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Sperm DNA Damage Linked To Increased Risk of Pregnancy Loss after IVF and ICSI

Earlier studies have indicated that spermatozoa of infertile men possess considerably more sperm DNA damage than that of fertile men, which could adversely affect both natural reproduction and assisted reproduction technology (ART) outcomes. Since the use of ART to treat infertility has increased substantially from its introduction in the US, in 1981, there is a huge concern regarding the safety of using DNA-damaged spermatozoa. Now, a recent study published online in the journal, Human Reproduction, demonstrates that sperm DNA damage is associated with a significantly enhanced risk of pregnancy loss following in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI).
Armand Zini from the St Mary’s Hospital Center, Canada and coworkers conducted a systematic review and meta-analysis of studies involving sperm DNA damage and pregnancy loss after IVF and/or ICSI treatment to determine the relationship between the two. The researchers analyzed 11 studies, which included 808 IVF and 741 ICSI cycles of treatment, resulting in 640 pregnancies (345 with IVF and 295 with ICSI) and 122 pregnancy losses. From the estimates of pregnancy loss, two by two tables were constructed and odds ratios (ORs) were calculated to examine the association. It was found that the combined odds ratio was 2.48, suggesting that damage to spermatozoa DNA raises the risk of pregnancy loss in IVF and ICSI cycles. The data indicates that sperm DNA damage has to be evaluated prior to ARTs to achieve better outcomes and also forms a basis for further investigations to validate the findings.
Recently, Bhattacharya SM (International Urology and Nephrology, 2008) conducted a study to examine the link between different sperm parameters and repeated unexplained early pregnancy loss. Semen samples obtained from male partners of 74 couples with a history of repeated pregnancy loss were assessed according to WHO criteria and the DNA integrity in each case was evaluated using Acridine Orange staining test. A comparison of the results was also drawn by studying semen samples obtained from 65 husbands of proven fertility. It was noted that there were a lack of statistically significant differences between the two groups in the following criteria: age of husbands, total count per ejaculate, sperm concentration, and rapid progressive motility of sperms. However, DNA integrity value, percentage of motile sperm and total motile sperms per ejaculate, were different in the two groups. Based on the findings, it was concluded that repeated embryonic or early fetal loss is associated with sperm DNA-integrity damage, implying that sperm DNA damage may be a key paternal factor for predicting pregnancy outcomes.
To determine the relationship between sperm DNA fragmentation in IVF/ICSI patients, ART outcome, and sperm parameters, Borini and colleagues (Human Reproduction, 2006) conducted a study on 132 men undergoing ART. The scientists found that the embryo post-implantation development in ICSI procedures is affected by sperm DNA fragmentation; with a high fragmentation rate compromising embryo viability, and thereby leading to pregnancy loss.
Sperm DNA damage is attributed to various intra-or extratesticular factors such as chemotherapy, radiation therapy, genital tract inflammation, testicular hyperthermia, varicoceles, cigarette smoking and environmental toxins. Although previous studies have found no consistent relation between sperm DNA damage and fertilization rates during IVF or ICSI, the recent research provides evidence that sperm DNA damage may be associated with an increased risk of significant spontaneous abortion. Substantiating the current research with further larger trials may help in the development of stringent processes for selecting sperms and embryos during ART to alleviate the adverse effects related to sperm DNA damage.
References
1. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008 Dec;23(12):2663-8. Epub 2008 Aug 29.
2. Bhattacharya SM. Association of various sperm parameters with unexplained repeated early pregnancy loss–which is most important? Int Urol Nephrol. 2008;40(2):391-5.
3. Borini A, Tarozzi N, Bizzaro D, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006 Nov;21(11):2876-81. Epub 2006 Jun 22.

Dominant Follicle Diameter Helps Select Optimal Day for Oocyte Retrieval in IVM Cycles

In vitro maturation (IVM), a novel assisted reproduction technique, reduces risks associated with in vitro fertilization (IVF) as the eggs are retrieved, matured and fertilized in vitro prior to implantation, thereby eliminating ovarian stimulation. However, the factors predisposing the success or failure of IVM cycles are unclear. Now, a recent study published in the December issue of the journal, Human Reproduction suggests that dominant follicle (DF) size of ≤14mm at oocyte retrieval following human chorionic gonadotropin (hCG) priming improves pregnancy outcomes in cycles programmed for IVM treatment.
Weon-Young Son from the McGill University, Montreal, and coworkers conducted a study on 160 women with polycystic ovaries (171 cycles) to compare the DF size at oocyte retrieval after hCG priming with IVM outcome. When the endometrial thickness reached a minimal of 6 mm, the researchers subcutaneously administered 10,000 IU hCG, 35 to 38 hours prior to oocyte collection. The retrospective analysis was performed in 3 study groups based on the DF diameter: group 1, with a diameter of ≤10 mm; group 2, between 10 and 14 mm; and group 3 of >14mm. In the corresponding 3 groups, 6.9%, 10.6%, and 15.1% of the in vivo matured oocytes were collected, suggesting a positive correlation between the size and number of oocytes.
Results showed that among the sibling immature oocytes extracted in the 3 groups, the rates of IVM, fertilization and embryo development were similar. It was found that group 3 exhibited a lower clinical pregnancy rate (17.1%) compared to group 2 (40.3%). Furthermore, groups 1 (13.6%) and 2 (14.3%) had higher implantation rates than group 3 (4.9%). Based on the study findings, the researchers proposed DF ≤14mm as the optimal oocyte retrieval time for IVM cycles, as DF >14 mm may detrimentally affect the sibling immature oocytes.
Earlier, the same group of researchers conducted a retrospective study (Human Reproduction, 2008) to investigate if an extension in the time interval between hCG priming and immature oocyte retrieval enhances the oocyte maturation rate after IVM. The assisted reproduction technique was performed on 113 polycystic ovary syndrome patients (120 cycles) and the oocytes were collected at either 35 hours (group 1=76) or 38 hours (group 2 = 44) following 10,000 IU of hCG priming. The oocyte maturity was analyzed after the retrieval and the culture of the immature oocytes was performed till day 2 using IVM medium. It was found that the number of in vivo matured oocytes was considerably lower in group 1 (13.6%) compared to group 2 (7.3%). Also, group 2 exhibited a higher oocyte maturation rate after day 1 (46.3 vs. 36.0%), clinical pregnancy (40.9 vs. 25%) and implantation rates (15.6 vs. 9.6%) than group 1. Based on the findings, the scientists suggested that extending the time of hCG priming from 35 hours to 38 hours for oocyte retrieval could improve the pregnancy outcome of IVM cycles.
In vitro maturation of immature oocytes collected from unstimulated ovaries is an assisted reproduction technology that is extensively being studied. Some of the advantages of IVM over IVF are that it is less expensive, has shorter treatment regimen, and does not require the use of hormonal fertility drugs for ovarian stimulation. It may thereby eliminate the risk of developing ovarian hyperstimulation syndrome and multiple pregnancies.
Several previous studies have indicated that controlled ovarian stimulation in combination with in vitro fertilization cycles provide better results compared to in vitro maturation techniques. Now, the identification of the optimal hCG priming time and dominant follicle size for oocyte retrieval may help in enhancing the success rates of the novel IVM technique with fewer adverse effects compared to IVF.
References
1.Son WY, Chung JT, Herrero B, et al. Selection of the optimal day for oocyte retrieval based on the diameter of the dominant follicle in hCG-primed in vitro maturation cycles. Hum Reprod. 2008 Dec;23(12):2680-5. Epub 2008 Sep 4.
2.Son WY, Chung JT, Chian RC, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008 Sep;23(9):2010-6. Epub 2008 Jun 12.

Pretreatment with Transdermal Testosterone may Enhance Ovarian Response to FSH

The synergistic effects of androgens and follicle stimulating hormone (FSH) on folliculogenesis, a process critical for assisted reproduction techniques, have been previously established in primates. Now, a recent randomized clinical trial published in the journal Human Reproduction demonstrates that pretreatment with transdermal testosterone enhances the follicular response in poor IVF responders compared to the high-dose gonadotropin and minidose GnRH agonist protocol.
Francisco Jose Fabregues Gasol, from the Institut Clínic of Gynecology, Obstetrics and Neonatology, University of Barcelona, Spain, and colleagues, conducted a randomized trial to explore the efficacy of transdermal testosterone pretreatment in poor IVF responders. Sixty-two infertile women with a history of poor follicular response to IVF cycle were equally divided into two groups for their second IVF treatment. The first group received transdermal testosterone prior to standard ovarian stimulation, along with gonadotropin under pituitary suppression. On the other hand, the second group was administered with high-dose gonadotropin, along with a low-dose gonadotropin releasing hormone (GnRH) agonist protocol for ovarian stimulation.
Investigators observed that the first group had 32.2% cycles with low response, as compared to 71% in the other group. Also, ovum retrieval was more in the first group of patients (80.6%) in contrast to the second group (58.1%), with statistically significant difference (81.2% vs. 41.1%) in patients with normal basal FSH levels. The study results showed that the ovarian sensitivity to FSH and the response of follicles to gonadotropin treatment could be enhanced through transdermal testosterone pretreatment in poor IVF responders.
Earlier, Balasch and colleagues (Human Reproduction, 2006) conducted a self-controlled, therapeutic clinical trial on 25 infertile women with a history of poor follicular response, leading to cancellation of first and second IVF cycles. It was observed that pretreatment with transdermal testosterone could be an effective approach for poor IVF responders with normal basal FSH concentration but poor controlled ovarian stimulation response.
In a contradictory study, Massin, et al. (Human Reproduction, 2006) observed that testosterone administration does not significantly affect the ovarian response to FSH. The researchers conducted a double-blind study on women with a background of low response to controlled ovarian stimulation and a low hormonal ovarian reserve, to evaluate the effects of androgen application. The subjects were randomized to receive either transdermal testosterone or placebo gel for 15 days prior to gonadotropin administration for a second IVF cycle. Both cycles involved identical GnRH analogue and equal FSH daily doses. Plasma testosterone levels were substantially enhanced, with no similar effects on the antral follicular count in the test group. There was no significant difference in both the groups with regard to the main ovarian response parameters such as pre-ovulatory follicular number, and the count of total and mature oocytes and embryos. Based on their findings the investigators emphasized on further clinical trials to study the effects of optimal dose and duration for testosterone administration.
Conditions, such as high body mass index, pelvic adhesions, prior ovarian surgery, or progressive age, could be related with low ovarian response to gonadotropin treatment. The outcome of an IVF treatment is directly dependent on the number of embryos available. Poor ovarian response could lead to low embryo count, resulting in decreased pregnancy rates. Kailasam and colleagues (Human Reproduction, 2004) defined poor response in women aged <40 years, as cancellation of the cycle in patients on ≥300 IU FSH/day, (<3 pre-ovulatory follicle development), or the requirement for the total administration of ≥3000 IU FSH for sufficient follicular recruitment, substantiating oocyte retrieval.
Poor ovarian response to standard FSH treatment is a major concern in assisted reproduction processes. The current study, which demonstrates the enhanced ovarian sensitivity to gonadotropin in poor IVF responders, by pretreatment with transdermal testosterone, could serve as a novel approach to achieve enhanced success of IVF treatment.
References
1. Fábregues F, Peñarrubia J, Creus M, et al. Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial. Hum Reprod. 2008 Dec 3. [Epub ahead of print]
2. Balasch J, Fábregues F, Peñarrubia J, et al. Pretreatment with transdermal testosterone may improve ovarian response to gonadotrophins in poor-responder IVF patients with normal basal concentrations of FSH. Hum Reprod. 2006 Jul;21(7):1884-93.
3. Massin N, Cedrin-Durnerin I, Coussieu C, Galey-Fontaine J, Wolf JP, Hugues JN. Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique–a prospective, randomized, double-blind study. Hum Reprod. 2006 May;21(5):1204-11.
4. Kailasam C, Keay SD, Wilson P, Ford WC, Jenkins JM. Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome. Hum Reprod. 2004 Jul;19(7):1544-7.

Cryptorchidism May be Associated with Genetic Mutations

Cryptorchidism, a common congenital defect of the male genitalia that affects 3-4% of full-term infants and 30% of those born prematurely, poses a risk for infertility and testicular cancer. However, the exact etiology and pathogenesis of cryptorchidism are not clearly known. Now, a recent study published in the Journal of the American Medical Association has identified a potential link between cryptorchidism and genetic alterations such as insulin-like factor 3 (INSL3) receptor gene mutations and Klinefelter syndrome.
Alberto Ferlin from the Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Italy, and coworkers, conducted the case-control study on 600 male infants in Italy during 2003 to 2005, to investigate the rate of genetic alterations in cryptorchidism. Three hundred noncryptorchid boys between 1 to 4 years were selected as controls. Follow-up of the subjects was done for 2 to 3 years and those with persistent cryptorchidism were treated with orchidopexy.
Study results showed that mutations ranged from low in boys with cryptorchidism (2.8%), to high in those with persistent cryptorchidism (5.3%) and bilateral cryptorchidism (8.3%), compared to controls (0.3%). The calculated odds for having genetic alteration in boys with persistent cryptorchidism were more than 17 times; however, there was lack of mutations in boys with low gestational age or low birth weight and those who had spontaneous descent of the testes. The researchers found that Klinefelter syndrome and INSL3 receptor gene mutations were most frequently associated with cryptorchidism, suggesting a significant relationship between the disease and genetic alterations.
Early studies have indicated that INSL3 plays a key role in testicular descent, with mutations in the gene or its G protein-coupled receptor (leucine-rich repeat, containing G protein-coupled receptor (LGR8)) likely to be associated with cryptorchidism.
Ferlin, et al. (Molecular Human Reproduction, 2006) conducted a study to investigate the hypothesis pertaining to the relationship between INSL3 mutations and the signs of testicular dysgenesis syndrome (TDS), characterized by undescended testis, poor semen quality, testis cancer, and hypospadias. The analysis was performed on 967 subjects with maldescended testes and/or infertility and/or testicular cancer and 450 controls. The researchers also conducted in vitro functional analysis of genetic alterations (R4H, W69R, and R72K) by observing the increase of INSL3-dependent cAMP (cyclic adenosine monophosphate) in cells that express LGR8. It was found that 1.9% of the subjects had 6 INSL3 mutations, with no similar finding in the controls. Based on the findings, it was suggested that a significant link may exist between INSL3 gene alterations and TDS syndrome signs; although, a definite causative role was not established.
Although cryptorchidism or undescended testicle may occur bilaterally, it commonly affects the right testes. A combination of factors such as maternal health, genetics, and environment may play an important role in its development, but the exact cause is unknown. Generally, the condition resolves by itself but sometimes may require orchidopexy to relocate the testis into the scrotum.
Substantiating the current research, which identifies the association between undescended testicles and genetic mutations in INSL3 receptor gene and Klinefelter syndrome, with further larger studies, may help to elucidate the underlying disease mechanism. Further, this may facilitate in developing novel therapeutic strategies for patients with persistent and bilateral cryptorchidism, thereby reducing the burden associated with male infertility.
References
1. Ferlin A, Zuccarello D, Zuccarello B, Chirico MR, Zanon GF, Foresta C. Genetic alterations associated with cryptorchidism. JAMA. 2008 Nov 19;300(19):2271-6.
2. Ferlin A, Bogatcheva NV, Gianesello L, et al. Insulin-like factor 3 gene mutations in testicular dysgenesis syndrome: clinical and functional characterization. Mol Hum Reprod. 2006 Jun;12(6):401-6. Epub 2006 May 10.

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Duration of Embryo Cryopreservation Does Not Affect Pregnancy Outcome

A study in the latest online issue of Fertility and Sterility has reported that the length of embryo cryostorage does not adversely affect the post thaw survival rate or pregnancy outcome, suggesting it to be a safe and valuable adjunct to assisted reproduction technology (ART).
Sergio Oehninger, Director of the Division of Reproductive Endocrinology and Infertility, Jones Institute for Reproductive Medicine, Virginia, and coworkers, conducted the retrospective study to investigate the effect of cryostorage duration on embryo survival, implantation competence, and pregnancy outcome. The cryopreserved embryos were isolated from in vitro fertilization (IVF) patients, and recipients of oocyte donation cycles. Researchers analyzed a total of 11,768 cryopreserved embryos which had undergone at least one thaw cycle during 1986 to 2007. Post thaw survival proportion and implantation, miscarriage, clinical pregnancy, and live birth rates were considered as the primary outcomes of the study.
The study findings showed that the extent of cryostorage duration for IVF or oocyte donation cycles did not significantly affect the post thaw survival of embryos (frozen at pronuclear or cleavage stages), implantation competence, or pregnancy outcomes. Logistic regression analysis, however, confirmed that factors, such as stage of oocyte, number of embryos transferred and survival proportion, positively predict pregnancy outcomes.
Earlier, Machtinger, et al. (Gynecological Endocrinology, 2002) conducted a case-control study to evaluate the impact of long-term cryopreservation of embryos on its survival, and implantation rate. The study compared 101 women, implanted with their embryos which were cryopreserved for 2–9 years, and the same number of women (control) implanted with embryos stored for 6 months or less. The implantation rate was found to be 4.5% and 5.5% in the study and control groups, respectively. Based on the similar implantation rate observed in both the groups, the researchers concluded that prolonged cryopreservation, do not have an adverse impact on embryo survival and could thereby be an effective option for embryo storage in ARTs.
Embryo cryopreservation plays a major role in the overall outcome achieved by assisted reproduction programs. The procedure also facilitates an improved cumulative success rate for IVF, preventing ovarian hyperstimulation syndrome (OHSS) and reducing the rate of multiple pregnancies. Although several researches suggest that long time preservation of embryos does not affect its survival rate and pregnancy outcome, the maximum duration up to which the embryo can remain in the frozen state for successful implantation, needs further investigation.
References
1. Riggs R, Mayer J, Dowling-Lacey D, et al. Does storage time influence postthaw survival and pregnancy outcome? An analysis of 11,768 cryopreserved human embryos. Fertil Steril. 2008 Nov 20. [Epub ahead of print]
2. Machtinger R, Dor J, Levron J, et al. The effect of prolonged cryopreservation on embryo survival. Gynecol Endocrinol. 2002 Aug;16(4):293-8.

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Surrogacy Law Must Be Reviewed in the UK

Pressure for a review of surrogacy law is mounting in legal, media and
political quarters following the case of Re X & Y (Foreign Surrogacy) 2008.
The case - the first to test thelaw for British couples going abroad for surrogacy
- has highlighted the complexity and confusion surrounding surrogacy law in the UK.
The case hit the headlines after twins, biologically the children of a
British father and an anonymous egg donor and carried by a Ukrainian
surrogate mother, were left parentless and stateless by a conflict between
English and Ukrainian law. The British commissioning parents were not
treated as the twins' parents under English law, despite the British
father's biological paternity. The twins could have faced a childhood in a
Ukrainian orphanage if the High Court had not made a groundbreaking decision
to authorise the payment of £23,000 made to the surrogate mother.
The issues in the case go to the very core of society's attitude to
fertility treatment and highlight the problems with the current constraints
on surrogacy in the UK, particularly in the wake of increasing
permissiveness of commercial surrogacy in foreign jurisdictions. The
landmark legal judgment has ramifications for all those involved in
fertility practice, including patients, their legal advisers, clinicians and
the HFEA.
The case follows hard on the heels of recent parliamentary debates on
the Human Fertilisation and Embryology Act 2008. The government indicated in
those debates that it was minded to review the law and regulation of
surrogacy, but it fell short of tackling the issue head-on. This was a lost
opportunity to overhaul the inherent problems and inconsistencies with
English surrogacy law.
The case of Re X and Y highlights quite how significant this omission
was. The risk of many more couples ending up in a similar nightmare is
worrying. More British couples are travelling abroad for treatment, for
reasons including the acute shortage of egg donors in the UK and
restrictions on commercially-arranged surrogacy which make it difficult to
find a suitable surrogate mother in the UK. Mr Justice Hedley acknowledged
this trend, saying 'more and more couples are likely to be tempted to follow
the applicants' path to commercial surrogacy in those places where it is
lawful'.
The problem is that many foreign systems of law take a very different
approach to surrogacy, so that children are born following arrangements
which would not be permitted in the UK. In Re X & Y, the British couple had
paid the surrogate mother 27,000 Euros (£23,000), far more than the
'reasonable expenses' permitted under UK law. The High Court's decision to
authorise the payments was a watershed, but the court made it clear that the
UK maintains a public policy against commercial surrogacy and that every
case will be decided on its own facts. Other British couples who conceive
through foreign surrogacy can therefore expect to face a similar legal
battle to the parents in Re X and Y.
Of equal concern, Mr Justice Hedley acknowledged that the British couple
in Re X and Y had made diligent enquiries about parenting options and made
what they felt was an informed decision about entering into a surrogacy
arrangement in the Ukraine. He commented that none of the legal difficulties
the couple experienced were 'foreshadowed in any of the extensive enquiries
they had made before leaving this country, whether on Home Office websites
or the information given by the bodies who advised them in the United
Kingdom or the information given to them in and through the Ukrainian
Hospital'. There is currently a dire lack of good quality information about
the legal treatment of international surrogacy arrangements, Mr Justice
Hedley commenting that 'the quality of information currently available is
variable and may, in what it omits, actually be misleading'.
Fertility practitioners and regulatory bodies beware. Following Re X
and Y, relevant professionals (and regulatory bodies) in the UK will be
expected to provide patients with much better information about the legal
complications of foreign surrogacy. Re X and Y highlights quite how
dangerous it can be for patients (and perhaps their doctors) to focus
exclusively on the goal of conceiving and to give too little thought to the
legal consequences that may follow after their long-awaited child is born.
Surrogacy remains a sensitive and difficult subject and there needs to
be greater awareness of the complex legal issues. Those working with
fertility patients can also play their part for a better future by
increasing pressure for a review of surrogacy law in the UK.

- By Louisa Ghevaert, Associate Solicitor at Lester Aldridge LLP. Louisa
works with Natalie Gamble and represented the parents, together with
Natalie, in the Re X and Y case. For further information see
www.lesteraldridge.com/services/private/fertility/index.asp

Jacqueline Gold: I'm just so lucky to be pregnant at 48

Jacqueline Gold likes to joke that she has lived her whole life "backwards". At 48, at the peak of an enormously successful career – she is CEO of Gold Group International (which owns Ann Summers) and one of the most powerful women in British retailing – she is about to fulfil a dream that she put on hold as a young woman. Finally, at an age when most women are approaching menopause, Jacqueline is settling into her first pregnancy.
"I left home when I was 18, got married when I was 20 and started the business when I was 21 – all things that people tend to do later in life. I did the partying that most people do in their 20s in my 30s after my marriage broke down and of course here I am at 48 – five months pregnant and engaged to be married," she says, placing a small, manicured hand on the bump that already dominates her 5ft 2in frame.
Delicately pretty and softly spoken, it is difficult to believe that this woman is responsible for turning the male-dominated business started by her father David into a female-friendly preserve with a £115 million annual gross turnover. She attributes her business success to a combination of hard work, determination and creativity; qualities, she admits with a rueful smile, that she has also had to draw on in her quest to start a family.
Because, like a great many other ambitious women of her generation, Jacqueline always felt that she would have children "when the time felt right". But when it finally did – seven years ago when she met her banker fiancé Dan Cunningham, 31 – she was in her forties and infertility had become a major issue.
"I feel that evolution hasn't kept up with women," she says. "We live longer, we are healthier, we have careers and we are just not ready to have babies at the age of 20. I think it's such a shame that our bodies haven't evolved with us so that we can be fertile longer"
Jacqueline and Dan embarked on their first round of IVF in 2002 at a private clinic near the home they share in Kent. It was not a happy experience and when it failed they went to Britain's leading private IVF unit at the Lister Hospital in London where they had two more unsuccessful attempts. "The strain that IVF puts on your relationship is just incredible," she says. "It is a hard process and the disappointment when it fails is so overwhelming that a lot of couples have problems, and in 2006 it affected Dan and I so badly that we parted for a while."
When they got back together they decided to try IVF once more but this time they would go to America where the process is more advanced. "We had all the appointments over the phone here in the UK and all the medical checks and blood tests were done here and the results faxed over to the clinic in San Francisco. It wasn't until the end of three months that we finally flew out to the States late last August for the IVF."
They flew home shortly after the procedure unaware of whether or not they had been successful. Ten days later Jacqueline went for the blood test that would – when the results had been faxed through to America – reveal if she was pregnant.
"I remember driving to the hospital to have that test and being so nervous and so tense that I couldn't see properly, it was as if my sight had been impaired. I had the test at 8.30 in the morning but because of the time delay I had to wait until the evening for the result to come through. Dan and I sat by my computer in my office in absolute agony and it was just incredible when that email came through and it said 'Congratulations you are pregnant'."
Jacqueline admits that for the first few weeks of her pregnancy her elation was tempered by the fear that she might miscarry. But at 12 weeks – at the point at which she was beginning to feel safe – doctors discovered a problem.
"I am carrying twins but sadly one of them will not make it," she says. "When we found out it was devastating because even at that early stage you are very attached. I know people will say 'Yes but you have still got one healthy baby' but it doesn't work like that. It took me a while to come to terms with it. I took a few days off work and then I pulled myself together and thought 'OK, now I have got to concentrate on the healthy baby, that is my priority'."
The rare complication in Jacqueline's pregnancy means that she has to be very closely monitored, and scanned every two weeks.
"When we found out we were given the choice to have a selective termination immediately but because that would put the other baby at risk we decided to leave things as they were. At the moment they are planning on leaving me until I am 32 weeks, and then doing a selective reduction. But I may have to go to full term, which could be quite an emotional and traumatic experience."
It is a measure of Jacqueline's courage that she is prepared to talk openly about the problems she faces in her first pregnancy. She hopes that her story will inspire other women who may have had a negative IVF experience to pursue their dream. The fact that her own successful IVF outcome has brought with it new anxieties doesn't, she insists, make it any less exciting. She is absolutely determined to enjoy the experience of pregnancy.
"It's really strange but I just have this very good feeling. I know I face lots of challenges along the way but I am very positive. At first when I used to talk about the baby to Dan he would stop me and say 'let's not get ahead of ourselves'. We got to the point where I said [to Dan] 'I think if things go wrong we will be really devastated but I don't want to get to the end of my pregnancy and think all I did was worry when I should have been relishing every moment of being pregnant'."
Jacqueline is still nervous about thinking too far in the future – she and Dan decided not to know the sex of their healthy baby because they think the surprise will add excitement and ease the pain of what could be a difficult birth –- but she longs to be a mother. She will continue as CEO of the company but with the right help – and an office at home – she wants to be "totally" involved in raising her child.
She will have reached the age of 60 by the time her child is 12, but says that she is not concerned by the fact that she will be a pensioner while her child is an adolescent – or about society's unease about older mothers. "I think I will be a good mother," she says. "I don't want that to sound big-headed or arrogant. Some people might be concerned about my age but I believe I have much more to give a child now than I would have done when I was 20. The biggest part of me wants to give my child love, warmth and the security of a happy childhood. I will just be so lucky to have the chance to do that.

Mother of baby born free of breast cancer gene hails 'priceless' procedure

The mother of Britain's first baby selected genetically to be free of a breast cancer gene has hailed the prodecure as "priceless".
She likened the disease to a sword of Damocles hanging over her family and hoped her daughter's birth would help other families. Her baby, born last week, grew from an embryo screened to ensure it did not contain the faulty BRCA1 gene, which passes the risk of breast cancer down generations. Any daughter born with the gene has a 50 per cent to 85 per cent chance of developing breast cancer. The birth has sparked debate about the ethics of embryo screening.
The 26-year-old mother, who refused to be named, said she decided to undergo the screening process after seeing all her husband's female relatives have the disease. Speaking to The Sunday Times, she said: "To be able to look at our daughter and to know that she doesn't have the gene is a massive sigh of relief for us.
"We have eliminated that risk and that is priceless.
"Having watched my husband's family go through what they have been through, knowing that my daughter doesn't need to go through that, makes it all worthwhile.
"I hope this encourages others to do the same."
The baby's 28-year-old father said: "A massive amount of credit has to go to my wife for undergoing what was effectively an invasive procedure of IVF for a problem which wasn't her own but was from my side of the family.
"Talking about how we felt about it probably brought us closer together.
"There are many pitfalls my children may go through in life that I cannot predict for them.
"We do know about this one and that is why we felt a duty to do something about it."
Doctors at the University College London hospital, where the mother received IVF treatment, said they were on Friday that he was "absolutely delighted" at the breakthrough. Medical director at the Assisted Conception Unit Paul Serhal said: "This little girl will not face the spectre of developing this genetic form of breast cancer or ovarian cancer in her adult life.
"The parents will have been spared the risk of inflicting this disease on their daughter.
"The lasting legacy is the eradication of the transmission of this form of cancer that has blighted these families for generations."
The technique, known as pre-implantation genetic diagnosis (PGD) has already been used in the UK to free babies of inherited disorders such as cystic fibrosis and Huntington's disease. But breast cancer is different because it does not inevitably affect a child from birth and may or may not develop later in life. There is also a chance it can be cured, if caught early enough.
Permission to carry out PGD for breast cancer had to be obtained from the Human Fertilisation and Embryology Authority by the London clinic which performed the procedure. The body, which licenses IVF clinics and embryo research, gave the go-ahead after holding a public consultation. Doctors at the private clinic housed at University College Hospital conducted tests on 11 embryos by removing just one cell from each when they were three days old. Six embryos were found to carry the defective BRCA1 gene. Two embryos which were free of the gene were implanted, resulting in a single pregnancy.
Faulty genes are responsible for between 5 per cent and 10 per cent of the 44,000 cases of breast cancer that occur in the UK each year. BRCA1 and its sister gene BRCA2 are the two most commonly involved. Women with a defective BRCA1 or BRCA2 gene are up to seven times more likely to develop breast cancer than those without the mutations.

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The Frog & Golf

THIS IS HILARIOUS!


A man takes the day off work and
Decides to go out golfing.


He is on the second hole when he
Notices a frog sitting next to the green.


He thinks nothing of it and is
About to shoot when he Hears,



Ribbit 9 Iron.'



The man looks around and doesn't
See anyone.


Again, he hears, 'Ribbit 9 Iron.'


He looks at the frog and decides to
Prove the frog wrong, puts the
Club away, and grabs a 9 iron.



Boom!
He hits it 10 inches from the cup.


He is shocked.


He says to the frog,


'Wow that's amazing.


You must be a lucky frog, eh?


The frog replies,



'Ribbit Lucky frog.'




The man decides to take the frog
with him to the next hole.

'What do you think frog?'



The man asks.



'Ribbit 3 wood.'


The guy takes out a 3 wood and,
Boom! Hole in one.



The man is befuddled and doesn't know
What to say.


By the end of the day, the man golfed the
Best game of golf in his life and
asks the frog,



'OK where to next?'
The frog replies,


'Ribbit Las Vegas .


' They go to Las Vegas
and the guy says,


'OK frog, now What?'


The frog says, 'Ribbit Roulette.'


Upon approaching the roulette table,


The man asks,


'What do you think I should Bet?'


The frog replies,


'Ribbit $3000, black 6.'

Now, this is a
million-to-one shot to win, but
after the golf game the man
Figures what the heck.

Boom!


Tons of cash comes sliding back across the table.

The man takes his winnings and
buys the best room in the Hotel.


He sits the frog down and Says,


'Frog, I don't know how to repay you.
You've won me all this money and
I am forever grateful.'

The frog replies,

'Ribbit KissMe.'
He figures why not,

Since after all the frog did for Him,


He deserves it.



With a kiss, the frog turns into a
gorgeous 15-year-old girl.


'And that,

your honor, is how the girl
ended up in my room.



So help me God
Or my name is not William Jefferson Clinton.'

Peanuts again!

Genetic screening fails women trying for IVF birth

Genetic screening, often seen as the best hope for older women undergoing IVF treatment to have a child, is ineffective and actually reduces rates of pregnancies, scientists said on Wednesday.

The surprise finding from a controlled clinical trial involving 408 women is a major setback for a technology that is used increasingly in fertility clinics worldwide.

Couples aiming for a test-tube baby can pay between $3,000 (INR 150,000) and $5,000 (INR 250,000) for a preimplantation genetic screening test. The idea is to study the genetic make-up of embryos before transfer to the womb to make sure they are healthy and likely to survive.

But while the concept is very plausible, Dutch researchers found screening in women aged 35 to 41 years actually made matters worse.

After 12 weeks, only 25 percent of women undergoing in vitro fertilisation (IVF) whose embryos had been screened were pregnant, against 37 percent in the control group. Eventual live birth rates were also lower, at 24 versus 35 percent.

Just why screening cuts the chance of a viable pregnancy is unclear but Sebastiaan Mastenbroek from the Academic Medical Centre of the University of Amsterdam said the test itself might be to blame.

"It is possible that the biopsy of a cell from an early embryo on day three after conception hampers the potential of an embryo to successfully implant, though the effect of biopsy alone on pregnancy rates has not been studied," he said in a statement.
Usually, embryos will have reached the eight-cell stage of development by day three but sometimes there may be as few as four cells, which could in theory make the procedure riskier.

Other factors may be the limited number of chromosomes that can be analysed, which may lead to the transfer of embryos that appear normal but in fact contain faults, and the fact many embryos are "mosaic", where a single cell does not properly reflect the genetic make-up of the whole.

Mastenbroek and colleagues presented their work at the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Lyon, France.

The research was also published online by the New England Journal of Medicine, alongside a recommendation from the team that preimplantation should no longer be performed routinely in older women undergoing IVF therapy.

Fertility experts said the findings were a wake-up call for clinicians and showed the need for more research into the benefits, if any, of preimplantation genetic diagnosis (PGD).

Peter Braude, professor of obstetrics and gynaecology at Kings College London, said the work showed screening did not work in older mothers-to-be and similar studies were needed on whether it helped younger women with repeated IVF failure.

"Vulnerable patients should no longer be exploited financially under the impression that it works," he said.

Joep Geraedts, ESHRE’s chairman elect and a genetics expert at the Dutch-Belgian University Limburg, told Reuters in a telephone interview the new study would come as a shock, particularly in the United States, where PGD is widely used.

"No other medical procedure with such profound medical and ethical consequences has been so poorly studied," Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University, Baltimore, said.

The Aisle Seat

Two Pakistanis boarded a flight out of New Delhi.

One took a window seat and the other sat next to him in the middle
seat... Just before takeoff, a Sikh, an Indian Army NCO sat down
in the aisle seat.

After takeoff, the soldier kicked his milirary shoes off, wiggled his toes and
was settling in when the Pakistani in the window seat said, 'I need to get up
and get a coke.'

Don't get up,' said the Sardar, 'I'm in the aisle seat, 'I'll get it for you.'

As soon as he left, he picked up the Sardar's left shoe and spat in it.

When the Sardar returned with the coke, the other Paki said, 'That looks
good, I'd really like one, too.'

Again, the Sardar obligingly went to fetch it. While he was gone, the
other Paki picked up the Sardar's right shoe and spat in it.

When the Sardar returned, they all sat back and enjoyed the flight, the
Pakis finishing their cokes. As the plane was landing, the Sardar slipped
his feet into his shoes and knew immediately what had happened.

He leaned over and asked his Pakistani neighbors ...

''Why does it have to be this way?''
''How long must this go on . . . ?"

''This fighting between our nations . . . ?''

''This hatred . . . ?''

''This animosity . . . ?''

''This spitting in shoes...


Scroll down for the punch line!





















and pissing in cokes . . . ?''

New IVF Progesterone Delivery System Study

A leading Southern California Fertility center esteemed for their excellent IVF success rates and national reputation was recently selected as a participant in a national, multi-center study exploring new progesterone delivery systems to replace intramuscular injections. Patients going through in vitro fertilization (IVF) often describe the progesterone injections as the most difficult and painful part of the IVF cycle. For more than 30 years doctors have been seeking effective alternatives to these painful injections.

The study compares an FDA-approved vaginal progesterone, Endometrin, with a new formulation which is administered subcutaneously, similar to the relatively painless fertility drug injections. Patients will be randomized to receive either the vaginal or subcutaneous progesterone until the pregnancy test and then until about 10 weeks of pregnancy. In case of unacceptable side effects the patient will be offered an alternative medication. Side effects are usually local reactions and mild.

Benefits to patients include free progesterone medications as well as a $1,500 (INR 72,000) honorarium for participating and completing the study questionnaires.

Participating patients will be IVF candidates, including those undergoing ICSI, Blastocyst and PGD, who are age 18-42 who have had less than three prior IVF cycles and an FSH less than 15IU/L and estradiol less than 80 pg/mL. Other exclusion criteria exist.

Folate receptor blockade may compromise fertility

Treatment of impaired folate metabolism caused by an autoimmune response might improve the chances of conception among certain women with fertility problems, research suggests.

Michelle Murphy (Universitat Rovira i Virgili, Reus, Spain) and colleagues report women who tested positive for folate receptor (FR)-blocking autoantibodies were 12 times more likely to have fertility problems than those testing negative.

Observing that folate cell delivery is important in reproductive processes, the team tested for the presence of FR-blocking autoantibodies in repeated blood samples collected 10–12 weeks apart from 17 women who had failed to conceive during 12 menstrual cycles and 25 controls who had experienced a normal conception and pregnancy outcome.

Overall, five (29 percent) women with subfertility had at least one positive FR-blocking autoantibody titer, compared with just one (4 percent) women in the control group. Statistical analysis confirmed that testing positive for FR-blocking autoantibodies was a significant risk factor for subfertility (odds ratio = 12).

“Further investigation is required to understand the nature of the association between FR autoimmunity and subfertility and the potential benefits of using immune suppressants, corticosteroids, and high-dose folic acid in this disorder,” the researchers propose.


Source: Fertility and Sterility 2008; Advance online publication

Study fails to find link between fertility treatment and breast cancer

Fertility treatment does not increase a woman's risk of developing breast cancer, according to a study of more than 25,000 women with fertility problems in the Netherlands.

The study will help to reassure patients concerned that the powerful doses of hormones that are part of fertility treatment might put them at risk of developing cancer in the future.

At the beginning of an IVF treatment cycle, women are given a course of hormone drugs to stimulate their ovaries to produce more eggs than usual so that clinicians can produce several fertilised embryos in vitro.

The treatment causes large spikes in oestrogen levels in the body. In theory this could promote the development of breast cancer, which is sensitive to the hormone.

The Dutch study, carried out by Dr Alexandra van den Belt-Dousebout at the Netherlands Cancer Institute in Amsterdam, examined patient records from all 12 IVF clinics in the country between 1980 and 1995.

Her team compared 18,970 women who had had at least one cycle of IVF treatment and 7,536 other women with fertility problems who had not received fertility treatment. They matched these patients to records in the National Cancer Registry to establish whether they had gone on to develop breast cancer.

Of the 378 women who developed breast cancer, 266 were in the IVF group and 112 were in the non-IVF group. After adjusting for known risk factors such as age, the number of children the women already had, the age they began menstruating, family history of breast cancer and body mass index, the team found no statistical difference between the two groups, suggesting that IVF treatment does not increase a woman's chances of developing breast cancer.

Van den Belt-Dousebout presented her results at the American Society for Reproductive Medicine in San Francisco.

"From 10 years after treatment breast cancer risk was moderately increased in the IVF group but also in the non-IVF group, compared to the general population," van den Belt-Dousebout and her colleagues wrote in their presentation, "This may be explained by a lower number of children compared to the general population."

Having children is known to reduce the risk of breast cancer in women.

Oocyte electroactivation after ICSI

Electrical activation of oocytes after ICSI can significantly improve the fertilization rate in selected patients, according to the results of a randomized controlled study.

Specialists from the Egyptian IVF-ET Center in Cairo, Egypt, conducted the study to estimate the effect of electrical activation of oocytes in patients with previously failed or limited fertilization after ICSI, and in patients likely to have failed fertilization due to teratozoospermia.

Previous research has suggested that fertilization failure occurs in an estimated 2-3 percent of ICSI cycles and is often due to the failure of oocyte activation. Past studies have provided some evidence to suggest that electrical activation (or electroactivation) of oocytes can improve success rates.

The researchers studied the effect of electrical activation in 241 ICSI cycles involving couples with severe oligoasthenospermia or azoospermia. Poor or failed fertilization was expected in these cycles because of 100 percent abnormal sperm morphology or totally immotile sperm. In all cases the female partner was under 40 years of age and had a normal hormonal profile and no pelvic pathology.

The oocytes from each patient were randomly assigned on a one-to-one basis to either electroactivation (n = 1,640) or no electroactivation (n = 1,435). Electroactivation was performed 30 minutes after ICSI, using a double-square direct current pulse, and embryo transfer was performed with the best available embryos.

The researchers (Mansour R et al) present their findings in a new paper due to be published in the journal Fertility and Sterility. They report that:

The fertilization rate was significantly higher in the electroactivation group, compared with the control group: 68 percent versus 60 percent respectively (odds ratio 1.40; 95 percent confidence interval 1.20-1.63).
There was no significant difference between the two groups in the oocyte degeneration rate (5.9 percent in the electroactivation group and 4.9 percent in the control group).
There were a total of 112 clinical pregnancies in the study. In 15 of these, the embryos transferred were derived solely from the electroactivated group (out of a total of 34 embryo transfer procedures involving such embryos – a clinical pregnancy rate of 44 percent). In 69 of the clinical pregnancies the embryos transferred were derived solely from the control group (out of a total of 69 embryo transfer procedures involving such embryos – a clinical pregnancy rate of 48 percent). In the remaining 64, the embryos transferred were derived from both groups (out of a total of 138 embryo transfer procedures – a clinical pregnancy rate of 46.4 percent).
The miscarriage rates were: 20 percent (3 out of 15 clinical pregnancies) when the embryos transferred were derived solely from the electroactivated group, 9 per cent (3 out of 33 clinical pregnancies) when the embryos transferred were derived solely from the control group, and 9.4 percent (6 out of 64 clinical pregnancies) when the embryos transferred were derived from both groups.
Total fertilization failure did not occur in the study group, but occurred in five cycles in the control group.
Concluding, the researchers write that electroactivation of oocytes after ICSI can significantly improve the chances of fertilization, but stress: “However, more studies are needed to evaluate the clinical significance and safety of this technique.

“It is recommended in cases of previous failure of fertilization or limited fertilization, as well as in cases of severe oligoasthenospermia or azoospermia with 100 percent abnormal forms or zero motility.”

Source: Fertility and Sterility 2008;in press

Engrish

Catty Humor

Relationships Today

Cartoon of the Week

No Smoking

Top 10 Bush-isms

mApple Store

Exotic Pets: A No No

Gold Porsche

This 22-karat gold-plated Boxster goes by the name of Gold Porsche.

There will be limited production of models for sale (nine worldwide).

However, if you've got the cash (and a real burning desire to ensure everyone knows you've got some), any Porsche model, regardless of engine configuration or interior, can be covered in the beaten gold.

As a buyer, you can choose which of the vehicle's parts to goldenize (the body, the steering wheel, the doorknobs, the wheels and so on).

For the smallest Boxster, pricing starts at around 150,000 Euros (around $190,000 U.S.).

No word on how much heavier the Porsche gets with the flash, but we're sure it's worth its weight in gold

Autorickshaw to Lavasa

We must get beyond textbooks, go out into the bypaths... and tell the world the glories of our journey.
-John Hope Franklin

An auto rickshaw or tuk tuk (auto, rick, autorick or rickshaw in popular parlance) is a motor vehicle that is one of the chief modes of transport across many parts of South and East Asia, especially as a vehicle for hire. It is a motorized version of the traditional rickshaw or velotaxi, a small three-wheeled cart driven by a person, and is related to the cabin cycle. Auto rickshaws are particularly popular where traffic congestion is a problem and is most preferred by the cost-conscious developing economies. They are common in many Asian cities like Bangkok, Pune, Delhi, Mumbai, Hyderabad , and Bangalore, and some can be seen on the streets of China Town in London. Auto rickshaws are often portrayed in Indian films (Auto Shankar, Basha, Aye Auto, Oram Po) as well as some Hollywood and foreign productions such as the James Bond film Octopussy and the Canada-India film Amal. Auto rickshaws are also prominent in the fuel-poor London of 2027 A.D. depicted in Children of Men. A memorable tuk-tuk chase features in the Thai film Ong-Bak: Muay Thai Warrior, climaxing with many of them driving off the edge of an unfinished elevated expressway. James Bond (Pierce Brosnan) rides in a tuk-tuk in a Visa Card commercial seen here!

And why am I talking about autorickshaws today? Because I just discovered a new land-route to Lavasa via our humble autorickshaw(see photos).I chased the autorickshaw for almost a Km and realized that it was ascending the ghats with a 8-pax load effortlessly. Eureka - another way to reach the Land of Zeus! If you reach Pirangut at the foothills of the Sahyadri(which is amply connected to Pune), you could take an autorickshaw to Lavasa:)))

A few days ago I walked along the edge of the lake and was treated to the crunch and rustle of leaves with each step I made. The acoustics of this season are different and all sounds, no matter how hushed, are as crisp as autumn air.
-Eric Sloane

The colors of Lavasa change every month. The township is growing day & night. There are over 12,000 workers giving it all they have 7 x 24! The predominant color now is rust, which goes very well with the red earth color of the terrain. The Warasgaon lake is shrinking at a rapid pace throwing up swathes of red earth giving dramatic pictures.The shrubbery is dry & literally crackles under your feet. The very much remembered Eric Sloanes lines as above with every step I took. The lake is like a picture post-card now, with migratory birds in droves sitting on the branches of an inaccessible part of the outer boundaries of the Dasave lake. The multicolored flowers complement the rusty dried bush all around. It is as if a life cycle of Nature is in active motion all around... new life blooming and old life getting recycled into the red earth."Ashes to ashes, dust to dust" -- A phrase from the English burial service, used sometimes to denote total finality. It is based on scriptural texts such as 'Dust thou art, and unto dust thou shalt return' (Genesis 3:19), and 'I will bring thee to ashes upon the earth in the sight of all them that behold thee' (Ezekiel 27:18). Physically, we are made of chemicals - a carbon based life-form, so we come from the earth and when we die, we re-enter the carbon cycle. for our lifetimes we have a consciousness and many would say a spirit/soul as well as the use of atoms from planet earth - on death, our mortal remains naturally return our chemicals to the earth/system. The Bible and the burial service both reflect the transient state of human life in those words....I think the same goes for the Nature around us.. ditto for the flowers & the shrubs & the trees of Lavasa....

Let me now tell you about the first love of my life - the seas.....

Many's the night I spent with Minnie the Mermaid, Down at the bottom of the sea.
There among the corals,
That's where I lost my morals,
Gee but she was good to me, oh, oh, oh,
Ashes to ashes and dust to dust,
Two twin beds and only one of them mussed ...

It goes on from there for a bit.

-Anonymous

At Lavasa, it is the huge expanses of sweet-water that are the love-of-my-life. And then I glided on the waters of both the lakes - The Dasave Lake on a Pontoon Boat & the Warasgaon Lake on an Inflatable search-and-rescue dingy with a fast Mercury outboard motor! We darted over the waves at around 60 kms/hour, skimmed the water in chilling curves and zoomed into the rising sun at 6:30am! They have the water “scooters”, the sea “Vespas”. No licence is required and it is so easy to ride them that not even a course is necessary. In case of fall, nothing to fear: a device turns off the engine and the vehicle remains standing in order to enable its passenger to climb up and start again.Cedwin & his team have started the marina activities only on December 01, 2008 & have already kicked up the expectations sky-high! For the more athletic ones you can try water skiing; those who do not have a weak heart can experience the thrill of paraflying, that is flying with a paraglider following a motorboat; those who only want to have fun in groups can try the pontoon boats or the crazy-squirty-bumper-boats. A pontoon is a flat-bottomed boat simply constructed from closed cylinders such as pipes or barrels creating a raft (See video). Pontoon boats generally are low cost and less expensive to insure than a normal boat, even when equipped with engines of over 200hp. They are also almost foolproof to operate and cannot be sunk. Their shallow draft also reduces damage from submerge collisions and being run aground. Pontoon boats are also used as small vehicle ferries to cross rivers and lakes in many parts of the world, especially in Africa. Pontoon ferries may be motorised, such as the Kazungula Ferry across the Zambezi River, or powered by another boat, or pulled by cables. A type of ferry known as the cable ferry (called 'punts' in Australia and New Zealand) pull themselves across a river using a motor or human power applied to the cable, which also guides the pontoon. In the rural town of Richmond, MN, a farmer called Ambrose Weeres had an idea that if you put a wooden deck on top of two columns of steel barrels welded together end to end, you would have a sturdy deck that would be more stable on a lake than a conventional boat. This proved to be right.

Being in the land of 10,000 lakes, Ambrose thought this idea might have some potential to be marketed. He started out building a few boats and sold them with the help of select dealers. He needed a name for his first pontoon and he couldn't think of a better name than "The Empress", because of what it started. He never knew how popular these boats would be. Some time later, Ambrose was labeled "Mr. Pontoon" for his invention of the pontoon boat and was elected to the Minnesota Marina Hall of Fame for his accomplishments.India has imported its first Pontoon Boat for the Dasave Lake Family Cruises. You can hardly hear the silent petrol engine that takes the Pontoons effortlessly across the lake. you could have cocktail dinners on the Pontoons & would not spill a drop from a full glass of your favorite cocktail. Cheers!!!!

We wander for distraction, but we travel for fulfillment. ~Hilaire Belloc