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Study Demonstrates Superiority of ICSI over IVF Procedure in Extremely Low Ooocyte Retrieval Cycles

Intracytoplasmic sperm injection (ICSI), in contrast to the conventional IVF procedures, may help attain a higher rate of normal fertilization in extremely low oocyte retrieval cycles. The results of the study have been published in the recent issue of the journal Fertility and Sterility. Yu-Che Ou from the Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taiwan, and colleagues, conducted a case-control study on infertile subjects with one to three oocytes per retrieval, and were divided into two groups undergoing either ICSI or IVF treatment. During the study, the cycle cancellation, fertilization, implantation and clinical pregnancy rates per transfer were observed. The study results are shown in the Table:

Although the rates of clinical pregnancy, implantation, and live births per transfer were higher in the ICSI group, the difference was not statistically significant between the two groups. Also, the cycle cancellation and complete fertilization failure rates were found to be similar in both the groups.Earlier, Requena, et al. (Journal of Assisted Reproduction and Genetics, 2000) conducted a prospective case-control study to evaluate maturation in vitro of human oocytes (MIVHO) as an alternate to IVF treatment, in low ovarian responders. Oocyte retrieval, maturation in vitro, fertilization, and blastocyst development rates were observed in spontaneously ovulatory women at the Instituto Valenciano de Infertilidad. The study results showed that the oocyte retrieval rate was considerably higher in cases where the pickup was carried out before follicular selection. The results of MIVHO in normal responders as well as low responders with an ovarian content of early antral follicles >5, were comparable. The study results demonstrated that MIVHO in low responders with an adequate number of early antral follicles could be successful and oocyte retrieval before follicular selection would aid in attaining more oocytes.

Although low ovarian response is not well defined, usually a patient with <34 oocytes, serum peak levels of <500mg/ml after aggressive stimulation, and with a background of at least two unsuccessful attempts of ovarian stimulation, is considered to be a low responder. Low ovarian reserve could be a result of high body mass index, pelvic adhesions, prior ovarian surgery, or progressive age. As the IVF outcome is directly dependent on the number of embryos available, low embryo count could result in decreased pregnancy rates.Though ICSI is associated with damage to a low percentage of injected oocytes, this micro-assisted fertilization technique is preferable in cases of oligospermia and azoospermia. Demonstrating the better performance of ICSI compared to IVF in very low oocyte retrieval cycles, the current study suggests ICSI as a superior choice for treating this condition.

References
1. Ou YC, Lan KC, Huang FJ, Kung FT, Lan TH, Chang SY. Comparison of in vitro fertilization versus intracytoplasmic sperm injection in extremely low oocyte retrieval cycles. Fertil Steril. 2008 Dec 22. [Epub ahead of print].
2. Requena A, Neuspiller F, Cobo AC, et al. The potential use of maturation in vitro of human oocytes in low responder patients. J Assist Reprod Genet. 2000 May;17(5):239-44

New Research Questions Use Of Common Fertility Treatments

A new study published on bmj.com has found that fertility is not improved in infertile couples who have been treated with long-established medical interventions. The team of researchers led by the University of Aberdeen has called for UK and national guidelines to be reviewed with this new evidence that challenges current practices.

In the UK, one in seven couples experience infertility. Of these, about 25% of the infertility is unexplained, and the standard treatment includes a body of common interventions that have been used for years and have been issued by the National Institute for Health and Clinical Excellence (NICE).

The research team set out to compare two specific interventions with expectant management (i.e., no treatment). From four teaching hospitals and a district general hospital in Scotland, they recruited a sample of 580 women who have had unexplained infertility for over two years. The women were randomly assigned such that one group had no medical intervention and tried naturally to become pregnant, a second group took oral clomifene citrate (CC) to correct subtle ovulatory dysfunction, and a third group received unstimulated intra-uterine insemination (IUI) of sperm.

During the course of the study, 101 women became pregnant and had a live birth. The birth rate for women with no intervention was 17%, and the rates for the oral CC group and the IUI group were 14% and 23%, respectively. According to the researchers, the 6% difference between the IUI and the non-intervention group is no large enough for the results to suggest a meaningful and significant improvement in the live birth rate.

Many women suffered from side effects that included: pain, bloating, hot flushes, nausea and headaches. These affected about 10 to 20% of women, most of whom were taking oral CC. Also, it is worth noting that satisfaction was higher in the groups of women being actively treated - as they were reassured by the treatment process - compared to women who received no intervention.

"These interventions, which have been in use for many years, are unlikely to be more effective than no treatment. These results challenge current practice, as endorsed by a national guideline in the UK," conclude the authors.

Tarek El-Toukhy and Yacoub Khalaf (Assisted Conception Unit at Guy's and St Thomas' NHS Foundation Trust) write in an accompanying editorial that: "As a direct result of the lack of evidence, many couples with unexplained infertility endure (and even request) expensive, potentially hazardous, and often unnecessary treatments." There is a need for high quality clinical trials as well as better information for patients to determine the best treatments in light of effectiveness and adverse effects. El-Toukhy and Khalaf also call for the current NICE guidelines to be reviewed with this research in mind.

Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial
S Bhattacharya, K Harrild, J Mollison, S Wordsworth, C Tay, A Harrold, D McQueen, H Lyall, L Johnston, J Burrage, S Grossett, H Walton, J Lynch, A Johnstone, S Kini, A Raja, A Templeton
BMJ (2008). 337: a716.
doi:10.1136/bmj.a716

Study Links Water Pollution With Declining Male Fertility

New research strengthens the link between water pollution and rising male fertility problems. The study, by Brunel University, the Universities of Exeter and Reading and the Centre for Ecology & Hydrology, shows for the first time how a group of testosterone-blocking chemicals is finding its way into UK rivers, affecting wildlife and potentially humans. The research was supported by the Natural Environment Research Council and is now published in the journal Environmental Health Perspectives

The study identified a new group of chemicals that act as 'anti-androgens'. This means that they inhibit the function of the male hormone, testosterone, reducing male fertility. Some of these are contained in medicines, including cancer treatments, pharmaceutical treatments, and pesticides used in agriculture. The research suggests that when they get into the water system, these chemicals may play a pivotal role in causing feminising effects in male fish.

Earlier research by Brunel University and the University of Exeter has shown how female sex hormones (estrogens), and chemicals that mimic estrogens, are leading to 'feminisation' of male fish. Found in some industrial chemicals and the contraceptive pill, they enter rivers via sewage treatment works. This causes reproductive problems by reducing fish breeding capability and in some cases can lead to male fish changing sex.

Other studies have also suggested that there may be a link between this phenomenon and the increase in human male fertility problems caused by testicular dysgenesis syndrome. Until now, this link lacked credence because the list of suspects causing effects in fish was limited to estrogenic chemicals whilst testicular dysgenesis is known to be caused by exposure to a range of anti-androgens.

Lead author on the research paper, Dr Susan Jobling at Brunel University's Institute for the Environment, said: "We have been working intensively in this field for over ten years. The new research findings illustrate the complexities in unravelling chemical causation of adverse health effects in wildlife populations and re-open the possibility of a human - wildlife connection in which effects seen in wild fish and in humans are caused by similar combinations of chemicals. We have identified a new group of chemicals in our study on fish, but do not know where they are coming from. A principal aim of our work is now to identify the source of these pollutants and work with regulators and relevant industry to test the effects of a mixture of these chemicals and the already known environmental estrogens and help protect environmental health."

Senior author, Professor Charles Tyler of the University of Exeter, said: "Our research shows that a much wider range of chemicals than we previously thought is leading to hormone disruption in fish. This means that the pollutants causing these problems are likely to be coming from a wide variety of sources. Our findings also strengthen the argument for the cocktail of chemicals in our water leading to hormone disruption in fish, and contributing to the rise in male reproductive problems. There are likely to be many reasons behind the rise in male fertility problems in humans, but these findings could reveal one, previously unknown, factor."

Bob Burn, Principal Statistician in the Statistical Services Centre at the University of Reading, said: "State-of-the-art statistical hierarchical modelling has allowed us to explore the complex associations between the exposure and potential effects seen in over 1000 fish sampled from 30 rivers in various parts of England."

The research took more than three years to complete and was conducted by the University of Exeter, Brunel University, University of Reading and the Centre for Ecology & Hydrology. Statistical modelling was supported by Beyond the Basics Ltd.

The research team is now focusing on identifying the source of anti-androgenic chemicals, as well as continuing to study their impact on reproductive health in wildlife and humans.

New Treatment For Common Cause Of Male Infertility

Researchers in Germany found that a simple and minimally invasive outpatient treatment for varicoceles, a common cause of male infertility that affects about 1 in 10 men, can significantly improve sperm function and pregnancy rates.

The study came from the University of Bonn Medical School and is published in the August issue of Radiology.

Lead author Dr Sebastian Flacke and colleagues found that the level of sperm motility present before having the treatment was also an important predictor of pregnancy success.

Flacke is now an associate professor of radiology at the Tufts University School of Medicine, director of noninvasive cardiovascular imaging and vice chair for research and development in the department of radiology at the Lahey Clinic in Burlington, Massachusetts.

He said that:

"Venous embolization, a simple treatment using a catheter through the groin, can help to improve sperm function in infertile men."

"With the patients' improved sperm function, more than one-quarter of their healthy partners were able to become pregnant," added Flacke.

Varicoceles is a condition like varicose veins where the blood vessels in the scrotum become tangled and swollen. Normally the blood flows from the testicles back to the heart via small veins that have a non-return valve to stop the blood flowing backwards to the testicles. But if these valves stop working, then the blood backs up, fails to leave the testicles properly and causes the vessels to bulge and swell.

Varicoceles is a common condition that generally has no symptoms or harmful side effects and affects between 10 and 15 per cent of adult men in the US. Figures from the National Institutes of Health suggest it mostly affects young men between 15 and 25. Occasionally the condition results in pain, shrinkage, or fertility problems.

Until recently, men with problematic varicoceles were treated with open surgery to remove the affected blood vessels, but now there is a minimally invasive procedure called catheter embolization which a man can have as an outpatient. Catheter embolization is where the radiologist inserts a small tube or catheter through a tiny cut in the groin, and using x-ray imaging, guides the catheter to the affected blood vessel and then blocks it using a platinum coil and a few millillitres of a liquid agent. The patient recovers quickly and is usually well enough to go back to work in 24 hours.

For this study, in order to identify what might affect pregnancy rates in couples where the man was infertile before undergoing varicocele embolization, Flacke and colleagues recruited 223 infertile men aged between 18 and 50 who had been diagnosed with at least one varicocele and who underwent embolization. All the men had healthy partners with whom they had been trying to conceive.

Before and after the procedure, all participants underwent a clinical exam (with ultrasound test), gave a semen specimen, and had their hormone levels tested.

The results showed that:226 of the patients' 228 varicoceles were successfully treated with embolization.

Follow up data was successfully obtained for 173 patients, and in these, three months after the procedure, the average sperm motility and sperm count was found to be significantly improved.

Six months later, 45 couples (26 per cent of the 173 followed up), reported a pregnancy.

The only significant pre-treatment predictor of post-treatment pregnancy success was sperm motility.

Other measures such as hormone levels, clinical grading of varicoceles, Doppler ultrasound findings, and other semen parameters did not reach statistical significance.
Flacke said:

"Embolization of varicoceles in infertile men may be considered a useful adjunct to in-vitro fertilization."

"Embolization of Varicocles: Pretreatment Sperm Motility Predicts Later Pregnancy in Partners of Infertile Men."
Sebastian Flacke, Michael Schuster, Attila Kovacs, Marcus von Falkenhausen, Holger M. Strunk, Gerhard Haidl, and Hans H. Schild.
Radiology 2008 248: 540-549.
Volume 248, Issue 2, August 2008
DOI: 10.1148/radiol.2482071675.

Singapore Airlines

A mother and her young inquisitive son were flying Singapore
Airlines from Singapore to New York.

The son (who had been looking out the window) turned to his mother
and asked, "If dogs have baby dogs and cats have baby cats, why
don't planes have baby planes?"

The mother (who couldn't think of an answer) told her son to ask the
pretty flight attendant.
So the boy dutifully asked the flight attendant, "If dogs have baby
dogs and cats have baby cats, why don't planes have baby planes?"

The flight attendant asked, "Did your mother tell you to ask me
that?" The little boy admitted that she did.

"Well, then, tell your mother that there are no baby planes because
Singapore Airlines always pulls out on time. Now, let your mother
explain that to you!!!"

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