surg 44:410–412
8. Silber SJ (1975) Transplantation of rat kidneys with acute tubular necrosis into salt-loaded and
normal recipients. Surgery 77:487–491
9. Silber SJ, Miller JF, Morris PJ (1976) Graft-versus-host reactivity and renal allograft survival
in rats given allogeneic spleen cells or spleen allografts. Transplantation 22:160–166
10. Silber SJ, Kelly J (1976) Successful autotransplantation of an intra-abdominal testis to the
scrotum by microvascular technique. J Urol 115:452–454
11. Silber SJ (1978) Transplantation of a human testis for anorchia. Fertil Steril 30:181–187
12. Brody EJ. (1975, October 8). New York Times. p. 1. Retrieved from http://www.nytimes.
com/1975/10/08/archives/microsurgery-successful-in-vasectomy-reversals-vasectomy-test.
html?mcubz=0
13. Silber SJ (1977) Microscopic vasectomy reversal. Fertil Steril 28:1191–1202
14. Silber SJ (1977) Perfect anatomical reconstruction of vas deferens with a new microscopic
surgical technique. Fertil Steril 28:72–77
15. Silber SJ, Galle J, Friend D (1977) Microscopic vasovasostomy and spermatogenesis. J Urol
117:299–302
16. Silber SJ (1977) Sperm granuloma and reversibility of vasectomy. Lancet 2:588–589
17. Silber SJ (1978) Vasectomy and vasectomy reversal. Fertil Steril 29:125–140
18. Silber SJ (1978) Vasectomy and its microsurgical reversal. Urol Clin North Am 5:573–584
xxiv Historical Preface
19. Shapiro EI, Silber SJ (1979) Open-ended vasectomy, sperm granuloma, and postvasectomy
orchialgia. Fertil Steril 32:546–550
20. Silber SJ (1979) Epididymal extravasation following vasectomy as a cause for failure of vasec-
tomy reversal. Fertil Steril 31:309–315
21. Silber SJ (1978) Microscopic vasoepididymostomy: specific microanastomosis to the epididy-
mal tubule. Fertil Steril 30:565–571
22. Silber SJ, Grotjan HE (2004) Microscopic vasectomy reversal 30 years later: a summary of
4010 cases by the same surgeon. J Androl 25:845–859
23. Devroey P, Liu J, Nagy Z, Tournaye H, Silber SJ, Van Steirteghem AC (1994) Normal fertiliza-
tion of human oocytes after testicular sperm extraction and intracytoplasmic sperm injection.
Fertil Steril 62:639–641
24. Silber SJ, Van Steirteghem AC, Devroey P (1995) Sertoli cell only revisited. Hum Reprod
10:1031–1032
25. Silber SJ, Van Steirteghem AC, Liu J, Nagy Z, Tournaye H, Devroey P (1995) High fertiliza-
tion and pregnancy rate after intracytoplasmic sperm injection with spermatozoa obtained from
testicle biopsy. Hum Reprod 10:148–152
26. Silber SJ, Devroey P, Tournaye H, Van Steirteghem AC (1995) Fertilizing capacity of epi-
didymal and testicular sperm using intracytoplasmic sperm injection (ICSI). Reprod Fertil Dev
7:281–292; discussion 92–3
27. Silber SJ, Nagy Z, Liu J, et al (1995) The use of epididymal and testicular spermatozoa for
intracytoplasmic sperm injection: the genetic implications for male infertility. Hum Reprod
10:2031–2043
28. Silber SJ, Nagy ZP, Liu J, Godoy H, Devroey P, Van Steirteghem AC (1994) Conventional in-
vitro fertilization versus intracytoplasmic sperm injection for patients requiring microsurgical
sperm aspiration. Hum Reprod 9:1705–1709
29. Silber SJ, Ord T, Balmaceda J, Patrizio P, Asch RH (1990) Congenital absence of the vas def-
erens. The fertilizing capacity of human epididymal sperm. N Engl J Med 323:1788–1792
30. Asch RH, Patrizio P, Silber SJ (1992) Ultrastructure of human sperm in men with congenital
absence of the vas deferens: clinical implications. Fertil Steril 58:190–193
31. Silber S, Ord T, Borrero C, Balmaceda J, Asch R (1987) New treatment for infertility due to
congenital absence of vas deferens. Lancet 2:850–851
32. Devroey P, Liu J, Nagy Z, et al. (1995) Pregnancies after testicular sperm extraction and intra-
cytoplasmic sperm injection in non-obstructive azoospermia. Hum Reprod 10:1457–1460
33. Silber SJ (1996) Sertoli cell only syndrome. Hum Reprod 11:229
34. Silber SJ, van Steirteghem A, Nagy Z, Liu J, Tournaye H, Devroey P (1996) Normal pregnan-
cies resulting from testicular sperm extraction and intracytoplasmic sperm injection for azo-
ospermia due to maturation arrest. Fertil Steril 66:110–117
35. Silber SJ, Rodriguez-Rigau LJ (1980) Pregnancy after testicular transplant: importance of
treating the couple. Fertil Steril 33:454–455
36. Silber SJ (2011) The Y chromosome in the era of intracytoplasmic sperm injection: a personal
review. Fertil Steril 95:2439–2448 e1–e5
37. Silber SJ (1979) Microsurgical aspects of varicocele. Fertil Steril 31:230–232
38. Silber SJ, Lenahan KM, Levine DJ, et al. (2005) Ovarian transplantation between monozygotic
twins discordant for premature ovarian failure. N Engl J Med 353:58–63
39. Silber S (2015) Unifying theory of adult resting follicle recruitment and fetal oocyte arrest.
Reprod Biomed Online 31:472–475
40. Silber S, Pineda J, Lenahan K, DeRosa M, Melnick J (2015) Fresh and cryopreserved ovary
transplantation and resting follicle recruitment. Reprod Biomed Online 30:643–650
41. Silber S (2016) Ovarian tissue cryopreservation and transplantation: scientific implications. J
Assist Reprod Genet 33:1595–1603
42. Silber SJ (ed) (1980) Microsurgery. Williams & Wilkins, Baltimore, MD, p 492 1979
43. Silber SJ (1985) Reproductive infertility microsurgery in the male and female. Williams and
Wilkins, Baltimore, MD, 1984
44. Silber, S.J. (in press). Fundamentals of Male Infertility. Springer, 2017
Acknowledgments
Manuscript Preparation:
Sierra Goldsmith
Infertility Center of St. Louis
St. Louis, Missouri, USA
Research Collaborations:
Adjunct Professor OB-GYN Kyushu University Medical School
University of Amsterdam Fukuoka, Japan
Amsterdam, The Netherlands
University of California Los Angeles
Adjunct Professor OB-GYN Molecular Biology Institute
Sun Yat-sen University of Medical Los Angeles, California, USA
Sciences
University of Texas Southwestern
Guangdong, China
Medical Center
Kato Ladies Clinic Dallas, Texas, USA
Tokyo, Japan
Massachusetts Institute of
Technology
Massachusetts, USA
xxv
Contents
Part I Basic Science of the Testis

1 Testis Development, Embryology, and Anatomy�� 3
References�� 11
2 Descent of the Fetal Testis from the Abdomen to the Scrotum�� 13
References�� 17
3 Adult Testis Anatomy�� 19
References�� 21
4 Structure of the Seminiferous Tubules�� 23
5 Blood Supply to the Testis �� 25
References�� 27
6 Histology of the Testis and Spermatogenesis�� 29
References�� 37
7 Hormonal Regulation of Spermatogenesis�� 39
References�� 40
8 Meiosis�� 43
Part II Evaluation and Treatment of Male Infertility

9 Evaluation of Male Infertility �� 47
9.1 How to Interpret the Semen Analysis �� 48
9.2 Male Infertility and the Female Factor �� 51
9.3 Sperm Morphology �� 52
9.4 Zona Binding, Sperm Penetration, and In Vitro Fertilization�� 54
9.5 Other Various Tests of Sperm Function�� 55
References�� 56
xxvii
xxviii Contents
10 Treatment of Male Infertility�� 59

10.1 Critique of Classic Andrologic Treatments�� 59
10.2 Intracytoplasmic Sperm Injection (ICSI) for Male Infertility�� 63
10.3 How Is ICSI Done and IUI (Intrauterine Insemination) �� 63
10.3.1 Details of the ICSI Technique �� 63
10.3.2 Pitfalls of Sperm Injection (ICSI) �� 65
10.3.3 Preparing the Eggs and the Sperm for ICSI�� 70
References�� 74
11 Azoospermia �� 77
11.1 Evaluation of the Azoospermic Man�� 78
11.2 Diagnostic Testicle Biopsy�� 79
11.3 Microsurgical Vasovasostomy�� 83
11.4 Technique of Vasovasostomy�� 85
11.5 Results of Vasovasostomy�� 86
11.6 Microsurgical Vasoepididymostomy�� 88
11.7 Congenital Absence of Vas �� 95
11.8 MESA: Microsurgical Sperm Aspiration with ICSI �� 96
11.9 Testicular Sperm Extraction (TESE) for Nonobstructive
Azoospermia (NOA) �� 102
11.10 The Round Spermatid Controversy�� 110
11.11 Micro-TESE: What Is the Best Method?�� 114
11.12 Best Method for Micro-TESE�� 115
References�� 123
12 Karyotyping of Infertile Males and Their ICSI Offspring�� 127
12.1 Karyotyping�� 127
12.2 Klinefelter’s Syndrome �� 129
13 Donor Sperm�� 131
13.1 Is It My Baby?�� 131
13.2 How to Select the Donor�� 133
13.3 Frozen Sperm and Sperm Banks�� 136
13.4 Insemination with Donor Sperm or ICSI with Donor Sperm �� 137
14 Cryopreservation of Sperm�� 139
14.1 Introduction�� 139
14.2 Methodology Details�� 140
14.3 Single Sperm Cryopreservation�� 140
15 Varicocele�� 143
15.1 Lack of Effect of Varicocele on Pregnancy Rate
Following Vasovasostomy�� 145
15.2 Evidence-Based Practice of Medicine�� 145
Contents xxix
15.3 Varicocelectomy and Sperm Count�� 146

15.4 Does Varicocele Cause a Progressive Decline in Fertility?�� 147
16 Kallman’s Syndrome and Hypopituitarism�� 151
Part III New Frontiers

17 The Genetic Control of Male Infertility and Understanding the Y
Chromosome�� 157
17.1 The Y Chromosome and ICSI�� 158
17.2 AZFa �� 159
17.3 AZFb �� 161
17.4 AZFc �� 162
17.5 The DAZ Gene Family�� 163
17.6 Mechanism of De Novo Y Chromosome Deletions�� 164
17.7 Evolution of the Human Y Chromosome�� 165
17.8 The Y Chromosome and Spermatogenesis in Humans
and in Apes and “Sperm Competition”�� 167
17.9 Other Male Infertility Genes Not Discernible on the
Y Chromosome �� 168
17.10 Transmission of Y Deletions to ICSI Offspring �� 169
18 Spermatogenic Stem Cell Cryopreservation and Transplantation�� 179
18.1 Brinster’s Original Studies�� 179
18.2 Clinical Applications for Cancer Patients and Also to
Improve Sperm Count�� 180
19 Making Sperm from Skin Cells�� 187
20 Identification of Spermatogonial Stem Cells and Genetic Control
of All Stages of Spermatogenesis�� 193
Part I
Basic Science of the Testis
Another random document with
no related content on Scribd:
COURSE AND DURATION.—The onset of the disease is sudden. The
symptoms in the first two stages may last only for a few minutes and
pass off, or the disease may pass through all the stages and
terminate in gangrene. It is usual for the first stage of ischæmia to
last several days, varying in severity; for the second stage to last
several days; and for the stage of gangrene to occupy about three
weeks. The shortest duration of a single attack has been ten days,
the longest five months. If the gangrene begins simultaneously in all
the fingers, the duration will be shorter than if it proceeds to one after
another. In one-third of the cases a recurrence of the disease within
a year of the first attack has been observed, and it is probable that
the proportion would have been larger had all the patients been kept
under observation. In some cases three and four attacks have
succeeded each other with some rapidity, some of the attacks being
much less severe and shorter than others. In some cases the
condition of gangrene has developed only in one out of three
attacks. When the condition is one of local erythema the duration
may be indefinite, the state becoming chronic and lasting for several
years.
NATURE.—The nature of the disease is a matter of deduction from the

study of the symptoms, no autopsies having as yet been made. As
already stated, the symptoms are explained on the theory of a vaso-
constrictor irritation in the stages of ischæmia and cyanosis—of a
vaso-dilator irritation in the stage of erythema. Whether this irritation
is the direct result of abnormal processes going on in the vaso-motor
centres in the spinal cord, or is the reflex result of irritation arising
elsewhere, is undetermined. Raynaud held that it must be of central
origin, since in his cases galvanization of the spinal cord modified
the arterial spasm. The latter observation has not been confirmed by
other observers. Weiss believes that the condition may occur in
response to irritation arising in the skin, in the viscera, or in the brain,
and thus prefers the theory of reflex origin. This theory is adopted by
several observers, who find a source for such irritation in the female
genital organs in their cases.
ETIOLOGY.—The disease occurs in adult life, only two cases having
been observed in persons fifty years old. It is most frequent between
the ages of fifteen and thirty, although children and adults beyond
the age of thirty are about equally liable. Females are more liable to
it than males, four-fifths of the recorded cases having been in
women. It occurs more frequently in the winter months, exposure to
cold being a common exciting cause. Other exciting causes are
nervous exhaustion, especially occurring in those who are
predisposed to nervous diseases by heredity; general weakness
from anæmia, malnutrition, or the occurrence of acute fever or
exhausting disease; and mental agitation, a fright having preceded
the attack in several cases. In women menstrual disorders and
uterine disease have been considered as etiological factors.
Occupation has something to do with its occurrence, since
washerwomen, waitresses, and chambermaids are the class most
often affected. In many cases, however, no cause of local irritation
can be found.
DIAGNOSIS.—The diagnosis rests upon the development of vaso-

motor symptoms in the extremities, situated symmetrically, going on
to gangrene, in a person not afflicted with cardiac disease or with
endarteritis of any kind, and not having been exposed to frost-bite or
ergot-poisoning. The age of the patient, the symmetrical position of
the symptoms, the persistence of the pulse in the main arteries, and
the limitation of the gangrene to the tips of the extremities distinguish
it readily from senile gangrene. The history of the case, the absence
of itching, and the presence of pain during the arterial spasm which
passes off when the spasm ceases, serve to separate it clearly from
chilblains. Congenital cyanosis is produced by cardiac anomalies,
and the entire body is affected. Ergot-poisoning can be ascertained
by the history.
PROGNOSIS.—Life is not endangered by this disease, no fatal cases

having been recorded. Recovery from an attack is certain, but the
duration cannot be stated, as it will depend in any case on the
character, the extent, and the severity of the symptoms. The
possibility of a recurrence of the attack should be stated to the
patient.
TREATMENT.—The methods of treatment have varied, and none are

wholly satisfactory. If the causes can be met—e.g. anæmia, nervous
exhaustion—they should be treated. If not, the disease itself may be
attacked by means of electricity. Or the symptoms may be treated as
they demand it. Electricity has been used by almost all observers.
The faradic current produces an aggravation of all the symptoms
except in the stage of erythema, and has been discarded. The
galvanic current may be employed in several ways. Two methods
are in use. In the first the positive pole is applied over the cervical
region, and the negative pole over the lumbar region, a descending
current being thus sent through the spinal cord. The current should
be of moderate strength, not above twenty-five milliamperes, few
patients being able to endure the strength implied in Raynaud's
statement that he used sixty-four cells of a Daniel battery. The
duration of the application should be ten minutes, and the electricity
may be applied once daily. In the second method the anode is
applied over the brachial or lumbar plexus, as the case may be, and
the cathode passed over the affected extremity, the current being
constant and care being taken not to break it suddenly. The strength,
duration, and frequency should be the same as in the first method.
From these two methods, separately or combined, Raynaud claimed
to have seen favorable results. His assertions have not been
confirmed by other observers who have followed his directions
closely, and hence considerable doubt at present prevails as to the
efficacy of the electric current. The so-called electrical application to
the cervical sympathetic is certainly useless. In the stage of
erythema a very weak faradic current applied to the hands in a bath
may be of service.
Many observers have found that the progress of the case to recovery
was quite rapid if the limb were put at rest in an elevated position,
were kept warm by cotton batting or similar bandaging, and were
kept clean with antiseptic lotions when the stage of gangrene set in.
Massage is to be used in all cases, the limbs or affected parts being
gently rubbed with the dry hand or with aromatic liniments or oils. All
local injury, however, and especially counter-irritation, are to be
carefully avoided. General tonic treatment, especially iron and cod-
liver oil, is to be used in all cases.
The pain occurring in the early stages is often so severe as to

require the use of opium or other narcotics. And when the nervous
symptoms are especially aggravated, and irritability and insomnia
give the patient discomfort, bromide and chloral may be employed.
Diseases of the Cervical Sympathetic.
ETIOLOGY.—Diseases of the cervical sympathetic ganglia or cord may

be of two kinds—either irritative or destructive.61 They are produced
by pressure upon the cervical ganglia or upon the sympathetic cord
between these ganglia, by tumors, especially aneurisms, and
enlarged glands; by abscesses; and by cicatrices of old wounds in
the neck. They are also due to extension of inflammation from a
thickened pleura in phthisis and chronic pleuritis of the apex. They
may be caused by injuries, such as stab-wounds, gunshot wounds,
etc. Any disease which produces marked irritation of peripheral
branches of the sympathetic in the neck, or of the cerebro-spinal
cervical nerves, may cause reflex phenomena resembling the
symptoms of actual disease. From such phenomena it is not
justifiable to conclude that the sympathetic cord and ganglia are the
seat of lesions, and the only cases which will be considered here are
those in which actual disease was proven to be present by an
autopsy.
61 Ogle, Medico-Chirurgical Transactions, xli. 397-440, 1858, 27 cases; Poiteau, “Le
Nerf sympathetique,” Thèse de Paris, 1869, 19 cases; Eulenburg and Guttmann, Die
Pathologie der Sympathicus, 1873; Nicati, Le Paralysie du Nerf sympathique-
cervicale, 1873, 25 cases; Seeligmüller, Inaug. Dissertation, 1876; Mitchell, Injuries of
Nerves; Mobius, “Pathologie der Sympathicus,” Berlin. klin. Woch., 1884, Nos. 15-19.
Inasmuch as the cervical sympathetic is in close anatomical
connection with the spinal cord, especially with the eighth cervical to
the second dorsal segments (the so-called cilio-spinal centre of
Budge), and as the functions of the sympathetic are dependent upon
the integrity of the spinal cord, it is evident that any lesion of the
nerves uniting it with the cord, or any lesion in the cord itself at the
levels mentioned, may produce symptoms which resemble closely
those of disease of the sympathetic. Thus, cervical pachymeningitis,
myelitis (especially from injury of the cord, or hæmato-myelia), and
diseases of the cervical vertebræ which produce either or both
conditions, may cause a train of symptoms somewhat similar to
those to be described.62 A careful distinction must be made between
primary and secondary disease of the sympathetic, between reflex
and direct symptoms, between lesions in its substance and lesions in
its governing centres in the spinal cord. The symptoms produced by
affections of a reflex or central nature are rarely as numerous as
those of disease of the sympathetic itself. An example of such a
secondary affection is the combination of sympathetic symptoms
occurring in progressive muscular atrophy. And, finally, since mental
action of an emotional nature may cause flushing or pallor of the
face, with profuse sweating and variations in the size of the pupil and
prominence of the eyeballs, as well as palpitation or arrest of the
heart, there is reason to believe that symptoms of sympathetic
disease may be produced by cerebral lesions.
62 Ross, Diseases of the Nervous System, 2d ed., i. 686-688.
PATHOLOGY.—The pathological anatomy of the cervical sympathetic

is obscure. This is probably owing to the fact that the ganglia are
rarely examined, and pathologists have not been familiar with their
histology. Lesions of the cervical sympathetic have been described
in almost every imaginable form of disease, and at one time, when
many obscure conditions were blindly termed sympathetic, the
records were filled with descriptions of fatty degeneration or
interstitial inflammation or pigment deposit in the ganglia. As no
actual symptoms of disease of the cervical sympathetic, as now
understood, were present in such cases, it is impossible to believe
that the lesion was other than hypothetical.
The conditions which have been observed in a few carefully-studied

cases of primary disease have been—(1) A parenchymatous
inflammation of the cells of the ganglia, attended by swelling, loss of
nuclei, granular and fatty degeneration, and by atrophy, together with
a degeneration of the fibres issuing from the cells. (2) A sclerotic
process in the connective tissue in and about the ganglia and in the
nerves, resulting in such an increase in the interstitial tissue as to
compress and injure the cells and axis-cylinders. These may be
observed together in the later stages of the disease. (3) In a number
of cases the capillaries within and about the ganglia have been
found dilated, tortuous, and varicose, and hemorrhages from them
are not rare.
SYMPTOMS.—The symptoms of irritation of the cervical sympathetic

are dilatation of the pupil, widening of the palpebral fissure,
protrusion of the eyeball, pallor of the entire side of the face and
head, with slight fall of local temperature and possibly an increased
secretion of perspiration, and an increased frequency of the heart. It
is rarely that these are all observed in any case, dilatation of the
pupil with slight pallor and rapid pulse being the only signs of
irritation as a rule. Such irritation is a less common occurrence than
might be supposed, many lesions which produce pressure even of a
slight degree on the sympathetic having caused symptoms of a
suspension of its function rather than of an increased activity. This is
doubtless due to the non-medullated structure of the fibres, which
thus lack protection from injury.
The symptoms of destructive disease of the cervical sympathetic are

the converse of those just mentioned, and they are all present when
the part is seriously involved. The patient will then have a marked
contraction of the pupil, which no longer responds to light or to
irritation of the skin of the neck, but may change slightly in the act of
accommodation. It resists the action of mydriatics. The vessels of the
choroid and retina may be dilated, as well as those of the iris, in
which case the patient will feel a sense of weariness on any long-
continued attempt to use the eyes. There is no actual disturbance of
vision, and the cornea is not usually flattened, as was formerly
supposed. There is a noticeable narrowing of the palpebral fissure,
the upper lid falling slightly as in a mild state of ptosis, and the lower
lid being slightly elevated. This is due to the paralysis of the muscles
of Müller in the eyelids, which are controlled by the sympathetic. It is
present in 90 per cent. of the recorded cases, and in many the
apparent size of the eye is reduced a half. Retraction of the eyeball
is a less constant symptom, and one which develops only after the
disease has existed some time. It is due partly to the paralysis of the
orbital muscle of Müller, and partly to the decrease in the amount of
fat in the orbit behind the eye. A marked symptom, and one which is
constant, is a dilatation of the vessels of the face, conjunctiva, nasal
mucous membrane, ear, and scalp. This is attended by redness, a
subjective sense of heat, and an actual rise of local temperature,
which may exceed that of the other side by 1.5° F., measured in the
auditory meatus or nose. This vascular congestion has persisted in
some cases for three years. In others it has been followed much
earlier (in nine months) by a partial or complete return to the normal
condition, and even when the local temperature remains higher on
the affected side, the visible congestion and the sensation of heat
may have disappeared. The dilatation, succeeded by the contraction
(normal tone), of the vessels has led to a division of the disease into
two stages, and in a few cases the affected side has become paler
than the other in the second stage. In both stages the part affected is
less sensitive to changes in the external temperature.
An increased secretion of tears and of perspiration has been

supposed to accompany dilatation of the vessels of the skin of the
head inevitably. This is not a constant symptom, as the recent cases
have demonstrated. And no definite statement of the effect of
disease of the cervical sympathetic on the occurrence of dryness or
dampness of the face can be made, both conditions having been
observed. A difference between the degree of moisture on the two
sides of the face on exposure to heat is usually present. Palpitation
of the heart has been an annoying symptom to the patient in many
cases, and is usually associated with a marked slowing of the pulse.
This was reduced from 74 to 66 in Möbius' case,63 and remained
slow for some weeks. The frequency of the heart may, however, be
increased after the first period of slowing, but never reaches a very
high rate (88 in the case cited). A slight atrophy of the affected side
of the face has been observed in several cases, appearing after the
disease has existed for some time. The muscles of the cheek feel
flabby and are slightly sunken; but the condition does not approach
in severity true facial hemiatrophy, nor is it sufficiently rapid to be
considered due to a trophic disturbance. Changes in the secretion of
saliva, dryness of the nasal mucous membrane, and symptoms
referable to paralysis of the intracranial vessels, such as might be
expected from the result of physiological division of the sympathetic,
have only been occasionally observed. Glycosuria has been noted in
a few cases.64
63 Berlin. klin. Woch., 1884, No. 16.
64 Gerhardt, Volkmann's Sammlung klin. Vorträge, No. 209, “Ueber Angioneurosen,”

p. 11.
COURSE.—The course of the disease has been divided into two

stages, as already mentioned, the majority of the symptoms
remaining permanently from the onset. The second stage is
characterized by the cessation of the dilatation of the vessels, by the
appearance of retraction of the eyeball, and by the development of
slight facial atrophy. In the cases where the sympathetic is
extensively destroyed by the lesion no recovery is possible. When it
is simply divided by a wound there has been a considerable degree
of recovery, probably due to a spontaneous union of the divided
ends and re-establishment of the function. From these facts the
prognosis can be deduced.
DIAGNOSIS.—The symptoms are so characteristic that there is no

difficulty in reaching a diagnosis. The most important point in any
case is to determine the cause, care being taken to consider all the
possibilities already mentioned in discussing the causation. The
symptoms of lesion are always unilateral.
TREATMENT.—If the cause can be removed, an indication for
treatment is afforded. Sources of reflex irritation are to be eliminated.
If the sympathetic has been divided by a wound, it may be well to
unite the cut ends, as in suture of other nerves, although this has not
yet been attempted; otherwise there is little hope from any method of
treatment. Electricity has been applied in vain, and galvanization of
the sympathetic in the neck is now regarded by all good authorities
as useless.
Diseases of the thoracic and abdominal sympathetic ganglia and

cords have been suspected, but nothing definite is known of their
symptoms or pathology; the statements which have recently been
made regarding visceral neurosis not being based upon any cases in
which post-mortem lesions were found.
Trophic Neuroses.
TROPHIC NERVES AND NERVOUS CENTRES.—The nutrition of the body

depends upon the nutrition of the individual cells of which it is made
up. Each cell has the power of appropriating from the blood such
substances as will preserve its existence, enable it to perform its
functions, and produce a successor. Whether this power is inherent
in the cell or is controlled by the nervous system is a question upon
which authorities are divided. Those who hold the first position deny
the existence of trophic nervous centres and of trophic nerves from
those centres to the organs and elements of the body, claiming that
this hypothetical trophic system has not been demonstrated
anatomically, and that the facts urged in its support are capable of
another interpretation. Those who believe in the existence of a
trophic system have been able to demonstrate the existence of fine
peripheral nerve-fibres passing to and ending in individual cells of
the skin, glands, and other organs,65 and have brought forward a
large collection of facts which merit a careful examination.66 They are
as follows:
65 Bericht der Section für Dermatologie, Versammlung Deutscher aerzte, Strasburg,
1885; Vierteljahrschrift für Dermatologie und Syphilis, 1885, 4 Heft, S. 683.
66 “Tropho-neurosen,” Real Cyclopædie f. d. gesammt. Medicin, vol. xiv., 1883; Erb,

Ziemssen's Cyclopædia, xi. pp. 408-423.
ATROPHY.—When a nerve is cut certain changes occur in it which are

known as Wallerian degeneration.67 This affects the peripheral end
of a severed nerve, the peripheral end of a severed anterior nerve-
root, and the central end of a posterior nerve-root. To maintain its
integrity a motor nerve must be in direct continuity with a normal cell
of the anterior cornu of the spinal cord; a sensory nerve must be in
connection with the intervertebral spinal ganglion on the posterior
nerve-root. Nerves which pass between two such ganglia do not
degenerate when cut. The degeneration consists68 in a coagulation
of the myelin in the medullary sheath, a fatty degeneration of the
coagulum, and a gradual absorption of the débris. The axis-cylinder
is compressed, and finally disintegrated, by a mass of protoplasm
which develops about the nuclei of the interannular segments, and
after undergoing fatty degeneration its débris becomes mingled with
that of the myelin, and is also absorbed. The sheath of Schwann,
whose nuclei have in the mean time increased by a process of
subdivision, is partly filled by the protoplasm (from which the new
axis-cylinder develops if regeneration occurs), remaining as a fine
thread of connective tissue when all other traces of the nerve-fibre
have disappeared. There may be a proliferation of cells of the endo-
and perineurium at the same time which aids in the transformation of
the nerve into a connective-tissue strand. This process of
degeneration involves the terminal plates by which the nerves join
the muscles, but the terminations of the sensory nerves—i.e. tactile
corpuscles—do not appear to be affected. The central end of the cut
nerve may display a similar change for a distance not greater than
one centimeter; it usually develops a bulbous swelling of connective
tissue, and retains its conducting power indefinitely.
67 Waller, Philosoph. Transactions, 1850, ii. p. 423; Comptes rendus de l'Acad. de
Sci., 1852-55.
68 Ranvier, Leçons sur l'Histologie de Système nerveux, Paris, 1878; Von
Recklinghausen, Pathologie der Ernahrung, 1883.
Degeneration in the tracts of the spinal cord occurs after various

forms of lesion,69 and is similar in its processes to degeneration in
the peripheral nerves. The increase in the connective-tissue
elements is more noticeable in contrast with the parts unaffected,
and from the density of the tract involved the result has been called
sclerosis. The recent researches of Homen70 have shown that the
process of degeneration begins in the entire length of the affected
tract, and does not proceed from the point of lesion onward, as was
formerly supposed.
69 See Vol. V., “Myelitis—The Secondary Scleroses,” p. 892; Schültze, Arch. für
Psych., xiv. 2.
70 Fortschritte der Medicin, 1885, No. 9.
When a muscle is separated from its connection with the central

nervous system, either by a division of the nerve passing to it or by a
destruction of the cells in the anterior cornu of the spinal cord from
which that nerve arises, it undergoes an atrophy which is peculiar in
being immediate and rapidly progressive, thus contrasting strongly
with the gradual and slighter atrophy from disuse in cases of cerebral
paralysis where the cells mentioned and the nerve-fibres are intact.
There is at first a simple diminution in the number of the fibrillæ of
which the muscular fibre is made up, together with an increase in the
interstitial connective tissue nuclei. Then an albuminoid and fatty
degeneration of the muscular elements occurs, with a proliferation of
muscle-corpuscles or nuclei, and a gradual absorption of the débris.
The interstitial connective tissue then increases rapidly, forming
fibrous bands through the degenerated muscle which compress the
few muscular fibres remaining, until as a result the muscle is
transformed into a mere ribbon of connective tissue without any
power of contractility.71 As these changes go on the electrical
reactions change, the three degrees of reaction of degeneration
corresponding to the three stages of atrophy described.72 These
phenomena of nerve- and muscle-degeneration are observed in
traumatic or idiopathic neuritis, in acute and chronic poliomyelitis
anterior, in general myelitis involving the anterior cornua, and in
bulbar paralysis.
71 Hayem, G., Recherches sur l'Anatomie pathologique des Atrophies musculaires,
Paris, 1873; Ross, Diseases of the Nervous System, vol. i. p. 238.
72 See Vol. V., “Electric Reactions.”
The influence of the nervous system on the nutrition of the bones

has also been ascertained. When a bone is developing, a lesion of
the nerve to it, or of the deeper portion of the anterior cornua of the
spinal cord from which these nerves arise, will modify and partly
arrest its growth. This is often seen in anterior poliomyelitis and in
hemiatrophy of the face occurring in children. In the adult a no less
marked effect is produced, although the results are less noticeable.
A condition known as osteoporosis is caused, consisting of an
enlargement of the Haversian canals and an infiltration of fatty
matter into them and an actual decrease in all the inorganic
constituents of the bone, which loses in weight, becomes thinner and
more fragile, so that spontaneous fractures may occur.73 This
condition has been noticed more frequently in diseases of the spinal
cord than in neuritis; it is said to occur in locomotor ataxia. It has
been found in a few cases of long-standing hemiplegia and also in
dementia paralytica, no explanation of its pathogeny in these
instances, however, being offered. In a case of ataxia with a lesion in
the medulla which involved the nuclei of the fifth, ninth, tenth, and
eleventh nerves on one side, all the teeth of the upper jaw on that
side fell out within a few weeks, those in the lower jaw remaining.74
Changes in the nutrition of the bones have also been recorded in
cases of progressive muscular atrophy in the paralyzed limbs.75
73 Weir Mitchell, Amer. Journ. of the Med. Sci., 1873, p. 113; Charcot, Arch. de Phys.,
1874, p. 166.
74 Demange, Rev. de Médecine, 1882, p. 247.
75 Friedreich, Progressive Muskelatrophie, p. 347, 1873.

The condition of the skin and its appendages is influenced decidedly
by changes in the nervous system, either in the nerves, in the spinal
ganglia, or in the central gray matter. Here it is the sensory nerves
which convey the trophic influence, not the motor nerves, as in the
cases hitherto considered; and when the lesion producing trophic
changes in the skin is central, it is situated in the posterior cornua of
the spinal cord or in the gray matter near the central canal. The
glossy skin seen on the fingers after injuries to the nerves is a type
of such atrophy from disturbance of trophic impulses. Glossy fingers
present a smooth, shining appearance, are dry from the diminution in
the secretion of sweat, feel soft and satin-like to the touch from the
marked thinning of the skin, and frequently show a defective or
irregular growth of the nails, which may be ridged, curved, or
deformed.76 They are red and mottled from accompanying vaso-
motor paralysis, and are usually hot and painful. Changes in the
pigmentation of the skin and hair are recorded as a not infrequent
accompaniment of severe neuralgia and as a result of great mental
anxiety. Thus in several cases of supraorbital neuralgia the eyebrow
on the affected side has turned white; in infraorbital neuralgia the
beard has become gray; and in both the hair has been observed to
fall out.77 The sudden turning white of the hair is ascribed to a
swelling of the hair by air within it.78 In one case, frequently cited, the
hair and nails fell out after a stroke of lightning.
76 Weir Mitchell, Injuries of Nerves. See also Vol. IV. p. 683.
77 Seeligmüller, Lehrbuch der Krankheiten d. Peripheren Nerven, p. 157, 1882.
78 Arch. f. Path. Anat., xxxv. 5, 575, Landois.
When a gland is cut off from its nervous connection with the cord or
cerebral axis by section of its nerves, its function is impaired and its
nutrition suffers, so that after a time it loses weight and undergoes a
progressive total atrophy. This has been proven experimentally in
animals in the submaxillary gland. It has been observed in the
testicle in man after division of the spermatic nerve (Nélaton) and
after destruction of the spinal cord by traumatic and idiopathic
myelitis (Klebs, Föster).79 The sweat-glands are known to be under
the control of a central nervous mechanism, as cases of
hyperidrosis, anidrosis, and chromiodrosis prove;80 and an atrophy of
them and of the sebaceous glands has been observed81 after
nervous lesions.
79 Cited by Samuel, Realcyclop., loc. cit. See also Obolensky, Centralblatt für med.
Wissen., 1867, 5, 497.
80 See Vol. IV. pp. 583-586.
81 See Vol. IV. pp. 683 et seq.
Progressive hemiatrophy of the face is treated elsewhere. The

following case of progressive hemiatrophy of the entire body may be
mentioned here: A boy, aged fourteen, dislocated his ankle, which in
a few days became swollen, red, hot, and painful. The inflammation
extended up the leg, but did not involve the knee, and soon
subsided. After a short time the foot began to atrophy. The atrophy
extended up the leg, and involved the thigh; it then progressed to the
trunk and the arm, and lastly to the face on the affected side, until in
the course of two years there had developed a unilateral atrophy of
the entire body. Muscles, fat, and bones were all affected, but no
difference in the skin or hair of the two sides was noticed. Fibrillary
tremors were present in the muscles. The electric reactions were not
altered, but were gradually lost. There was a hypersensitiveness to
touch and to cold, but no other sensory disturbance. The boy was
alive and fairly well when the case was reported.82 It is unique.
82 Heuschen, Schmidt's Jahrbuch., vol. cxcviii. p. 130.
These various instances of atrophy cannot be ascribed to simple

disuse, since they differ markedly in their pathological changes and
in the rapidity of their progress from such atrophy. Nor are they to be
referred to vaso-motor disturbances, since in many cases no
vascular changes are evident. Their distribution in the body often
corresponds exactly with that of peripheral nerves, and they
accompany nerve lesions too frequently to be explained on any
theory of coincidence. There are many authorities, however, who
refuse to ascribe them to a lesion of trophic nerves.83 In regard to the
degeneration of nerves it is said that each nerve axis-cylinder is a
part of the nerve-cell from which it arises, and hence destruction of
the cell or division of the cylinder, by disturbing the unity of
existence, results in the death of the part. The fibre shares all the
changes of nutrition which the nerve-cell undergoes, and if
separated from it necessarily perishes. To this it is replied that
trophic paths and motor paths are distinct at some points in their
course, at least in the central nervous system, since each can be
affected alone. Erb, who has studied this subject carefully,84 believes
that trophic are distinct from motor centres in the spinal cord, but that
both impulses may be conveyed by the same axis-cylinder in the
peripheral nerves—a middle ground which is widely accepted. It is
now known that each axis-cylinder is made up of several fibrils, so
that this theory gains probability. This would also explain the
occurrence of atrophy in the muscles, the trophic centres being
affected when the muscle atrophies, and unaffected when it is
paralyzed without atrophy. Mayer, however, denies this explanation
of the muscular atrophy, holding that the motor system, cell, nerve,
and muscle-fibre, forms a nutritive as well as functional unit, and that
the simple suspension of function, by interfering with the special
conditions of nutrition attendant upon physiological excitement, is
competent to cause a pathological change. To this it is replied that
the parts of the motor system are not interdependent, since disease
of the muscle does not produce degeneration of the nerve and of the
cell, and the fact of a degeneration in a peripheral direction alone is
evidence of central trophic influence. The attempt to ascribe trophic
changes in the skin, nails, and hair to vaso-motor disturbance has
been equally unsuccessful in covering all the observed cases.
83 See Handfield Jones, St. George's Hospital Reports, 1868, vol. iii. pp. 89-110;
Sigmund Meyer, Hermann's Handbuch d. Physiol., ii. Th. 2, “Trophische Nerven,”
1879; Gowers, Diseases of the Brain, 1885, p. 4.
84 Arch. f. Psych., v. S. 445, 1875; also Ziemssen's Cyclo., vol. xiii. p. 117 (Amer.
trans.); also Deut. Arch. f. klin. Med., v. S. 54.
FIG. 58.
Diagram of the Arrangement and Connection of Motor and Trophic

Centres and Fibres in the Spinal Cord and Motor Nerve (after Erb): a,
motor fibre of spinal cord from the brain to d, the motor cell, which is
joined to the muscle m by the motor nerve; b, trophic cell in the spinal
cord for the muscle, to which it is joined by the trophic fibre bʹ; c, trophic
cell in the spinal cord for the motor nerve, to which it is joined by the
trophic fibre cʹ; s, a fibre bringing sensory (reflex) impulses to the cell.
If d is destroyed, the fibres from b and c perish with it, and the result is
paralysis and atrophy of the muscle and degeneration in the motor nerve
—e.g. poliomyelitis anterior. If b is destroyed, the muscle atrophies, and
paralysis is a secondary result—e.g. progressive muscular atrophy. If c is
destroyed, the nerve degenerates, and paralysis and atrophy of the
muscle are secondary results—e.g. neuritis with reaction of
degeneration. If a is destroyed, voluntary power is lost, but reflex power
remains, and no atrophic changes occur—e.g. lateral sclerosis. If the
motor nerve is cut between d and m, the result is the same beyond the
division as when the motor cell is destroyed.
HYPERTROPHY.—Trophic changes are not limited to the process of

atrophy. There are conditions of hypertrophy of supposed nervous
origin. Samuel considers the hypertrophy of one testicle which
attends atrophy of the other from section of its nerve as an example
of this. It has been ascertained that one kidney hypertrophies when
the other is atrophied or extirpated. When the spleen is removed the
lymphatic glands increase in size. But these facts are capable of
another explanation—viz. that increased demand upon the organ
leads to its increased growth. Hypertrophy of the skin and of the
tongue is seen in cretins in contrast with the deformity of the body
and atrophy of the limbs. A hemihypertrophy of the face has been
noticed in several cases, the counterpart of hemiatrophy; and in one
case a unilateral hypertrophy of the entire body was observed.85 The
local thickening of the skin known as ichthyosis hystrix, and other
hypertrophies of the skin, certain deposits of pigment, and vitiligo,
have been ascribed to nervous causes. Mitchell has recorded cases
of abnormal growth of the nails and hair after injuries to the nerves,
and similar phenomena have followed central lesions. He has also
described a thickening of the skin of the first three fingers and of the
back of the hand following a wound of the brachial plexus. These
conditions of the skin and its appendages indicate an abnormal
activity in the cells of the affected part, a rapid metabolism and
reproduction, resulting in an undue production of tissue, apparently
dependent on nervous impulses reaching the cells from a distance.
The insane ear may be mentioned in this connection as a trophic
disturbance due to central lesion.
85 Ziel, Virchow's Archiv, xci., S. 92.
MYXŒDEMA (cachexie pachydermique) is a disturbance of nutritive

processes characterized by a production of mucin, which is
deposited in all the tissues of the body, but especially in the
subdermal connective tissue.86 It is considered by the majority of
authors a trophic neurosis, and is therefore considered here.
86 Sir William W. Gull, “On a Cretinoid State supervening in Adult Life,” Trans. Clin.
Soc. London, 1874, vol. vii. p. 170; Ord, “On Myxœdema,” Med.-Chir. Trans., 1878,
vol. lxi. p. 57; Mahomed, Lancet, 1881, ii. No. 26; Hadden, Brain, 1882; W. A.
Hammond, Neurological Contributions, 1881, i. p. 36; Ballet, Archives de Neurologie,
1881, vol. iii. p. 30; Schmidt's Jahrbucher, vol. clxxxix. p. 30, and cxcviii. 264; “The
Brown Lectures,” Victor Horseley, Lancet, Jan., 1886.
PATHOLOGY.—In the few autopsies which have been made an

increase in the connective tissue of all the organs has been found, in
the meshes of which a thick, transparent, slimy substance (called
animal gum), consisting of mucin, is present. This may compress
and destroy the parenchyma of the organs involved. There is also
found a thickening of the coats (adventitia and media) of the vessels.
An atrophy of the thyroid gland has occurred in every case, and
experimental extirpation of the thyroid in animals produces
symptoms so nearly identical with those of myxœdema that this is
considered the chief pathological feature of the disease. Whether
this atrophy is due to a compression by the mucin deposited, or is
due to a disease of the trophic centres of the thyroid in the medulla,
or is a primary affection of the gland, remains to be determined.
ETIOLOGY.—The actual causation is unknown. Cold and mental shock

have been considered exciting causes in some cases. Women are
much more liable to the disease than men, and it develops after the
age of forty in the majority of cases. It may occur in childhood and
result in a cretinoid state. Syphilis and tuberculosis do not appear to
be etiological factors.
SYMPTOMS.—The disease begins gradually, and the nervous
symptoms or the local œdema may appear together or in
succession. The patient notices a thickening of the skin, which
becomes dry, rough, and scaly. The thickening is uniform and
involves the entire body. It is most marked where the subdermal
connective tissue is loose, as in the cheeks, lips, eyelids, and in all
parts where the skin is thrown into folds. The hands and feet do not
escape. The thickened skin is hard, and does not pit on pressure,
thus differing from ordinary œdematous swelling. It appears of a
waxy color, and is free from perspiration, the sweat-glands becoming
atrophied from pressure. The hair may fall out or become woolly and
brittle, and may change its color. In a few cases spots of pigment
have appeared on various regions.87 The nails are brittle. The teeth
are carious. The mucous membranes show similar changes, and the
mouth and tongue, rectum and vagina, may be so swollen as to
impair their respective functions. Digestive disturbances,
constipation alternating with diarrhœa, and uterine hemorrhages,
which occur, are ascribed to this cause. Albumen is occasionally
found in the urine, but is not a constant symptom. The nervous
symptoms are constant. The patients complain of paræsthesiæ and
anæsthesia of the extremities or over the entire body, and the
special senses may be impaired, as well as the tactile sense. They
are very liable to severe attacks of neuralgia. They suffer from
subjective sensations of cold, and are easily affected by changes of
temperature. Motion is interfered with; tremors occur early;
movements become slow and awkward; the gait is unsteady; the
voice is rough and nasal; but no true paralysis or muscular atrophy
has been observed. The patella-tendon reflex is occasionally lost,
but not in all cases.
87 Allan McLane Hamilton, Journ. Nerv. and Ment. Dis., 1885, April, p. 180.
These symptoms have been ascribed to the pressure of the mucin

upon the terminal filaments of the nerves, and also to changes in the
central nervous system. That the latter theory is probably correct is
shown by the occurrence of mental symptoms in the majority of
cases. The patients become apathetic and all mental action is slowly
performed. Indifference to surroundings, loss of memory, and
inability to concentrate the attention may be succeeded by transient
delirium, hallucinations, and occasionally by delusions of
persecution, and the patient finally lapses into a state of imbecility. If
the disease develops in early life, education is impossible, and the
patient remains in an infantile condition.
Whether the changes in the nervous system are due to pressure by

deposit of mucin (Hadden), or are due to an altered nutrition of the
most delicate tissues of the body consequent upon the general
metabolic derangement (Horseley), is undetermined. In experimental
myxœdema the degenerative processes have been found in the
nerve-cells.
There are no symptoms referable to the heart or lungs, and if

cirrhosis of the kidney and liver develop, their symptoms supervene
upon and are secondary to those of myxœdema. High arterial
tension has been noticed in the majority of the cases.
The COURSE of the disease is a chronic one, and is progressive.

There are, however, intermissions in the severity of the symptoms in
some cases. Recovery does not occur.
DIAGNOSIS.—The diagnosis from the accumulation of fat is made by

observing the thickening of the nose, lips, fingers, and tongue, and
the changes in the skin and its appendages. Scleroderma is not
universal like myxœdema. In scleroderma the skin is harder and
more adherent to subjacent parts, is not transparent and waxy, and
the nervous symptoms are wanting. Cretinism seems to be closely
allied to myxœdema, but is only observed before the age of seven
and is accompanied by hypertrophy of the thyroid gland.
TREATMENT.—The treatment is only palliative. Simple nutritious diet,

especially milk diet, with the use of such tonics as iron and quinine,
has been found useful. The progress of the disease is hastened by
exposure to cold, and in a very warm climate the symptoms may
remain stationary for several years. Jaborandi or pilocarpine has
been used in some cases with a moderate degree of success. Nitro-

Textbook Fundamentals of Male Infertility Sherman Silber Ebook All Chapter PDF

Uploaded by

Copyright:

Available Formats

You might also like

Textbook Fundamentals of Male Infertility Sherman Silber Ebook All Chapter PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Textbook Fundamentals of Male Infertility Sherman Silber Ebook All Chapter PDF

Uploaded by

Copyright:

Available Formats

Fundamentals of Male Infertility

Male Infertility A Clinical Approach 1st Edition

Andrological Evaluation of Male Infertility A

Molecular Signaling in Spermatogenesis and Male

Male Infertility in Reproductive Medicine: Diagnosis

A Compendium of Neuropsychological Tests: Fundamentals

Male Rape is a Feminist Issue Feminism Governmentality

Textbook of Male Genitourethral Reconstruction

Infertility and Intimacy in an Online Community Paulina

Sherman Silber, M.D.

With Science Editor:

ISBN 978-3-319-76522-8 ISBN 978-3-319-76523-5 (eBook)

Library of Congress Control Number: 2018941091

© Springer International Publishing AG, part of Springer Nature 2018

Printed on acid-free paper

It is always intriguing to write a foreword for a special groundbreaking book. It is

Brussels, Belgium Paul Devroey

Fig. 4 Ureteral bladder anastomosis in rat

Fig. 11 This micro-

Fig. 12 A picture of the

Fig. 13 The first large free

Fig. 15 The original

extravasculation in the epididymis and secondary epididymal blockage. Furthermore

Fig. 18 The author’s end to end specific tubule vasoepididymostomy

secondary epididymal obstruction, we realized that we needed to achieve better

Fig. 19 (a–d) Modified end-to-side vas to epididymostomy

St. Louis, MO Sherman Silber

Part I Basic Science of the Testis

Part II Evaluation and Treatment of Male Infertility

10 Treatment of Male Infertility������������������������������������������������������������������ 59

15.3 Varicocelectomy and Sperm Count�������������������������������������������������� 146

Part III New Frontiers

NATURE.—The nature of the disease is a matter of deduction from the

DIAGNOSIS.—The diagnosis rests upon the development of vaso-

PROGNOSIS.—Life is not endangered by this disease, no fatal cases

TREATMENT.—The methods of treatment have varied, and none are

The pain occurring in the early stages is often so severe as to

Diseases of the Cervical Sympathetic.

ETIOLOGY.—Diseases of the cervical sympathetic ganglia or cord may

PATHOLOGY.—The pathological anatomy of the cervical sympathetic

The conditions which have been observed in a few carefully-studied

SYMPTOMS.—The symptoms of irritation of the cervical sympathetic

The symptoms of destructive disease of the cervical sympathetic are

An increased secretion of tears and of perspiration has been

64 Gerhardt, Volkmann's Sammlung klin. Vorträge, No. 209, “Ueber Angioneurosen,”

COURSE.—The course of the disease has been divided into two

DIAGNOSIS.—The symptoms are so characteristic that there is no

Diseases of the thoracic and abdominal sympathetic ganglia and

TROPHIC NERVES AND NERVOUS CENTRES.—The nutrition of the body

66 “Tropho-neurosen,” Real Cyclopædie f. d. gesammt. Medicin, vol. xiv., 1883; Erb,

ATROPHY.—When a nerve is cut certain changes occur in it which are

Degeneration in the tracts of the spinal cord occurs after various

70 Fortschritte der Medicin, 1885, No. 9.

When a muscle is separated from its connection with the central

72 See Vol. V., “Electric Reactions.”

The influence of the nervous system on the nutrition of the bones

74 Demange, Rev. de Médecine, 1882, p. 247.

75 Friedreich, Progressive Muskelatrophie, p. 347, 1873.

Brussels, Belgium Paul Devroey

St. Louis, MO Sherman Silber

Part I Basic Science of the Testis

10 Treatment of Male Infertility�� 59

15.3 Varicocelectomy and Sperm Count�� 146

Part III New Frontiers