Thursday, 9 January 2014

Scrotal heating and sedentary position

Testicular descent into the scrotum normally occurs by birth in boys and failure of testicular descent, especially when this extends into puberty and adulthood, results in absence of spermatogenesis. The testes descend into the scrotum in order that their temperature can be kept 3–4°C below core body temperature, as maintenance at normal body temperature is incompatible with spermatogenesis. It is probably also important that the testes are descended into the bottom of the scrotum rather than being placed at the top where their proximity to the body surface is likely to impair cooling of the testis. This is mentioned because it is reckoned that failure of the testes to descend into the bottom of the scrotum should probably be classified as a form of cryptorchidism . As well as testis position, the two other key elements in ensuring cooling of the testis are the presence of a vascular-rich corrugated scrotal surface via which heat loss can occur and the presence of an arterio-venous plexus (the pampiniform plexus) in the spermatic cord and which functions as a heat exchanger to cool incoming blood to the testis by heat exchange with the cooler venous blood that is exiting the testis . Normal functioning of this plexus is important for maintaining testicular coolness, and it is potentially susceptible to disruption by chemicals or by vascular-active drugs disorders such as varicocele in which the veins in the plexus are varicosed . However, even if the pampiniform plexus is functioning normally, it cannot cool the incoming arterial blood to the testis unless the blood leaving the testis is already itself cool, and this requires heat loss via the scrotal surface and its transmission to the underlying testes. Therefore, anything that impedes scrotal heat loss will affect testicular temperature and in turn any elevation of testicular temperature will have a harmful effect on spermatogenesis. In general, the more prolonged is the elevation in testicular temperature, then the greater will be the detrimental effect on spermatogenesis 
 
The most obvious things that can affect scrotal heat loss are a febrile illness such as influenza, exposure to an exogenous heat source, such as occupationally (bakers, welders, foundry workers) or via taking a hot bath . Based on experimental studies in laboratory animals, a 30 min soak in a moderately hot bath (40–42°C) impairs spermatogenesis  and, more importantly, it can induce germ cell apoptosis, DNA damage to the sperm and impair embryo development and fertility when ‘affected’ males are mated with normal females (Paul et al. 2008a,b). Follow-up studies have provided insight into the mechanisms involved (Paul et al. 2009). These have shown that heat exposure causes hypoxia and oxidative stress responses in the germ cells, manifest as increased expression of hypoxia inducible factor 1α, haem oxygenase 1, glutathione peroxidase 1 and glutathione-S-transferase-α, which push the germ cells towards apoptosis (Paul et al. 2009). Perhaps of more concern is if mild oxidative DNA damage is induced such that the germ cells continue their development into sperm, as this is associated with increased time for such sperm to initiate a pregnancy in humans (Loft et al. 2003). The adverse effects of scrotal heating on spermatogenesis and fertility are equally evident in non-human primates (Lue et al. 2002). Exposure to heat in other situations, such as in a hot shower, would have minimal effect as the scrotum is still able to thermo-regulate (it is not immersed in water) and a similar situation applies to saunas, although spending a long time in very hot saunas is detrimental.
 
Arguably of more concern are lifestyle and occupational factors that cause men to spend a long time in a sedentary position, something that has become common for many men working in Western countries today (figure 2). When seated, air does not circulate so easily around the scrotum and therefore there is less-efficient cooling, an effect likely to be exacerbated if wearing tight underpants or trousers. In studies of men in whom scrotal temperature was measured continuously in relation to position and activity, scrotal temperature increased progressively with duration of sedentation, and this was associated with lower sperm counts (Hjollund et al. 2000, 2002a,b). Studies in lorry and taxi drivers, who spend a long time seated, have also produced evidence for detrimental effects on semen quality (Figa-Talamanca et al. 1996; Bujan et al. 2000). However, overall, the relationship between time spent seated and poor semen quality is not suggestive of a major impact on fertility (Hjollund et al. 2000, 2002b;Stoy et al. 2004). Other studies have investigated the impact of wearing tight versus loose underwear and reached similar conclusions (Mieusset & Bujan 1995b). The most recent scenario investigated has been the impact on scrotal temperature of using a laptop computer (Sheynkin et al. 2005). It is perhaps more likely that scrotal heating may combine with or exacerbate adverse effects of other environmental/lifestyle factors and that only then will there be a significant impact on fertility (Lue et al. 2000).
 
Scrotal heating has been investigated as a potential contraceptive method in men and shown to be effective (Mieusset & Bujan 1995a). However, other studies that have tried to link more modest elevations in scrotal temperature (such as those associated with sedentary position) to infertility have not shown major or consistent associations, as outlined above. Nevertheless, it is common sense that any factor that impedes normal cooling of the scrotum/testes can only have an adverse effect on spermatogenesis, and it is therefore prudent to advise all men who are attempting to father a pregnancy, especially if they are known to have low sperm counts or low sperm motility, to take steps to minimize scrotal heating by any of the pathways mentioned above—where this has been done in a controlled way, the results have been positive (Jung et al. 2001). Such small lifestyle changes can only have a beneficial effect on spermatogenesis.

Wednesday, 8 January 2014

New Method to Detect Genetic defects in Egg cells could Double Success Rate of IVF


Infertility affects up to 15 percent of couples around the world, and in virto fertilization (IVF) is one way to treat this common condition. A study published by cell press December 19th in the journal cell reveals a safe, accurate, and low-cost thereby increase a couple’s chance of producing a healthy child.
Through whole-genome sequencing of individual egg cells, the new method detects chromosomal abnormalities and DNA sequence variations associated with genetic disorders. “In the way, we kill two birds with one stone: one setoff deep sequencing analysis to avid two types of genetic problem,” says study author Jie Qiao of Third Hospital, Peking University. “Theoretically, if this works perfectly, we will be able to double the success rate of test tube baby technology from 30 percent to 60 percent or even more.”
The IVF procedure involves joining a woman’s egg and a man’s sperm in a laboratory dish and then transferring embryos into the woman’s womb. Various procedures are currently available to detect genetic defects in embryos prior to implantation, but these approaches are often invasive, requiring the removal of cells from the growing embryo,  and do not simultaneously detect both chromosomal abnormalities and DNA sequence  variations associated with genetic disorders.
Researchers have recently developed whole-genome sequencing methods too simultaneously detect both types of defects in single human sperm cells, but until now, an analogous approach had not been applied to egg cells even though chromosomal abnormalities are much more common in egg cells than in sperm cells.
In the new study, Sunney Xie of Peking University and Harvard University teamed up with Qiao and Fuchou Tang of Peking University to develop a method for sequencing the entire genomes of polar bodies – cells that arise as a byproduct of egg cell division and often die later on.
Because polar bodies are dispensable for human embryonic development, they can be safety removed without harming the embryo. “We are now starting a clinical trial based on this approach,” Xie says.  “If the clinical trial works, this technique could enormously increase the success rate of IVF, especially for older women or women who have had recurrent  miscarriages.”

First of all, I will take a big breath and be happy that I have made it to 30 weeks. Yeah!

I can’t believe I’ve already been here in Genesis for two weeks, they are the biggest savior of my life and obviously friends Nidhi and Shruti, and husband Sandeep. I just can’t express enough gratitude for Genesis and their care. Visits from my loved ones, their texts, e-mails, calls, and bouquets, I would like to thank them for keeping me sane and not letting me psyched.

My immediate goal is to stay pregnant until Sandeep is back in town, although my mum is here, but I wish he should look me at my full bloom phase. Genesis has given me the confidence and I believe everything will be fine. I am taking good care of myself.

This picture of mine, Sandeep says: “What a Show”
Honestly, this phase is the most phenomenal experience a woman can have. I would like to bless and Genesis for giving Sandeep, and me a chance to live again, for giving us hope to become parents.

  • To be Mummy

PREPARING FOR AN IVF CYCLE AT GENESIS

The objective with In Vitro Fertilization is to expertly transfer one or two “competent” embryos to an optimal and receptive uterine environment and then hormonally support implantation. This requires a very individualized and meticulous approach to the evaluation and treatment of those factors that influence IVF outcome:

In 70-80% of cases, failed reproduction is a consequence of egg/embryo incompetence. The number of eggs a woman produces is influenced by her ovarian responsiveness to gonadotropin fertility drugs. This responsiveness in turn relates to her proximity to menopause. Ovarian responsiveness can be assessed by measuring FSH / estradiol (E2) and Inhibin B on the 3rd day of a prior menstrual cycle, and measuring AMH at any time in the cycle.  If the plasma FSH level measures greater than 9.0MIU/ml in association with plasma estradiol level of less than 70pg/ml by EIA, and/or the plasma inhibin B level is less than 45pg/ml, and AMH of less than 2.0ng/ml, it would suggest the possibility ofdiminishing ovarian reserve (DOR). This indicates a need to be more aggressive and strategic in the design of an individualized protocol used for controlled ovarian stimulation.

While the most important variable in IVF is structure and execution of the ovarian stimulation protocol, there is also little doubt that the quality of the IVF laboratory is also pivotal. However, in my experience, most reputable IVF programs have laboratory staff who are highly disciplined and efficient when it comes to structure and process, and are very capable of performing highly technical procedures such as intracytoplasmic sperm injection (ICSI), embryo biopsy, and assisted hatching (AH). In fact, poor IVF outcome results can usually be traced to clinical, rather than laboratory deficiencies. IVF procedures should only be performed by those who have the necessary experience and skill set, lest fertilization rates and embryo quality be severely compromised.

MY INSIGHT ON IVF

Over the past three years, I have met and consulted with hundreds of couples seeking treatment for diverse reproductive issues involving infertility and pregnancy loss. The universal thread that I have encountered is people’s hunger for information when they’re facing such situations. Many times, the response I get from patients after discussing their case in depth with them is “I wish I would have understood that before my first (or second) IVF cycle!”

Many people undertake fertility treatment with what they realize later to be very limited information on both their own diagnosis and what their treatment options are. I have created this blog to be, first and foremost, a source of meaningful and substantive information for those who are considering or currently undergoing fertility treatment. It is my wish that you’ll find something here that will give you additional insight, knowledge, and ultimately, hope.