It has been a year this week that a doctor at the University of Chicago told us that we would never have children. As devastating as that news was, we didn't give up. And as luck would have it, God placed into our lives a doctor by the name of Sherman Silber. From the very first day we contacted your office, your staff gave us hope! Something we didn't have much of in the past.
The journey was long and emotional, but nothing worthwhile is ever easy. We are just very happy that the outcome is two wonderful children that we know in our hearts are truly miracles – special gifts from God.
Dr. Silber, I am not sure if you will ever know how much of an impact your work has on the people you serve. But I can tell you this, Gregg and I have not stopped smiling and thanking God since we found out that we were pregnant. You helped give us the best gifts we will ever receive – two children to love and call our own.
Please know that the work you do and the people you help will always be in our prayers. You are a remarkable doctor! Not a day goes by that we don't thank our lucky stars that our paths crossed and we were able to benefit from your tremendous knowledge.
We will continue to keep you updated on the progress of the Kaput twins. So far so good!
Sincerely,
Stephanie & Gregg Kaput
Plainfield, IL
In vitro fertilization (IVF) is a process by which egg cells are fertilised by sperm outside the body, in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed. The process involves hormonally controlling the ovulatory process, removing ova (eggs) from the woman's ovaries and letting sperm fertilise them in a fluid medium. For More Detailed Information : IVF matters
Tuesday, 17 May 2011
Patients Comments - 9
After 3 years of infertility we learned the results of my husband's genetic test for azoospermia and we were devastated. We were told that our chance of conceiving was 0%. The doctor recommended we put our money towards adoption or donor sperm. The test discovered that my husband has a very rare genetic anomaly. He is a Turner’s mosaic. This means that half of his cells are XO with no Y chromosome causing him to apparently make no sperm. We were in such disbelief that we decided to get a second opinion from the other reproductive group in town.
By this point it was late 2007 and we were beginning to think that children were just not in God’s plan for us. In January 2008 after watching an episode of “Private Practice” I was searching on the internet for information on testicular sperm extraction (TESE) and if it would work for Tracy’s anomaly. That is when I came across Dr. Silber’s name. After more searching on the internet I decided to order his book, “How to Get Pregnant.” His book gave my husband and I hope again. We decided that if anyone could make our dream of having a baby come true it was Dr. Silber and his team at the Infertility Center of St. Louis.
On February 4, 2008, we boarded a plane and went to meet Dr. Silber for a consult. He was intrigued by our case and certain he could help us achieve a pregnancy and have our miracle baby. With his expertise in infertility and his routine use of ICSI he gave us a good chance of finding sperm hiding in tiny numbers in the testicle. That to us was wonderful news. A year later we boarded another plane to St. Louis and began our 2 week period of monitoring and medication leading up to retrieval and implantation.
The office staff is wonderful. They are willing to help however necessary and are very knowledgeable. They called every night to let me know how much medicine to take and answer any questions.
My husband's testicular sperm extraction was successful and Dr. Silber was able to get enough sperm to fertilize all 13 eggs and even to freeze a few extra sperm for future use if necessary. Three days later I returned to St. Luke’s to have two embryos implanted. Two weeks after the implantation we received a phone call letting us know that we were finally pregnant. We both cried in elation! On October 26, 2009, after many years of hope and devastation our miracle was born. Without Dr. Silber and his wonderful team we might have given up on our dream of having a family.
Tracy, Heather and Brayden
Omaha, Nebraska
By this point it was late 2007 and we were beginning to think that children were just not in God’s plan for us. In January 2008 after watching an episode of “Private Practice” I was searching on the internet for information on testicular sperm extraction (TESE) and if it would work for Tracy’s anomaly. That is when I came across Dr. Silber’s name. After more searching on the internet I decided to order his book, “How to Get Pregnant.” His book gave my husband and I hope again. We decided that if anyone could make our dream of having a baby come true it was Dr. Silber and his team at the Infertility Center of St. Louis.
On February 4, 2008, we boarded a plane and went to meet Dr. Silber for a consult. He was intrigued by our case and certain he could help us achieve a pregnancy and have our miracle baby. With his expertise in infertility and his routine use of ICSI he gave us a good chance of finding sperm hiding in tiny numbers in the testicle. That to us was wonderful news. A year later we boarded another plane to St. Louis and began our 2 week period of monitoring and medication leading up to retrieval and implantation.
The office staff is wonderful. They are willing to help however necessary and are very knowledgeable. They called every night to let me know how much medicine to take and answer any questions.
My husband's testicular sperm extraction was successful and Dr. Silber was able to get enough sperm to fertilize all 13 eggs and even to freeze a few extra sperm for future use if necessary. Three days later I returned to St. Luke’s to have two embryos implanted. Two weeks after the implantation we received a phone call letting us know that we were finally pregnant. We both cried in elation! On October 26, 2009, after many years of hope and devastation our miracle was born. Without Dr. Silber and his wonderful team we might have given up on our dream of having a family.
Tracy, Heather and Brayden
Omaha, Nebraska
The History of IVF
1986
Monash IVF report on the world’s first pregnancy and birth from the sperm retrieval operation performed on a patient who had a blocked sperm duct.
First description of transvaginal sector scan sonography for needle-guided transvaginal follicle aspiration (Feichtinger W, Kemeter P. Transvaginal sector scan sonography for needle guided transvaginal follicle aspiration and other applications in gynecologic routine and research. Fertil Steril 1986 May;45(5):722-5).
First pregnancy, following IVF donated oocytes, in a non-ovarian failure patient. (Rosenwaks Z, Veeck LL, Liu HC.Pregnancy following transfer of in vitro fertilized donated oocytes. Fertil Steril. 1986;45(3):417-20).
First report on pregnancy after translaparoscopic zygote intrafallopian transfer (Devroey P, Braeckmans P, Smitz J, Van Waesberghe L, Wisanto A, Van Steirteghem A, Heytens L, Camu F. Pregnancy after translaparoscopic zygote intrafallopian transfer in a patient with sperm antibodies. Lancet, 1986 7;1:1329). In parallel the goup at the RWH was involved too in studies on gamete intra-Fallopian transfer (GIFT), (Molloy D, Speirs A, du Plessis Y, McBain J, Johnston I. A laparoscopic approach to a program of gamete intrafallopian transfer. Fertil Steril. 1987;47(2):289-94).
Delivery of twins from frozen human eggs (Chen C, Pregnancy after human oocyte cryopreservation. Lancet 1986, 1,884 – 886).
Christopher Chen
Jacqueline Mandelbaum with Dan Szollosi described the microstructures of the human oocyte, which becameknown as ‘oocyte dysmorphia’ (Szollosi D, Mandelbaum J, Plachot M, Salat-Baroux J, Cohen J. Ultrastructure of the human preovulatory oocyte. J In Vitro Fert Embryo Transf. 1986 ;3:232-42).
Monash IVF report on the world’s first pregnancy and birth from the sperm retrieval operation performed on a patient who had a blocked sperm duct.
First description of transvaginal sector scan sonography for needle-guided transvaginal follicle aspiration (Feichtinger W, Kemeter P. Transvaginal sector scan sonography for needle guided transvaginal follicle aspiration and other applications in gynecologic routine and research. Fertil Steril 1986 May;45(5):722-5).
First pregnancy, following IVF donated oocytes, in a non-ovarian failure patient. (Rosenwaks Z, Veeck LL, Liu HC.Pregnancy following transfer of in vitro fertilized donated oocytes. Fertil Steril. 1986;45(3):417-20).
First report on pregnancy after translaparoscopic zygote intrafallopian transfer (Devroey P, Braeckmans P, Smitz J, Van Waesberghe L, Wisanto A, Van Steirteghem A, Heytens L, Camu F. Pregnancy after translaparoscopic zygote intrafallopian transfer in a patient with sperm antibodies. Lancet, 1986 7;1:1329). In parallel the goup at the RWH was involved too in studies on gamete intra-Fallopian transfer (GIFT), (Molloy D, Speirs A, du Plessis Y, McBain J, Johnston I. A laparoscopic approach to a program of gamete intrafallopian transfer. Fertil Steril. 1987;47(2):289-94).
Delivery of twins from frozen human eggs (Chen C, Pregnancy after human oocyte cryopreservation. Lancet 1986, 1,884 – 886).
Christopher Chen
Jacqueline Mandelbaum with Dan Szollosi described the microstructures of the human oocyte, which becameknown as ‘oocyte dysmorphia’ (Szollosi D, Mandelbaum J, Plachot M, Salat-Baroux J, Cohen J. Ultrastructure of the human preovulatory oocyte. J In Vitro Fert Embryo Transf. 1986 ;3:232-42).
The History of IVF
1985
Human pregnancy by in vitro fertilization (IVF) using sperm aspirated from the epididymis. (Temple-Smith PD, Southwick GJ, Yates CA, Trounson AO, de Kretser DM. Human pregnancy by in vitro fertilization (IVF) using sperm aspirated from the epididymis. J In Vitro Fert Embryo Transf. 1985;2(3):119-22).
Epididymis sperm aspiration
Vaginal oocyte aspiration
Ultrasound image of follicles
GIFT procedure
Matts Wikland together with Lars Hamberger and
Lars Nilsson in Gothenburg, Sweden, described the possibility of using a vaginal sector scanner (transvaginal technique) for oocyte aspiration (Wikland M, Enk L, Hamberger L. Transvesical and transvaginal approaches for the aspiration of follicles by use of ultrasound. Ann N Y Acad Sci. 1985;442:182-94).
First report of the use of abdominal ultrasound guidance for embryo transfer. (Strickler RC, Christianson C, Crane JP, Curato A, Knight AB, Yang V. Ultrasound guidance for human embryo transfer. Fertil Steril 1985 ;43:54-61).
The first reported birth after replacement of hatching blastocyst cryopreserved at expanded blastocyst stage (Cohen J, Simons RF, Fehilly CB, Fishel SB, Edwards RG, Hewitt J, Rowlant GF, Steptoe PC, Webster JM. Birth after replacement of hatching blastocyst cryopreserved at expanded blastocyst stage. Lancet. 1985;16;1:647).
quinn
In 1985 Quinn and Warnes published a formula entitled Human Tubal Fluid (HTF) that mimics the in vivo environment to which the embryo is exposed (Quinn P, Kerin JF, Warnes GM. Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil Steril 1985;44:493-8).
First ultrasound guidance for human embryo transfer. (Strickler RC, Christianson C, Crane JP, Curato A, Knight AB, Yang V.Ultrasound guidance for human embryo transfer. Fertil Steril. 1985;43(1):54-61).
First Delivery Resulting From Gestational Surrogacy. (Utian WH, Sheean L, Goldfarb JM, Kiwi R. Successful pregnancy after in vitro fertilization and embryo transfer from an infertile woman to a surrogate. N Engl J Med. 1985:21;313(21):1351-2).
First successful egg donation in Europe. (Feichtinger W, Kemeter P. Pregnancy after total ovariectomy achieved by ovum donation. ancet. 1985:28;2(8457):722-3).
Transabdominal ultrsound guided embryo transfer (Strickler RC, Christianson C, Crane JP, Curato A, Knight AB, Yang V. Ultrasound guidance for human embryo transfer. Fertil Steril. 1985;43(1):54-61).
Navot et al. reported the possibility of artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries. (Navot D, Laufer N, Kopolovic J, Rabinowitz R, Birkenfeld A, Lewin A, Granat M, Margalioth EJ, Schenker JG.Artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries. N Engl J Med. 1986 Mar 27;314(13):806-11). Although it was published in 1986 it was first reported in 1985.
Human pregnancy by in vitro fertilization (IVF) using sperm aspirated from the epididymis. (Temple-Smith PD, Southwick GJ, Yates CA, Trounson AO, de Kretser DM. Human pregnancy by in vitro fertilization (IVF) using sperm aspirated from the epididymis. J In Vitro Fert Embryo Transf. 1985;2(3):119-22).
Epididymis sperm aspiration
Vaginal oocyte aspiration
Ultrasound image of follicles
GIFT procedure
Matts Wikland together with Lars Hamberger and
Lars Nilsson in Gothenburg, Sweden, described the possibility of using a vaginal sector scanner (transvaginal technique) for oocyte aspiration (Wikland M, Enk L, Hamberger L. Transvesical and transvaginal approaches for the aspiration of follicles by use of ultrasound. Ann N Y Acad Sci. 1985;442:182-94).
First report of the use of abdominal ultrasound guidance for embryo transfer. (Strickler RC, Christianson C, Crane JP, Curato A, Knight AB, Yang V. Ultrasound guidance for human embryo transfer. Fertil Steril 1985 ;43:54-61).
The first reported birth after replacement of hatching blastocyst cryopreserved at expanded blastocyst stage (Cohen J, Simons RF, Fehilly CB, Fishel SB, Edwards RG, Hewitt J, Rowlant GF, Steptoe PC, Webster JM. Birth after replacement of hatching blastocyst cryopreserved at expanded blastocyst stage. Lancet. 1985;16;1:647).
quinn
In 1985 Quinn and Warnes published a formula entitled Human Tubal Fluid (HTF) that mimics the in vivo environment to which the embryo is exposed (Quinn P, Kerin JF, Warnes GM. Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil Steril 1985;44:493-8).
First ultrasound guidance for human embryo transfer. (Strickler RC, Christianson C, Crane JP, Curato A, Knight AB, Yang V.Ultrasound guidance for human embryo transfer. Fertil Steril. 1985;43(1):54-61).
First Delivery Resulting From Gestational Surrogacy. (Utian WH, Sheean L, Goldfarb JM, Kiwi R. Successful pregnancy after in vitro fertilization and embryo transfer from an infertile woman to a surrogate. N Engl J Med. 1985:21;313(21):1351-2).
First successful egg donation in Europe. (Feichtinger W, Kemeter P. Pregnancy after total ovariectomy achieved by ovum donation. ancet. 1985:28;2(8457):722-3).
Transabdominal ultrsound guided embryo transfer (Strickler RC, Christianson C, Crane JP, Curato A, Knight AB, Yang V. Ultrasound guidance for human embryo transfer. Fertil Steril. 1985;43(1):54-61).
Navot et al. reported the possibility of artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries. (Navot D, Laufer N, Kopolovic J, Rabinowitz R, Birkenfeld A, Lewin A, Granat M, Margalioth EJ, Schenker JG.Artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries. N Engl J Med. 1986 Mar 27;314(13):806-11). Although it was published in 1986 it was first reported in 1985.
The History of IVF
The Government of Victoria established a review of IVF research and practice which led to the proclamation of the Infertility (Medical Procedures) Act 1984, the first legislation to regulate IVF and its associated human embryo research.
First surrogacy embryo transfer baby born in California
First report on pregnancy following translaparoscopic GIFT procedure (Asch RH, Ellsworth LR, Balmaceda JP, Wong PC. Pregnancy after translaparoscopic gamete intrafallopian transfer. Lancet, 1984;3;2:1034-5).
The first report on pregnancy following IVF and egg donation in a woman with primary ovarian failure. (Lutjen P, Trounson A, Leeton J, Findlay J, Wood C and Renou P. The establishment and maintenance of pregnancy using in vitro fertilization and embryo donation in a patient with primary ovarian failure. Nature, 1984;307,174 – 175).
Introduction of GnRH agonists to the IVF treatment protocol (Porter RN, Smith W, Craft IL, Abdulwahid NA, Jacobs HS. Induction of ovulation for in-vitro fertilisation using buserelin and gonadotropins. Lancet, 1984;1;2:1284-5).
A report of pregnancy following transfer of intact frozen-thawed embryos (Zeilmaker GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC.Two pregnancies following transfer of intact frozen-thawed embryos. Fertil Steril. 1984;42(2):293-6).
An unusual report of the possibility that abnormal spermatozoa could be enriched and give rise to healthy babies. (Cohen J, Fehilly CB, Fishel SB, Edwards RG, Hewitt J, Rowland GF, Steptoe PC, Webster J. Male infertility successfully treated by in-vitro fertilisation.Lancet. 1984, 2;1(8388):1239-40).
The first publication demonstrating HCG secretion by the human embryo (Fishel SB, Edwards RG, Evans CJ. Human chorionic gonadotropin secreted by preimplantation embryos cultured in vitro.Science. 1984, 24;223(4638):816-8).
The world's first IVF quadruplets were born on January 6, 1984, in Melbourne.
First surrogacy embryo transfer baby born in California
First report on pregnancy following translaparoscopic GIFT procedure (Asch RH, Ellsworth LR, Balmaceda JP, Wong PC. Pregnancy after translaparoscopic gamete intrafallopian transfer. Lancet, 1984;3;2:1034-5).
The first report on pregnancy following IVF and egg donation in a woman with primary ovarian failure. (Lutjen P, Trounson A, Leeton J, Findlay J, Wood C and Renou P. The establishment and maintenance of pregnancy using in vitro fertilization and embryo donation in a patient with primary ovarian failure. Nature, 1984;307,174 – 175).
Introduction of GnRH agonists to the IVF treatment protocol (Porter RN, Smith W, Craft IL, Abdulwahid NA, Jacobs HS. Induction of ovulation for in-vitro fertilisation using buserelin and gonadotropins. Lancet, 1984;1;2:1284-5).
A report of pregnancy following transfer of intact frozen-thawed embryos (Zeilmaker GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC.Two pregnancies following transfer of intact frozen-thawed embryos. Fertil Steril. 1984;42(2):293-6).
An unusual report of the possibility that abnormal spermatozoa could be enriched and give rise to healthy babies. (Cohen J, Fehilly CB, Fishel SB, Edwards RG, Hewitt J, Rowland GF, Steptoe PC, Webster J. Male infertility successfully treated by in-vitro fertilisation.Lancet. 1984, 2;1(8388):1239-40).
The first publication demonstrating HCG secretion by the human embryo (Fishel SB, Edwards RG, Evans CJ. Human chorionic gonadotropin secreted by preimplantation embryos cultured in vitro.Science. 1984, 24;223(4638):816-8).
The world's first IVF quadruplets were born on January 6, 1984, in Melbourne.
Monday, 16 May 2011
Patients Comments - 8
Dr. Silber,
I want to start by saying that Dr. Silber and all his staff are Amazing! My husband and I knew since the moment we met we wanted children. So after we were married for a year we started talking about starting our family. We figure maybe a month later we would be pregnant then nine months later we would have our baby and live happily ever after. Well after about 5 months we started to get worried and started having tests done to find the problem but we were only looking at me. After a year Robbie decided to get checked and we found out that he was born with a blockage of the vas deferens. A friend of mine told me about Dr. Silber, so I decided that we would go talk to him and get more information. I was scared to talk to Dr. Silber, because I was afraid that he was going to tell us that we would never have children.
Dr. Silber made us feel so comfortable, he listened to our feelings and never once lead us to believe that he could do something that he couldn't. Dr. Silber was very honest with us and reassured us that IVF would be the only way we would get pregnant. We loved that we never felt pressured into anything; we were given the facts and all the information and left to decide what we wanted.
Thanks to Dr. Silber and his staff we have beautiful 20 month old twins.
Thanks,
Robbie, Shanna, Cauy & Skylee Mondy
Old Monroe, MO
I want to start by saying that Dr. Silber and all his staff are Amazing! My husband and I knew since the moment we met we wanted children. So after we were married for a year we started talking about starting our family. We figure maybe a month later we would be pregnant then nine months later we would have our baby and live happily ever after. Well after about 5 months we started to get worried and started having tests done to find the problem but we were only looking at me. After a year Robbie decided to get checked and we found out that he was born with a blockage of the vas deferens. A friend of mine told me about Dr. Silber, so I decided that we would go talk to him and get more information. I was scared to talk to Dr. Silber, because I was afraid that he was going to tell us that we would never have children.
Dr. Silber made us feel so comfortable, he listened to our feelings and never once lead us to believe that he could do something that he couldn't. Dr. Silber was very honest with us and reassured us that IVF would be the only way we would get pregnant. We loved that we never felt pressured into anything; we were given the facts and all the information and left to decide what we wanted.
Thanks to Dr. Silber and his staff we have beautiful 20 month old twins.
Thanks,
Robbie, Shanna, Cauy & Skylee Mondy
Old Monroe, MO
Pateints Comment - 7
My Story,
I am a leukemia survivor and blood stem cell transplant recipient. After treatment left me infertile, I heard about Dr. Silber and the ovarian transplants he was doing. It sounded like science fiction, but it wasn’t!
I was so lucky to have an identical twin sister. We were adopted from Korea when we were 14 months old. We thought that we were fortunate to have been adopted together—little did we know how fortunate it was! Rachel was able to donate the blood stem cells as well as the ovary. Dr. Silber did the surgery.
I began to ovulate about 3-4 months after the transplant! It was truly amazing. The road to pregnancy was still not straightforward. I had two miscarriages which were heartbreaking and so when I got pregnant for the third time, it was difficult to believe it would actually work. But after the first ultrasound that showed a strong heartbeat, and the second that showed the fetus developing normally, we started to believe it was real.
I gave birth to my son, Miles, in November 2009. He is so precious. Both my husband and I are ecstatic. Dr. Silber provides new hope to women who once thought they would never be able to give birth.
If you can dream it, Google it, and maybe you’ll find a Dr. Silber on the other end!
Nate, Anna, and Miles Heard
Washington, DC
and
Rachel Cederberg
Colorado Springs, CO
I am a leukemia survivor and blood stem cell transplant recipient. After treatment left me infertile, I heard about Dr. Silber and the ovarian transplants he was doing. It sounded like science fiction, but it wasn’t!
I was so lucky to have an identical twin sister. We were adopted from Korea when we were 14 months old. We thought that we were fortunate to have been adopted together—little did we know how fortunate it was! Rachel was able to donate the blood stem cells as well as the ovary. Dr. Silber did the surgery.
I began to ovulate about 3-4 months after the transplant! It was truly amazing. The road to pregnancy was still not straightforward. I had two miscarriages which were heartbreaking and so when I got pregnant for the third time, it was difficult to believe it would actually work. But after the first ultrasound that showed a strong heartbeat, and the second that showed the fetus developing normally, we started to believe it was real.
I gave birth to my son, Miles, in November 2009. He is so precious. Both my husband and I are ecstatic. Dr. Silber provides new hope to women who once thought they would never be able to give birth.
If you can dream it, Google it, and maybe you’ll find a Dr. Silber on the other end!
Nate, Anna, and Miles Heard
Washington, DC
and
Rachel Cederberg
Colorado Springs, CO
The History of IVF
1982
The first French IVF birth occurred in Clamart, France by the group of Frydman and Testart.
The first IVF birth in Sweden (Hamberger L, Wikland M, Nilsson L, Janson PO, Sjo¨ gren A and Hillensjo¨ T (1982) Methods for aspiration of human oocytes by various techniques. Acta Med Rom 20,370 – 378).
Birth of first Austrian "Test tube baby" (Twin pregnancy) (Feichtinger W, Szalay S, Kemeter P, Beck A, Janisch H.Twin pregnancy after laparoscopic oocyte recovery, in-vitro fertilization and embryotransfer (author's transl)]Geburtshilfe Frauenheilkd. 1982;42(3):197-9).
Richard Fleming
The first demonstration that GnRH agonists can be used to eliminate premature luteinization and control ovarian stimulation (Fleming R, Adam AH, Barlow DH, Black WP, MacNaughton MC, Coutts JR. A new systematic treatment for infertile women with abnormal hormone profiles. Br J Obstet Gynaecol. 1982 ;89:80-3).
The first report of the need for a delay between oocyte collection and insemination to allow oocytes collected to complete maturation (Trounson AO, Mohr LR, Wood C, Leeton JF. Effect of delayed insemination on in-vitro fertilization, culture and transfer of human embryos. J Reprod Fertil 1982;64:285-94).
Susan Lenz
Susan Lenz and Jurgen G Lauritsen demonstrated trans abdominal transvesical oocyte aspiration using an ultrasound-guided needle (Lenz S, Lauritsen JG. Ultrasonically guided percutaneous aspiration of human follicles under local anesthesia: a new method of collecting oocytes for in vitro fertilization. Fertil Steril 1982;38:673-7).
Ian Craft in London reported a pregnancy from transfer of gametes to the uterus (Craft I, Djahanbakhch O, McLeod F, Bernard A, Green S, Twigg H, Smith W, Lindsay K, Edmonds K. Human pregnancy following oocyte and sperm transfer to the uterus.Lancet. 1982, 8;1(8280):1031-3).
The first French IVF birth occurred in Clamart, France by the group of Frydman and Testart.
The first IVF birth in Sweden (Hamberger L, Wikland M, Nilsson L, Janson PO, Sjo¨ gren A and Hillensjo¨ T (1982) Methods for aspiration of human oocytes by various techniques. Acta Med Rom 20,370 – 378).
Birth of first Austrian "Test tube baby" (Twin pregnancy) (Feichtinger W, Szalay S, Kemeter P, Beck A, Janisch H.Twin pregnancy after laparoscopic oocyte recovery, in-vitro fertilization and embryotransfer (author's transl)]Geburtshilfe Frauenheilkd. 1982;42(3):197-9).
Richard Fleming
The first demonstration that GnRH agonists can be used to eliminate premature luteinization and control ovarian stimulation (Fleming R, Adam AH, Barlow DH, Black WP, MacNaughton MC, Coutts JR. A new systematic treatment for infertile women with abnormal hormone profiles. Br J Obstet Gynaecol. 1982 ;89:80-3).
The first report of the need for a delay between oocyte collection and insemination to allow oocytes collected to complete maturation (Trounson AO, Mohr LR, Wood C, Leeton JF. Effect of delayed insemination on in-vitro fertilization, culture and transfer of human embryos. J Reprod Fertil 1982;64:285-94).
Susan Lenz
Susan Lenz and Jurgen G Lauritsen demonstrated trans abdominal transvesical oocyte aspiration using an ultrasound-guided needle (Lenz S, Lauritsen JG. Ultrasonically guided percutaneous aspiration of human follicles under local anesthesia: a new method of collecting oocytes for in vitro fertilization. Fertil Steril 1982;38:673-7).
Ian Craft in London reported a pregnancy from transfer of gametes to the uterus (Craft I, Djahanbakhch O, McLeod F, Bernard A, Green S, Twigg H, Smith W, Lindsay K, Edmonds K. Human pregnancy following oocyte and sperm transfer to the uterus.Lancet. 1982, 8;1(8280):1031-3).
The History of IVF
1981
Howard and Georgianna Seegar Jones announced the delivery of the first IVF baby in the United States. This first IVF birth in the USA was achieved with the use of hMG.
Wood and his colleague introduced a foot-controlled fixed aspiration pressure control (Wood C, Leeton J, Talbot JM, Trounson AO. Technique for collecting mature human oocytes for in vitro fertilization. Br J Obstet Gynaecol. 1981;88(7):756-60).
Introduction of Clomiphene Citrate and hMG in the IVF treatment protocol (Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies in humans by fertilization in vitro and embryo transfer in the controlled ovulatory cycle. Science 1981 8;212:681-2) .
The Clamart group in France developed an LH assay (LH-SIR0 which could detect the initial LH rise in plasma allowing accurate prediction of the ideal time for the retrieval of oocytes (Testart J, Frydman R, Feinstein MC, Thebault A, Roger M, Scholler R. Interpretation of plasma luteinizing hormone assay for the collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise. Fertil Steril. 1981 Jul;36(1):50-4).
Howard and Georgianna Seegar Jones announced the delivery of the first IVF baby in the United States. This first IVF birth in the USA was achieved with the use of hMG.
Wood and his colleague introduced a foot-controlled fixed aspiration pressure control (Wood C, Leeton J, Talbot JM, Trounson AO. Technique for collecting mature human oocytes for in vitro fertilization. Br J Obstet Gynaecol. 1981;88(7):756-60).
Introduction of Clomiphene Citrate and hMG in the IVF treatment protocol (Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies in humans by fertilization in vitro and embryo transfer in the controlled ovulatory cycle. Science 1981 8;212:681-2) .
The Clamart group in France developed an LH assay (LH-SIR0 which could detect the initial LH rise in plasma allowing accurate prediction of the ideal time for the retrieval of oocytes (Testart J, Frydman R, Feinstein MC, Thebault A, Roger M, Scholler R. Interpretation of plasma luteinizing hormone assay for the collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise. Fertil Steril. 1981 Jul;36(1):50-4).
The History of IVF -The Milestones
1979
Pez et al, began tracking the growth of follicles by ultrasound. They showed an appreciable relationship between the echographic and laparoscopic observations (Pez JP, Cohen J et al. 1979 Recherche d’une concordance entre l’e´chographie et l’observation par coelioscopie des follicules stimule´s par les inducteurs de l’ovulation. 178 soire´e gyne´co-obstricale de St Maurice le 9.10.79. Milupa. Bagnolet).
The first published use of ultrasound to identify growing follicles (Hackeloer BJ, 1977, The ultrasonic demonstration of follicular development during the normal menstrual cycle and after hormone stimulation. In Kurjak A (ed) Recent Advances in Ultrasound Diagnosis. Excerpta Medica, Amsterdam-Oxford, pp 122 – 128).
Pez et al, began tracking the growth of follicles by ultrasound. They showed an appreciable relationship between the echographic and laparoscopic observations (Pez JP, Cohen J et al. 1979 Recherche d’une concordance entre l’e´chographie et l’observation par coelioscopie des follicules stimule´s par les inducteurs de l’ovulation. 178 soire´e gyne´co-obstricale de St Maurice le 9.10.79. Milupa. Bagnolet).
The first published use of ultrasound to identify growing follicles (Hackeloer BJ, 1977, The ultrasonic demonstration of follicular development during the normal menstrual cycle and after hormone stimulation. In Kurjak A (ed) Recent Advances in Ultrasound Diagnosis. Excerpta Medica, Amsterdam-Oxford, pp 122 – 128).
Friday, 13 May 2011
Patient Comment - 6
I wanted to write and thank you for making Mother’s Day 2010 one of the best days of my life. We celebrated with our amazing two-month-old twin baby girls and we wanted to extend our sincerest gratitude for helping us realize our dream to become parents.
We were both well over 40 and every doctor told us there was NO CHANCE. We soon found that local doctors were not willing to ‘work with us’ because of my age (42 at the time we first sought help). We changed doctors 3 times and they all prescribed the same conventional treatments and tests. This went on for a whole year while I was just getting even older. We finally figured out these doctors were trying to waste enough time to force us into using donor eggs, rather than pursue a plan that would help us try to have our OWN children. We realized that using donor eggs is a viable option for some couples but had told each doctor from the beginning that was not what we wanted. I was devastated when I realized they had basically wasted 11 precious months of our time!
Then we saw Dr. Silber. I figured if Dr. Silber was that good at thinking outside of the box, he could help a healthy 43 year old become a mother. I ‘googled’ and found out the office was only a four and a half hour drive away.
We believe that God works through people and we had a feeling we were in the right place when we noticed a ‘promise’ displayed on the wall that said Dr. Silber would work to the best of the ability God had given him to help people. Dr. Silber explained to us the odds of conceiving because of my age, now 43, but he also had a plan to give us a chance. Things seemed to keep telling us we were on the right track.
July 6th we found out we were pregnant. July 21st we found out it was twins! WOW!! I was treated like any other ‘normal’ high-risk pregnancy because of my ‘advanced maternal age’ of 43 and carrying twins. I had a very healthy pregnancy and made it to 39 weeks with what my OB described as a pregnancy better than most of her moms carrying ‘singletons’. We had beaten the odds.
Our very healthy and alert baby girls were born one week after my 44th birthday on March 8th! They continue to amaze us each day as we watch them grow and change. Brielle and Lillian bring such joy to our lives and we have not stopped smiling. We are so blessed.
We cannot thank you enough for your willingness to extend your expertise to successfully treat the infertility issues which older couples face.
Forever Grateful,
Dan & Lorelei Andedo
Rock Island, Illinois
We were both well over 40 and every doctor told us there was NO CHANCE. We soon found that local doctors were not willing to ‘work with us’ because of my age (42 at the time we first sought help). We changed doctors 3 times and they all prescribed the same conventional treatments and tests. This went on for a whole year while I was just getting even older. We finally figured out these doctors were trying to waste enough time to force us into using donor eggs, rather than pursue a plan that would help us try to have our OWN children. We realized that using donor eggs is a viable option for some couples but had told each doctor from the beginning that was not what we wanted. I was devastated when I realized they had basically wasted 11 precious months of our time!
Then we saw Dr. Silber. I figured if Dr. Silber was that good at thinking outside of the box, he could help a healthy 43 year old become a mother. I ‘googled’ and found out the office was only a four and a half hour drive away.
We believe that God works through people and we had a feeling we were in the right place when we noticed a ‘promise’ displayed on the wall that said Dr. Silber would work to the best of the ability God had given him to help people. Dr. Silber explained to us the odds of conceiving because of my age, now 43, but he also had a plan to give us a chance. Things seemed to keep telling us we were on the right track.
July 6th we found out we were pregnant. July 21st we found out it was twins! WOW!! I was treated like any other ‘normal’ high-risk pregnancy because of my ‘advanced maternal age’ of 43 and carrying twins. I had a very healthy pregnancy and made it to 39 weeks with what my OB described as a pregnancy better than most of her moms carrying ‘singletons’. We had beaten the odds.
Our very healthy and alert baby girls were born one week after my 44th birthday on March 8th! They continue to amaze us each day as we watch them grow and change. Brielle and Lillian bring such joy to our lives and we have not stopped smiling. We are so blessed.
We cannot thank you enough for your willingness to extend your expertise to successfully treat the infertility issues which older couples face.
Forever Grateful,
Dan & Lorelei Andedo
Rock Island, Illinois
Patient Comment - 5
In 2003 we were a typical military family of four. With our daughters ages 11 and 5 we felt extremely blessed and for the most part, fulfilled. After 11 yrs in the military we decided it was time to move on to the civilian world. So with logic over shadowing the deep hidden desire for a bigger family we went ahead and had a vasectomy. The gloom of making such a big mistake and not ever being able to have more children really put a black cloud over her head.
Then one evening we caught a special on television about a gifted doctor performing special miracles for people like us. It gave us hope. So we contacted Dr Silber's office after a couple weeks of debating the pros and cons for a vasectomy reversal, after all we didn't want to make another HUGE mistake.
So in the early summer of 2006 Dr Silber performed his magic. We stopped trying so hard and decided to let things take their natural course. Within a month we were pregnant again!! On September 27th, 2008 my wife gave birth to a very healthy baby boy. Tanner was 7lbs 12oz and 21inches long and ready to take over the house. Our house finally had a happy atmosphere again, my wife felt fulfilled, we had a son to pass on the name, things couldn't be more perfect.
Then at the beginning of 2009, to our surprise, we were pregnant again. Then a few weeks later another surprise, TWINS!!! Then a few months later another surprise IDENTICAL GIRLS!!!! We wanted a big family and we got it. On 28 October 2009 our twin girls Jessica and Gracie Lynn were born at 5lbs 5oz each and 19 inches long. Now we are beyond fulfilled and are comfortable with saying our family is big enough.
Thank you Dr Silber and all your team members for giving us the chance to become ONE BIG HAPPY FAMILY!!
Branden, Angel, Danielle (17), Kailey (11), Tanner (14mths), Jessica (1mth), and Gracie Lynn (1mth)
Cedar Hill, MO
Then one evening we caught a special on television about a gifted doctor performing special miracles for people like us. It gave us hope. So we contacted Dr Silber's office after a couple weeks of debating the pros and cons for a vasectomy reversal, after all we didn't want to make another HUGE mistake.
So in the early summer of 2006 Dr Silber performed his magic. We stopped trying so hard and decided to let things take their natural course. Within a month we were pregnant again!! On September 27th, 2008 my wife gave birth to a very healthy baby boy. Tanner was 7lbs 12oz and 21inches long and ready to take over the house. Our house finally had a happy atmosphere again, my wife felt fulfilled, we had a son to pass on the name, things couldn't be more perfect.
Then at the beginning of 2009, to our surprise, we were pregnant again. Then a few weeks later another surprise, TWINS!!! Then a few months later another surprise IDENTICAL GIRLS!!!! We wanted a big family and we got it. On 28 October 2009 our twin girls Jessica and Gracie Lynn were born at 5lbs 5oz each and 19 inches long. Now we are beyond fulfilled and are comfortable with saying our family is big enough.
Thank you Dr Silber and all your team members for giving us the chance to become ONE BIG HAPPY FAMILY!!
Branden, Angel, Danielle (17), Kailey (11), Tanner (14mths), Jessica (1mth), and Gracie Lynn (1mth)
Cedar Hill, MO
Front page of the Sunday New York Times agrees with Dr. Silber on octuplets issue
It was the last piece of advice Thomas and Amanda Stansel wanted to hear. But their fertility doctor was delivering it, without sugarcoating.
Reduce, or you will lose them all, he told them.
For more than a year the Stansels had been relying on Dr. George Grunert, one of the busiest fertility doctors in Houston, to produce his industry’s coveted product — a healthy baby. He was using a common procedure called intrauterine insemination, which involved injecting sperm into Mrs. Stansel’s uterus after hormone shots.
But something had gone wrong. In April, an ultrasound revealed that Mrs. Stansel was carrying not one but six babies, and Dr. Grunert was recommending a procedure known as selective reduction, in which some of the fetuses would be eliminated.
The Stansels rejected Dr. Grunert’s advice and, since then, their vision of a family has collapsed into excruciating loss: the deaths of four children after their premature births on Aug. 4, including one who died late Sunday night. The two other infants remain in neonatal intensive care, their futures uncertain.
“I feel like we bonded with all of them, the short time they were here,” Mr. Stansel said. “We were able to hold them before they passed away.”
The birth of octuplets in California in January placed the onus for large multiple births on in vitro fertilization, a treatment in which eggs are joined with sperm in a petri dish and returned to the womb for gestation.
But the procedure the Stansels used is actually the major cause of quadruplets, quintuplets and sextuplets — the most dangerous pregnancies for both mother and children. While less effective than IVF, intrauterine insemination is used at least twice as frequently because it is less invasive, cheaper and more likely to be covered by insurance, interviews and data show.
Multiples can occur when the high-potency hormones frequently used with the procedure overstimulate the ovaries and produce large numbers of eggs. Parents are then left with the kind of tough choices the Stansels faced: whether to eliminate some of the fetuses or keep the babies and face extraordinary risks.
Reduce, or you will lose them all, he told them.
For more than a year the Stansels had been relying on Dr. George Grunert, one of the busiest fertility doctors in Houston, to produce his industry’s coveted product — a healthy baby. He was using a common procedure called intrauterine insemination, which involved injecting sperm into Mrs. Stansel’s uterus after hormone shots.
But something had gone wrong. In April, an ultrasound revealed that Mrs. Stansel was carrying not one but six babies, and Dr. Grunert was recommending a procedure known as selective reduction, in which some of the fetuses would be eliminated.
The Stansels rejected Dr. Grunert’s advice and, since then, their vision of a family has collapsed into excruciating loss: the deaths of four children after their premature births on Aug. 4, including one who died late Sunday night. The two other infants remain in neonatal intensive care, their futures uncertain.
“I feel like we bonded with all of them, the short time they were here,” Mr. Stansel said. “We were able to hold them before they passed away.”
The birth of octuplets in California in January placed the onus for large multiple births on in vitro fertilization, a treatment in which eggs are joined with sperm in a petri dish and returned to the womb for gestation.
But the procedure the Stansels used is actually the major cause of quadruplets, quintuplets and sextuplets — the most dangerous pregnancies for both mother and children. While less effective than IVF, intrauterine insemination is used at least twice as frequently because it is less invasive, cheaper and more likely to be covered by insurance, interviews and data show.
Multiples can occur when the high-potency hormones frequently used with the procedure overstimulate the ovaries and produce large numbers of eggs. Parents are then left with the kind of tough choices the Stansels faced: whether to eliminate some of the fetuses or keep the babies and face extraordinary risks.
Microsurgical vasectomy reversal is not just vasovasostomy
Vasectomy reversal is often incorrectly thought of as simply a reconnection of the severed vas deferens. In fact, the term many doctors mistakenly use for the reversal of vasectomy is “vasovasostomy”. But vasovasostomy just means reconnecting the vas. Simply “reconnecting the vas” is not enough to restore fertility to most vasectomized men. The reason for so many failures of vasectomy reversal, even with “microsurgery”, is that in over 80 per cent of cases the pressure buildup inside the vas (caused by the original vasectomy) results in microscopic “blowouts” and “concretions” in the more delicate ductwork closer to the testicle (called the “epididymis”) which is where the sperm leave the testis on their way to the vas. If this complex, truly more delicate pathway, the epididymis, is not microscopically bypassed, the vasovasostomy will not work, because the sperm still cannot get to the site of the vas reconnection. They are blocked from even reaching the vasovasostomy site because the more delicate ductwork closer to the testicle remains blocked. So the routinely performed vasovasostomy was destined never to work no matter how accurate the reconnection.
The reason for this most commonly practiced error is that repair of the epididymis is very difficult, and requires years of very specialized practice and experience. Most urologists would be lost in the epididymis. So they might very earnestly apply what they think are “microsurgical skills” to perform a vasovasostomy, just hoping that there are no proximal blowouts in the epididymis. They might even tell the patient that they saw “sperm” in the vas fluid at the time of the vasovasostomy, increasing their hope that vasovasostomy is enough in their case. They will do anything to avoid trying to repair the usually obstructed epididymis because it is so difficult for the less experienced.
The problem is that there will always be creamy thick fluid in the vas deference on the proximal side of the vasectomy site, which has been stored in that obstructed site for years, and there might even be decayed old dead sperm or sperm parts in that fluid, and so it might be mistaken for epididymal continuity. But if the vas does not have translucent fluid with normal intact motile sperm, then you can be sure that no fresh new sperm have reached this area for many years, because of epididymal blockage more proximally. So you might leave the clinic with “wait and see” advice from the doctor even though there is no chance of the “vasovasostomy” working. It may not be until a year later with consistently negative semen analysis results, that you realize you had the wrong operation.
This problem of epididymal blowouts is much more common now than 20 or 30 years ago, and occurs much earlier after vasectomy, as early as 6 months even. The reason is that urologists are performing the original vasectomy much more tightly, allowing no leaks whatsoever of sperm. Therefore, it is important for the microsurgeon to perform this more delicate vasoepididymostomy procedure in over 80 per cent of cases, when there is secondary epididymal blockage.
The reason for this most commonly practiced error is that repair of the epididymis is very difficult, and requires years of very specialized practice and experience. Most urologists would be lost in the epididymis. So they might very earnestly apply what they think are “microsurgical skills” to perform a vasovasostomy, just hoping that there are no proximal blowouts in the epididymis. They might even tell the patient that they saw “sperm” in the vas fluid at the time of the vasovasostomy, increasing their hope that vasovasostomy is enough in their case. They will do anything to avoid trying to repair the usually obstructed epididymis because it is so difficult for the less experienced.
The problem is that there will always be creamy thick fluid in the vas deference on the proximal side of the vasectomy site, which has been stored in that obstructed site for years, and there might even be decayed old dead sperm or sperm parts in that fluid, and so it might be mistaken for epididymal continuity. But if the vas does not have translucent fluid with normal intact motile sperm, then you can be sure that no fresh new sperm have reached this area for many years, because of epididymal blockage more proximally. So you might leave the clinic with “wait and see” advice from the doctor even though there is no chance of the “vasovasostomy” working. It may not be until a year later with consistently negative semen analysis results, that you realize you had the wrong operation.
This problem of epididymal blowouts is much more common now than 20 or 30 years ago, and occurs much earlier after vasectomy, as early as 6 months even. The reason is that urologists are performing the original vasectomy much more tightly, allowing no leaks whatsoever of sperm. Therefore, it is important for the microsurgeon to perform this more delicate vasoepididymostomy procedure in over 80 per cent of cases, when there is secondary epididymal blockage.
After 25 Years of IVF, Couple Finally Conceives
After more than 20 years and nearly $200,000 worth of failed infertility treatments, Monique and Neil Ward of Stafford, England, have finally became the proud parents of twin boys, Britain's Press Association reports.
The Wards' 25-year struggle to become pregnant -- even though ultimately it was through the use of donor sperm and donor eggs -- raises a question many infertility specialists and aspiring parents face: Does there come a point when a couple should give up on trying to conceive?
After 15 failed attempts with various types of assisted reproductive technology since 1986, some might say the Wards were operating on blind optimism when they signed up for another $20,000 round of in vitro fertilization (IVF) with donor eggs and sperm last spring. An earlier round with this technique had failed five months before.
But against all odds, Monique Ward finally became pregnant. On Dec. 29, at the age of 46, she gave birth to two healthy twin boys, Walker and Benjamin.
The Wards' 25-year struggle to become pregnant -- even though ultimately it was through the use of donor sperm and donor eggs -- raises a question many infertility specialists and aspiring parents face: Does there come a point when a couple should give up on trying to conceive?
After 15 failed attempts with various types of assisted reproductive technology since 1986, some might say the Wards were operating on blind optimism when they signed up for another $20,000 round of in vitro fertilization (IVF) with donor eggs and sperm last spring. An earlier round with this technique had failed five months before.
But against all odds, Monique Ward finally became pregnant. On Dec. 29, at the age of 46, she gave birth to two healthy twin boys, Walker and Benjamin.
Vasectomy Reversal Pitfalls?
nfortunately, there are many patients who receive poor microsurgical care by physicians who do not have the proper expertise and who commercialize vasectomy reversal for easy profit. So there are many traps to watch out for when choosing a doctor to perform your reversal.
For example, some doctors will offer a “money back guarantee,” but patients rarely get their money back after a failed procedure despite promises to the contrary. We have operated on many patients whose previous vasectomy reversal attempts at “money back guarantee centers” had failed, and none of these patients have ever gotten their money back. There was always some fine print wording that allowed the clinic to keep their money despite the “money back guarantee.”
In most so-called “centers,” the only procedure performed to reverse the vasectomy is “vasovasostomy” to try to reconnect the severed vas. However, in most cases there is also “epididymal” blockage (closer to the testicles) created by the pressure build-up after vasectomy. Thus, there is no chance for most cases of “vasovasostomy” to be a success, because there is also blockage in the more delicate duct closer to the testis, and this would have to be bypassed also with a very tricky-to-perform “vasoepididymostomy” in order to have a successful result.
For example, some doctors will offer a “money back guarantee,” but patients rarely get their money back after a failed procedure despite promises to the contrary. We have operated on many patients whose previous vasectomy reversal attempts at “money back guarantee centers” had failed, and none of these patients have ever gotten their money back. There was always some fine print wording that allowed the clinic to keep their money despite the “money back guarantee.”
In most so-called “centers,” the only procedure performed to reverse the vasectomy is “vasovasostomy” to try to reconnect the severed vas. However, in most cases there is also “epididymal” blockage (closer to the testicles) created by the pressure build-up after vasectomy. Thus, there is no chance for most cases of “vasovasostomy” to be a success, because there is also blockage in the more delicate duct closer to the testis, and this would have to be bypassed also with a very tricky-to-perform “vasoepididymostomy” in order to have a successful result.
Wednesday, 11 May 2011
What makes the Y chromosome, with its confounding repeats, polymorphisms, and degenerating regions, such an interesting study object for male infertility?
The answer lies in the evolutionary history of the X and Y chromosomes. Over the course of the past 240-320 million years of mammalian evolution, the X and Y chromosomes have evolved from what was originally a pair of ordinary autosomes (Figure 5). During that evolution, just as most of the ancestral X genes were decaying on the Y because of the lack of meiotic recombination, genes which control spermatogenesis arrived on the Y from autosomes. Once on the Y, these formerly autosomal genes amplified into multiple copies, and achieved greater prominence through a process called “gene conversion.” Spermatogenesis genes that arrived on the Y, but came originally from autosomes, include the DAZ (from autosome 3) and CDY (from autosome 6) genes that are among the seven gene families located in AZFc (Figure 6). Other spermatogenesis genes on the Y, such as RBMY, have persisted in their original position as on the X. The ancestral gene that remained on the X chromosome (RBMX) retained its widespread cellular functions, whereas RBMY, which persisted on the receding Y chromosome, evolved a male-specific function in spermatogenesis. Male benefit genes have thus arrived and accumulated on the evolving Y chromosome over many millions of years.
This evolution of the modern X and Y chromosomes was initiated by the emergence of a male sex-determining gene (now known as SRY) on what was originally an ordinary pair of autosomes (Figure 5). Genes associated with the non-recombining SRY region that were specifically beneficial for male function or antagonistic to female function, flourished on the evolving Y chromosome despite the deterioration of more generalized genes which lacked the DNA repair benefits of meiosis.
This evolution of the modern X and Y chromosomes was initiated by the emergence of a male sex-determining gene (now known as SRY) on what was originally an ordinary pair of autosomes (Figure 5). Genes associated with the non-recombining SRY region that were specifically beneficial for male function or antagonistic to female function, flourished on the evolving Y chromosome despite the deterioration of more generalized genes which lacked the DNA repair benefits of meiosis.
What are the genetic causes of male infertility?
Chromosomal abnormalities in males, such as translocations and inversions, which can be found with routine karyotyping, are found in approximately 1% of azoospermic males. However, the most common chromosomal abnormalities in azoospermic men are abnormalities involving the sex chromosomes, which are found in approximately 4% of these men. Klinefelter’s syndrome, in which patients show a 47,XXY karyotype, is the most frequent form. Even in these cases, we can usually find a few rare sperm adequate for fertility using ICSI.
However, the percentage of male infertility that can be explained by karyotyping alone is low, this being mainly due to the low resolution of routine cytogenetic studies. It was not until the development of modern molecular techniques such as polymerase chain reaction (PCR) that we could study the genetic causes of male infertility with much greater detail. Since then, many more genetic abnormalities, such as micro-deletions and point mutations, have been described in infertile males, with most research focusing on the role of genes on the human Y chromosome. We have shown that the long arm of the Y chromosome contains not one but many distinct deletion intervals and at least 60 genes belonging to nine gene families whose exclusive function is in spermatogenesis.
In fact, the deletion frequency of one or more of these regions on the Y chromosome in men with azoospermia or severe oligozoospermia is approximately 15% (Figure 1). After our initial report, many laboratories throughout the world have reported on these sub-microscopic deletions of the Y chromosome in azoospermic and severely oligozoospermic men. In fact, deletion screening of the Y chromosome is now considered standard practice for severely oligozoospermic and azoospermic patients undergoing assisted reproduction in most countries in the world.
However, the percentage of male infertility that can be explained by karyotyping alone is low, this being mainly due to the low resolution of routine cytogenetic studies. It was not until the development of modern molecular techniques such as polymerase chain reaction (PCR) that we could study the genetic causes of male infertility with much greater detail. Since then, many more genetic abnormalities, such as micro-deletions and point mutations, have been described in infertile males, with most research focusing on the role of genes on the human Y chromosome. We have shown that the long arm of the Y chromosome contains not one but many distinct deletion intervals and at least 60 genes belonging to nine gene families whose exclusive function is in spermatogenesis.
In fact, the deletion frequency of one or more of these regions on the Y chromosome in men with azoospermia or severe oligozoospermia is approximately 15% (Figure 1). After our initial report, many laboratories throughout the world have reported on these sub-microscopic deletions of the Y chromosome in azoospermic and severely oligozoospermic men. In fact, deletion screening of the Y chromosome is now considered standard practice for severely oligozoospermic and azoospermic patients undergoing assisted reproduction in most countries in the world.
Y chromosome In Humans and Apes
Comparing spermatogenesis in humans, chimpanzees and gorillas has always been fascinating. Chimpanzees, which weigh only about 100 pounds have enormous 8 centimeter diameter round (not oval) testes with sperm counts of over a billion per ml. Yet gorillas, which weight as much as 600 pounds or more, have tiny testes, very poor spermatogenesis, and in the sparse literature on gorilla testicular histology, in the majority of cases have what appears to be Sertoli cell only. Humans, the closest living relatives to chimpanzees and gorillas, fall somewhere in between.
The generally accepted reason for this massive discrepancy in spermatogenesis between these three closely related species lies in their differing mating patterns. Chimpanzees congregate in troupes of 30 to 40 in an extended family wherein any female who goes into heat is instantly mounted by every single male in the troupe. Therefore, there is an intense “competition” between the sperm of the different males to see which one will fertilize the females’ eggs. It is far more likely that the male with the highest sperm count, and the biggest testicles, will become the father of the male offspring, because of the high degree of “sperm competition” in chimpanzees.
In gorillas, it is the opposite. Any female is permanently attached to just one single silverback alpha male, and if she ever gets pregnant, it will have to be with his sperm only. So in gorillas there is no sperm competition. That results in small testes with very low sperm counts in these otherwise huge, very macho animals. But why is that? The answer lies in the peculiar instability of the non-recombining Y chromosome.
The multiple nucleotide sequence direct and inverted repeats (amplicons and palindromes) are where all the testis specific spermatogenesis genes on the Y are located. These areas are prone to frequent deletions caused by non-homologous, or “illegitimate” homologous recombination with itself, resulting in drop-outs of often huge chunks of DNA, making the concentration of spermatogenesis genes on the Y chromosome have a very fragile existence. So without sperm competition, sperm counts over eons of time are likely to go down.
Most intriguing is to compare the human Y chromosome to the chimpanzee Y chromosome, both of which have been fully and accurately sequenced. Unfortunately, the gorilla Y has not yet been sequenced. Nonetheless some interesting differences are noted between the human Y and the chimpanzee Y. Firstly, the chimpanzee Y has many more amplicons and palindromes than the human, and nonetheless, much fewer ampliconic genes (25 compared to 60). Furthermore, the chimpanzee Y is missing a gene (PRY) that is present on AZFc in the human, but completely absent in the chimpanzee. Furthermore, this gene has also been found to be absent in rare humans who have incredibly high sperm counts, approaching half a billion. Thus, comparing the super fertile chimpanzee Y chromosome to its less fertile human cousin, can help us understand better the genetic control of spermatogenesis in our infertile male patients.
The generally accepted reason for this massive discrepancy in spermatogenesis between these three closely related species lies in their differing mating patterns. Chimpanzees congregate in troupes of 30 to 40 in an extended family wherein any female who goes into heat is instantly mounted by every single male in the troupe. Therefore, there is an intense “competition” between the sperm of the different males to see which one will fertilize the females’ eggs. It is far more likely that the male with the highest sperm count, and the biggest testicles, will become the father of the male offspring, because of the high degree of “sperm competition” in chimpanzees.
In gorillas, it is the opposite. Any female is permanently attached to just one single silverback alpha male, and if she ever gets pregnant, it will have to be with his sperm only. So in gorillas there is no sperm competition. That results in small testes with very low sperm counts in these otherwise huge, very macho animals. But why is that? The answer lies in the peculiar instability of the non-recombining Y chromosome.
The multiple nucleotide sequence direct and inverted repeats (amplicons and palindromes) are where all the testis specific spermatogenesis genes on the Y are located. These areas are prone to frequent deletions caused by non-homologous, or “illegitimate” homologous recombination with itself, resulting in drop-outs of often huge chunks of DNA, making the concentration of spermatogenesis genes on the Y chromosome have a very fragile existence. So without sperm competition, sperm counts over eons of time are likely to go down.
Most intriguing is to compare the human Y chromosome to the chimpanzee Y chromosome, both of which have been fully and accurately sequenced. Unfortunately, the gorilla Y has not yet been sequenced. Nonetheless some interesting differences are noted between the human Y and the chimpanzee Y. Firstly, the chimpanzee Y has many more amplicons and palindromes than the human, and nonetheless, much fewer ampliconic genes (25 compared to 60). Furthermore, the chimpanzee Y is missing a gene (PRY) that is present on AZFc in the human, but completely absent in the chimpanzee. Furthermore, this gene has also been found to be absent in rare humans who have incredibly high sperm counts, approaching half a billion. Thus, comparing the super fertile chimpanzee Y chromosome to its less fertile human cousin, can help us understand better the genetic control of spermatogenesis in our infertile male patients.
What is Y chromosome and male infertility?
Along with the development of ICSI in 1993, our center was the first to study the Y chromosome and male infertility, and why tiny amounts of sperm are often found in the testes of azoospermic men previously thought to be making no sperm. You have probably heard a lot about the Y chromosome. It is what determines that a male is a male. We discovered with our first scientific paper on this in 1995 that the Y chromosome contains many genes that are involved in spermatogenesis, and deletions involving these genes are often found in infertile males. There has been a great deal of unknowledgeable discussion about our discovery of these sperm producing genes on the Y and a lot of misinformation. So in this page, I will try to clear up the confusion so you will understand better the genetics of male infertility. Our sequencing the DNA of the Y gives us a deep perspective about infertility genes that are widespread throughout the genome and which are also involved in transmitting infertility to future generations. A benefit of understanding the Y chromosome is it will help us to comprehend why men who are seemingly azoospermic usually have some residual tiny amount of spermatogenesis that can be used for successful ICSI. More importantly, it will expose the futility of trying to increase sperm count with drugs or varicocoele surgery.
Until two decades ago, there were no treatment options for infertile couples when the male had severely impaired spermatogenesis. In fact, there are still no clinical therapies to correct deficient spermatogenesis. Since the introduction of ICSI by us and the Brussels Dutch-Speaking Free University in 1992, however, there has been a revolution in our thinking about male infertility. Infertile couples with the most severe cases of male infertility, even with apparently 100% abnormal morphology and even just rare spermatozoa in the ejaculate, can now have pregnancy and delivery rates not apparently different from conventional IVF with normal sperm.
In 1993, we were the first to introduce microsurgical epididymal sperm aspiration (MESA) in conjunction with ICSI for the treatment of obstructive azoospermia. A few months later, TESE (testicular sperm extraction) was also found to be effective for the majority of cases of non-obstructive azoospermia as well. The reason is that approximately 60% of azoospermic men with presumably no sperm production actually do have a minute amount of sperm production in the testis that is just not quantitatively sufficient to spill over into the ejaculate, but which is adequate for ICSI. Thus, even men with spermatogenesis so deficient in quantity that no sperm at all can reach the ejaculate, could now have children with the use of TESE-ICSI.
Until two decades ago, there were no treatment options for infertile couples when the male had severely impaired spermatogenesis. In fact, there are still no clinical therapies to correct deficient spermatogenesis. Since the introduction of ICSI by us and the Brussels Dutch-Speaking Free University in 1992, however, there has been a revolution in our thinking about male infertility. Infertile couples with the most severe cases of male infertility, even with apparently 100% abnormal morphology and even just rare spermatozoa in the ejaculate, can now have pregnancy and delivery rates not apparently different from conventional IVF with normal sperm.
In 1993, we were the first to introduce microsurgical epididymal sperm aspiration (MESA) in conjunction with ICSI for the treatment of obstructive azoospermia. A few months later, TESE (testicular sperm extraction) was also found to be effective for the majority of cases of non-obstructive azoospermia as well. The reason is that approximately 60% of azoospermic men with presumably no sperm production actually do have a minute amount of sperm production in the testis that is just not quantitatively sufficient to spill over into the ejaculate, but which is adequate for ICSI. Thus, even men with spermatogenesis so deficient in quantity that no sperm at all can reach the ejaculate, could now have children with the use of TESE-ICSI.
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