The International Council on Infertility Information Dissemination, Inc

The Function of Endogenous Platelet Activating Factor (PAF) in Human Sperm

Blackboard with MALE INFERTILITY on it

by

Slee L. Yi1, Julia M. Robison1, and William E. Roudebush1,2

1University of South Carolina School of Medicine Greenville, 2Fertility Center of the Carolinas, Department of Obstetrics & Gynecology,
Greenville Health System, Greenville, South Carolina

 

Eight to ten million couples are afflicted with infertility in the United States. Infertility can be caused by a number of factors. Not only females but also males can have problems with infertility. Male infertility is the primary culprit in ~25% of these couples, and is a factor in additional 20% of these couples. There are several prerequisites that must be met for male fertility. Defects in any of these will result in infertility.1

Platelet Activating Factor

Platelet-activating factor, commonly known as PAF, is a phospholipid involved in a number of biological activities. PAF was first discovered and studied in rabbits over thirty years ago.2 It is known to be present in several mammalian species including mice, bulls, boars, and even humans.1,3-5 Since its discovery, PAF has been found to play a significant role in reproductive physiology.1

Research shows that PAF plays a very important role in sperm motility. It does this through binding to PAF receptors found in the sperm membrane.  Reports indicate that PAF receptors exist at the midpiece (neck) and the equatorial (head) regions of the sperm. Binding at these locations leads to an increase in fertility rate. Conversely, when these receptors are abnormal or appear at abnormal locations, fertility is compromised.1,6

During the last few years, scientists have discovered different amounts of PAF and PAF receptors in motile and non-motile sperm. Studies have found that motile sperm contain a greater number of PAF receptors than do non-motile sperm.  Interestingly as well, the actual PAF concentration in motile sperm appears to be less compared to non-motile sperm. This indicates that non-motile sperm contain more PAF than motile sperm because they are not able to use it. Motile sperm shows less PAF content because these cells are using it.1,7 Fertility may be further compromised in the presence of PAF antagonists.  These are substances that compete against PAF at the receptor site, which causes a decrease in PAF binding and can resuls in infertility. Although the exact mechanism for this is unclear, its importance is substantial. 1,8-10

The active form of PAF is produced inside the male sperm cell through a cycle of reactions. The enzyme responsible for synthesizing active PAF is also found in the sperm cell itself.1,11 However, there are enzymes that disable PAF by converting it into an inactive form.1,12These disabling agents are present in seminal fluid.13 The process therefore requires sperm to be separated from the seminal fluid in order for PAF to become active and cause increased sperm motility. This separation occurs when sperm is ejaculated – typically into the vagina, where it will swim away from the fluid and enter the uterus. Once sperm is separated from the seminal fluid, PAF can be synthesized and subsequently bind to its receptors on the sperm cell membrane. Once the sperm responds to PAF, its motility dramatically increases, and it becomes ready to fertilize the egg.14 This process is called capacitation. As expected, sperm cells that have not yet capacitated are found to contain lower levels of PAF.1,12 That is because, as explained, the seminal fluid contains substances which prevent active PAF from being synthesized. On the other hand, capacitated sperm cells are found to contain higher levels of PAF. When active PAF is present in the sperm cell and is able to appropriately bind to its receptors, it improves interactions between sperm and egg, and positively affects pregnancy outcomes.1 Determining the active PAF content and its interaction with receptors could potentially be a beneficial diagnostic tool for male infertility. Further research should be conducted to better understand PAF and how PAF could possibly be useful in clinical applications such as in vitro fertilization (IVF) in the near future.1,15

 

References

1. Roudebush WE. Seminal platelet-activating factor. Semin Throm Hemost 2007;33:69-74

2. Benveniste J, Henson PM, Cochrane CG. Leukocyte dependent histamine release from rabbit platelets: the role of Ig-E, basophils, and platelet-activating factor. J Exp Med 1972;136:1356–1376
3. Parks JE, Hough S, Elrod C. PAF activity in bovine sperm. Biol Reprod 1990;43:806–811
27.
4. Minhas BS, Kumar R, Ricker DD, Robertson JL, Dodson MG. The presence of platelet activating factor-like activity in human sperm. Fertil Steril 1991;55:372–376
28.
5. Mook JL, Diehl JR, Mathur RS, Roudebush WE. Presence of platelet-activating factor in porcine sperm and uterine fluid. Theriogenology 1998;49:351
6. Harper MJK. Platelet activating factor: a paracrine factor in 
preimplantation stages of development? Biol Reprod 1989; 40: 907–913

7. Purnell ET, Roudebush WE. Platelet-activating factor activity levels (ligand and receptor transcript content in sperm: motile versus nonmotile. In: Proceedings of the VIIth International Congress of Andrology. Montreal, Quebec: Andrology in the 21st; 2001:71-76.

8. Reinhardt JC, Cui X, Roudebush WE. Immunofluorescent evidence of the platelet-activating factor receptor on human spermatozoa. Fertil Steril 1999;71:941–942
9. Roudebush WE, Ito C, Purnell E, Cui X. Presence of platelet-activating factor and its receptor in baboon (Papio spp) spermatozoa. Int J Primatol 1999;20:273–280
10. Roudebush WE, Wild MD, Maguire EH. Platelet-activating factor receptor expression in human sperm: differences in mRNA content and protein distribution between normal and abnormal sperm. Fertil Steril 2000;73:967–971

11. Bennet PJ, Moatti JP, Mansat A, et al. Evidence for the activation of phospholipases during acrosome reaction of human sperm elicited by calcium ionophore A23187. Biochim Biophys Acta 1987;919:255–265

12.  Letendre ED, Miron P, Roberts KD, Langlais J. Platelet- activating factor acetylhydrolase in seminal plasma. Fertil Steril 1992;57:193–198

13. Gujarati VR, Naukam RJ, RamaSastry BV. Enzymatic deacetylation and acetylation of ether phospholipids related to platelet-activating factor in human semen with short and long liquefaction times. Ann N Y Acad Sci, 1987, 513:583–585.

14. Davis BK. Timing of fertilization in mammals: Sperm cholesterol/phospholipid radio as a determinant of the capacitation interval. Proceedings National Academy of Sciences of the United States of America. 1981, 78:7560-7564.

15. Toledo AA, Mitchell-Leef D, Elsner CW, Slayden SM, Roudebush WE. Fertilization potential of human sperm is correlated with endogenous platelet-activating factor content. J Assist Reprod Genet 2003; 20:192–195.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

News Flash - Patient has successful Pregnancy following Uterine Transplant

First Uterine Transplant

First Uterine Transplant

Professor Mats Brannstrom and colleagues from the University of Gothenburg and Stockholm IVF announced the birth of a healthy baby to a patient following a uterine transplant. The announcement came over the weekend ahead of scheduled publication in the Lancet. Dr. Brannstrom, who published much of the preliminary work on uterine transplant in Fertility and Sterility, will be giving the Society of Reproductive Surgeons Plenary Lecture at the ASRM Annual Meeting in Honolulu on Monday, October 20.

For more information:

First Uterine transplant-gives-parents-a-healthy-baby

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61728-1/abstract

http://www.pennlive.com/nation-world/2014/10/swedish_woman_gives_birth_afte.html

PCOS Video from Fertility Centers of Ilinois

This is a very good video featuring doctors from Fertility Centers of Ilinois and 6 patients who  suffer with PCOS. 

 

PCOS can be managed but you need to understand the signs and get help from a Reproductive Endocrinolgist

Dr. George Koulianos Speaks to Elective Single Embryo Transfer

Elective Single Embryo Transfer. Is it right for you video clip with Dr. George Koulianos

INCIID Professional member, Dr. George Koulianos speaks to Elective Single Embryo Transfers. Is it right for you?

Intracystoplasmic Sperm Injection (ICSI) Video with Dr. Robert Anderson

Video of ICSI with Dr. Robert Anderson

 

Dr. Robert Anderson, an INCIID Professional Member, explains the use of ICSI. An ICSI procedure is filmed under the microscope.

 

PGD Video Clip with Dr. Robert Anderson

 

PDG is Pre-implantation Genetic Testing. Dr. Robert Anderson , INCIID Professional Member Explains the PGD.

 

Testing Anti-Mullerian Hormone to Determine Egg Reserves by Scott Roseff, MD

Golden egg sitting amoung ordinary white eggs

Golden egg sitting amoung ordinary white eggsEGG QUALITY starts declining when a woman is in her mid-20's!

There is a slow decline in quality from about age 24 to age 30, followed by a fairly quick decline between age 30 and age 35, with a rapid decrease between ages 35 and 40. And, over age 40, egg quality is generally quite poor. All of this may make it difficult to get pregnant...

OVARIAN RESERVE describes a woman's capacity to produce a reasonable quantity of good quality eggs. Of course, measuring a woman's ovarian reserve is very important in determining why someone may not be getting pregnant, as well as in finding out the ease (if she has good eggs) or difficulty (if she has poor eggs) with which a pregnancy may be realized.

Women with normal ovarian reserve (good eggs) may conceive via simple therapies (such as timed intrauterine insemination), while women with abnormal ovarian reserve (poor eggs) may require in-vitro fertilization (IVF) or even IVF with donor eggs. Until now, we have only been able to INDIRECTLY measure a woman's ovarian reserve via a cycle day 3 FSH/estradiol blood test, or through a "Clomiphene Citrate (Clomid) Challenge Test", or CCCT. These tests measured the brain's hormones which were INDIRECTLY affected by the ovary's egg quality. While these tests were the best we had, we now have a more modern and sensitive blood test which DIRECTLY measures a woman's ovarian reserve!

The human egg is "housed" inside a structure called the follicle. The follicle is comprised of specialized cells called granulosa cells. The granulosa cells produce a specific hormone directly and predictably linked to egg quality, and that hormone is called AMH. While other means of examining ovarian reserve may offer indirect, and possibly less accurate, less specific, and less predictive tests of egg quality (such as cycle day 3 FSH/estradiol levels and the CCCT), many reproductive endocrinologists believe women are better served by examining their AMH level -- a more direct, more accurate, more specific, and more predictive test of egg quality.

The AMH test has been found particularly useful in the following clinical situations: Women who either need a Clomiphene Citrate Challenge Test (CCCT) or previously had a CCCT and want to confirm/refute the results; Women of advanced reproductive age (35 years or older); Any women with a diagnosis of "unexplained infertility"; Women who have shown a poor response to ovulation induction with either Clomid/Serophene or injectable fertility drugs; Women who have been told they need IVF with donor eggs -- a normal AMH level may permit them to do IVF with their own eggs, while an abnormal AMH level may confirm the need for IVF with donor eggs. If you have individual questions about this article, please feel free to ask them on the General Infertility Medical forum: moderated by Dr. Scott Roseff.

Sonohysterography: A safer alternative to hysterography

Sonohysterography ("SHG") is an ultrasound-monitored procedure similar to a hysterosalpingogram ("HSG"), and is used to detect abnormalities of the uterus and fallopian tubes or tubal blockage. The indications for its use overlap with those for an HSG. Under these circumstances, it no doubt offers a safer alternative to the conventional HSG.

 

Conventional hysterosalpingography is generally performed in a radiology department. It usually involves:

  • The placement of a speculum into the vagina through which a catheter is positioned in the uterus;
  • Radiographic contrast material ("dye") is injected into the uterine cavity, and
  • Several X-rays of the pelvis are taken.

 

There is exposure to radiation and the contrast material contains iodine.

Sonohysterography can be performed as an office procedure. It usually involves:

  • The placement of a speculum into the vagina through which a catheter is positioned in the uterus;
  • A saline solution is injected into the uterine cavity, and
  • At the same time, a transvaginal ultrasound is being performed

 

There is no radiation and no iodinated contrast material involved.

Either procedure can be associated with discomfort. In general, the SHG is more comfortable than the HSG because saline may be less irritating than radiographic contrast material.

Sonohysterography can be used to evaluate the endometrium and Fallopian tubes. For endometrial evaluation, SHG plays a role in an infertility workup.

 

The injection of saline into the endometrial canal (uterine cavity) acts to separate the two sides of the endometrium and improve the visualization of masses, such as polyps. In addition, the saline acts as a contrast material which can make abnormal intraluminal structures, such as synechiae (adhesions), visible. Submucous myomas (fibroids which displace the endometrium) may be better evaluated when an SHG is performed.

 

An SHG can also be employed to evaluate the Fallopian tubes, especially for patency.In my experience, color Doppler imaging improves the ability to detect tubal patency. When the saline is injected, some of it may be seen flowing from the tubes into the pelvis, a finding that confirms patency.

 

Sonohysterography, in my opinion, is an excellent procedure for evaluation of the endometrium and tubal patency. It has the added advantages of no radiation exposure, no iodinated contrast injection (which can be associated with increased discomfort and allergic reactions), the potential for fewer complications. And SHG offers the advantage that ultrasound of the uterus, ovaries and pelvis can be performed at the same time. Thus, uterine masses and other abnormalities may be discovered which would have been missed during a conventional HSG.

 

However, to evaluate the Fallopian tubes for more than just patency the HSG gives better information. How frequently this type of evaluation is necessary depends on the way a physician practices and how you as his/her patient presents. It can also be argued that HSG is better than SHG for determining patency; however, it should be noted that it can also be argued that SHG is better than HSG. Each procedure has its proponents and opponents. Many, if not most, infertility physicians are unfamiliar with the performance and interpretation of this study.

 

Some infertility physicians may choose not to refer a patient to another location and lose the income generated from performing and/or interpreting a test which they cannot or do not perform.

Many, if not most infertility physicians, rely on ultrasound techs to perform and essentially interpret the ultrasounds (realistically speaking). These physicians (possibly the techs, too) may be unwilling to assume the perceived risks of performing an SHG.

 

Some infertility physicians may not have the equipment necessary to perform color Doppler imaging which is very helpful, though not completely necessary.

If your doctor suggests an HSG, it may be to your advantage to ask about SHG. She/he should be more than willing to discuss the options with you.

 

Dr. Michael Applebaum is a Board Certified Radiologist whose practice is limited to Diagnostic Ultrasound. He is an internationally recognized authority in Infertility Ultrasound. He can be reached at (312) 337-0732. His Website is located at http://www.drapplebaum.com.

 

Understanding and Managing Endometriosis by W. Paul Dmowski, M.D., Ph.D.

Understanding and managing endometriosis 
by W. Paul Dmowski, MD, PhD

 

Endometriosis is a disease affecting 5.5 million women in the U.S. and Canada, and is characterized by the growth of the uterine lining (endometrium) outside of the uterus. Uterine endometrium during the first half of the menstrual cycle increases in thickness, and during the second half acquires a spongy-like consistency to facilitate embryo implantation. 

If there is no pregnancy, uterine endometrium sheds along with the menstrual blood during the menstrual period. The same cyclic changes occur also in the endometrium of endometriosis, causing bleeding into the abdomen or into other organs, inflammatory reaction, development of adhesions (scar tissue), or appearance of cysts filled with blood, which over time, acquires a consistency of liquid chocolate (chocolate cysts). These cyclic changes in endometriosis are responsible for symptoms of the disease such as:

  • Painful menstrual periods
  • Pain during or after urination
  • Pelvic pain unrelated to menstruation
  • Heavy, prolonged menstrual periods
  • Pain during and after sexual intercourse
  • Pain during or after bowel movements, and
  • Infertility.

 

The frequency and intensity of these symptoms varies, and there is no direct relationship between symptoms and severity of endometriosis. Some women have advanced endometriosis and few, if any, symptoms. Others have severe symptoms with minimal disease. The intensity of symptoms is most likely related to the local inflammatory reaction and production of substances such as prostaglandins and cytokines by the endometriotic cells and cells of the immune system.

Endometriotic lesions, although benign, may spread like cancer from the reproductive system to other organs and sometimes even to distant locations away from the pelvis. We have seen women with endometriosis of the bladder, bowel, liver, lungs, arms, thighs, and even brain. If endometriosis spreads outside of the pelvis, it can cause generalized symptoms and/or symptoms of pain or bleeding referred to other organs. In general, any symptom or change in the body that undergoes cyclic changes coincidental with the menstrual cycle, should be suspect of being endometriotic in origin.

 

Misplaced endometrial cells are common 
For more than 30 years, Institute for the Study and Treatment of Endometriosis, which is affiliated with the Oak Brook Fertility Center, has been in the forefront of endometriosis research. Our studies indicate that during the menstrual period, blood and fragments of shed endometrial tissues are transported through fallopian tubes into the abdomen in all women.

In healthy women, these misplaced cells are programmed to die (undergo apoptosis) and are removed by the cells of the immune system (macrophages). In about 10 percent of women, apoptosis and the ability of macrophages to remove misplaced endometrial cells is impaired. The misplaced cells are allowed to survive and implant. Typically they implant on the peritoneal surfaces (lining of the abdomen), in the anterior and posterior cul-de-sacs (anterior is between uterus and urinary bladder, posterior is between uterus and rectum), on the ovaries, and on other abdominal organs. Following implantation, endometrial cells divide, multiply, and form typical endometriotic lesions. Changes in endometrial apoptosis and in the immune system that lead to the development of endometriosis may be transmitted genetically from mother-to-daughter or may be acquired as a result of the environmental effect on the immune system.

 

Diagnosing Endometriosis 
Endometriosis can be suspected based on characteristic symptoms, physical examination findings, changes on pelvic ultrasound, CT scans, or x-rays. However, other diseases may give similar findings and the only way to diagnose endometriosis is through a surgical procedure --- laparoscopy or laparotomy. The diagnosis must be confirmed by microscopic examination of the tissue. Not every lesion having a visual appearance of endometriosis is actually endometriotic and sometimes atypical lesions may be endometriotic in nature. Your laparoscopic surgeon should take a biopsy to confirm his visual diagnosis. He should also be able to assign a score for the size, depth, and location of endometriotic lesions which is the basis for classifying endometriosis as Stage I, II, III, or IV, with Stage I being the minimal and Stage IV the most advanced. Endometriosis is a progressive disease which impairs fertility, tends to come back after treatments, and lasts as long as the ovarian function, that is, until menopause. Therefore, prompt definitive diagnosis and staging are extremely important for the lifelong treatment, recurrence prevention, and family planning.

Laparoscopy is a minor surgical procedure performed under anesthesia on an outpatient basis. An experienced laparoscopic surgeon should be able to resect or destroy endometriotic lesions with electrical current or laser at the time of laparoscopy. Alternative treatments include various types of hormonal medications, the purpose of which is to suppress ovarian function and stop menstrual cycles. Without menstrual bleeding, endometriotic lesions heal and gradually disappear. Large chocolate cysts and adhesions may have to be removed surgically.

 

Treatment 
The choice of treatment in endometriosis depends on several factors such as:

  • Woman’s age
  • Severity of symptoms
  • Fertility status
  • Stage of the disease
  • Prior treatments, if any,
  • Treatment response and side effects, if any.

 

These factors, as well as patient-specific indications and contraindications, advantages and disadvantages, and risks and benefits of different treatment options need to be thoroughly discussed and considered prior to treatment selection.

At the Endometriosis Institute, our objective is to help patients select the treatment option that is most appropriate for her case. Our overall goal is to remove or suppress endometriosis, to delay its recurrence, control its progression, and to take care of its symptoms without adversely affecting a woman's fertility and without exposing her to undesirable side effects of treatments. Different women may respond differently to the same treatment, both in terms of the effectiveness and side effects, and there is no one treatment that would be effective in all women.

W. Paul Dmowski, M.D., is the Director of the Oak Brook Fertility Center and the Director of the Institute for the Study and Treatment of Endometriosis in Oak Brook, Illinois.

 

Editor's Note: The Institute for the Study and Treatment of Endometriosis always has several ongoing clinical research projects. Frequently, the Institute has new medications for clinical trials before they become generally available. Such clinical studies, including medications, are often at no charge to the patient. For more information about participating in a study, please call 630-954-0054.

 

Thatcher's Thoughts

Age and Aging

Assisted Reproductive Technologies (ART)

Cancer

Cardiovascular

Hormones

Insurance & Infertility

Diabetes and Other Metabolic Problems

Menopause

Menstration

Pregnancy Loss and Miscarriage

Polycystic Ovarian Syndrome (PCOS)

Drug Therapy

Surgery

Smoking

Obesity

A Tribute to Sam Thatcher, M.D., Ph.D.
Perhaps the best description of Sam Thatcher is one paraphrased in his book Making a Baby, co- written with Debra Fulghum Bruce: “He was a polar bear of a man, … a rumpled Ivy League professor who returned home to start his own practice… (with) a style that was a combination of therapist, detective and scientist.” His untimely death was a loss to infertility patients everywhere. Sam always did the right thing for his patients and will be terribly missed. Read the tribute the man who brought the most economical IVF in the US to his patients.

 

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