Eggs From Heaven

After a night of drinking, Brian crept into bed beside his wife who was already asleep. He gave her a peck on the cheek and fell asleep. When he awoke he found a strange man standing at the end of his bed wearing a long flowing white robe.

"Who the hell are you?" demanded Brian, "and what are you doing in my bedroom?"

The mysterious Man answered, "This isn't your bedroom and I'm St. Peter".

Brian was stunned, "You mean I'm dead!!! That can't be, I have so much to live for, I haven't said goodbye to my family.... you've got to send me back right away".

St Peter replied, "Yes, you can be reincarnated but there is a catch. We can only send you back as a dog or a hen."

Brian was devastated, but knowing there was a farm not far from his house, he asked to be sent back as a hen. A flash of light later, he was covered in feathers and clucking around pecking the ground.

"This ain't so bad" he thought until he felt this strange feeling welling up inside him.

The farmyard rooster strolled over and said, "So you're the new hen, how are you enjoying your first day here?"

"It's not so bad," replies Brian, "but I have this strange feeling inside like I'm about to explode".

"You're ovulating," explained the rooster, "don't tell me you've never laid an egg before."

"Never," replies Brian. "Well just relax and let it happen."

And so he did, and after a few uncomfortable seconds later, an egg pops out from under his tail. An immense feeling of relief swept over him and his emotions got the better of him as he experienced motherhood for the first time. When he laid his second egg, the feeling of happiness was overwhelming and he knew that being reincarnated as a hen was the best thing that had happened to him..ever!!!

The joy kept coming and as he was just about to lay his third egg he felt an enormous smack on the back of his head and heard his wife shouting, "Brian, wake up you drunken bastard, you're shittin' in the bed."

Clomiphene Challenge Test

Women are born with their lifetime supply of eggs within the ovaries. Each month follicles, each of which contains one egg, are recruited under the influence of follicle stimulating hormone. One follicle will become dominant, develop to maturity, and be ovulated. Ovarian reserve is a measure of the “quality” of the eggs remaining within the ovaries. Ovarian
reserve naturally declines as a woman ages and approaches the menopause. However, diminished reserve can occur in younger women due to perimenopause, genetics, or for unknown reasons.
In the standard infertility evaluation, levels of the hormones FSH, LH, and estradiol are measured on day 3. An elevated FSH level on day 3 is one indication of poor ovarian reserve or that the menopause is approaching. The clomiphene citrate challenge test (CCCT) provides an additional assessment of ovarian reserve. The clomiphene citrate challenge test (CCCT) is a sensitive means to measure ovarian reserve and is often conducted if the FSH level is 10-15 mIU/mL or the E2 is >65 pg/mL. It is performed by measuring the day 3 FSH and estradiol levels, the patient takes 100 mg tablets of Clomiphene Citrate on cycle days 5-9, and her FSH is measured again on day 10. A poor CCCT test, regardless of patient age, indicates that there will be a decreased response to injectable medications in assisted reproductive technology cycles. Pregnancy success rates are lower in these women and there is an increased chance of miscarriage. The clomiphene citrate Challenge Test is routinely performed at our clinic in women aged 38 years or older regardless of how the cycle day 3 levels look. This will identify patients with incipient ovarian dysfunction. The clomiphene citrate challenge test should also be considered in women of any age with otherwise unexplained infertility as approximately 30% will show abnormalities that adversely impact their prognosis with fertility treatment.
A level from 10-12.5 mIU/mL predicts resistance to fertility medications and a diminished prognosis. At 12.5-15 mIU/mL, the prognosis is poor but pregnancies do occur with aggressive treatment. Levels greater than 15 mIU/mL indicate that infertility treatment with the patient’s own eggs is not likely to succeed and that egg donation should be offered. Patients with any FSH level greater than 10 mIU/mL should be referred to a fertility specialist for further evaluation. A poor clomiphene citrate challenge test indicates that it is unlikely that the couple will be successful using in vitro fertilization, IVF. Some clinics do not offer IVF to couples failing the CCCT test and others offer it but clearly explain the poor chance of success. Donor egg IVF is the best option for these couples.

A Cheaper Alternative To IVF

A landmark in the development of fertility treatment was announced by doctors yesterday with the birth of the first babies to be conceived using a revolutionary technique that offers a safer, cheaper alternative to IVF. The twin boy and girl, who were born on 18 October at the Radcliffe Infirmary in Oxford, were conceived using In Vitro Maturation (IVM), a method that dispenses with the use of costly fertility drugs, saving up to £1,500 (INR 120,000) on the normal price of treatment. The technique is also safer for the one in three women among those seeking fertility treatment who have polycystic ovaries, a condition that puts them at high risk of dangerous side effects from fertility drugs. Specialists said the development could make in vitro techniques available to more infertile couples by cutting the cost of treatment. Infertility is estimated to affect one in six couples in the UK but IVF costs around £5,000 (INR 400,000) a cycle and treatment is restricted on the NHS!

Tim Child, a consultant gynaecologist at the Oxford Fertility Clinic and senior fellow in reproductive medicine at Oxford University, who led the work, said: "I think it is a safer, cheaper alternative to IVF for all women. However, for many women the success rates are currently much lower. Research in the future will address this." The Oxford Fertility Clinic is the only one in the UK licensed to use the technique: 20 cycles of treatment have been carried out and four other women are currently pregnant, giving a pregnancy rate of 25 per cent. This is expected to improve with further experience. In addition, without the need for drugs, repeating the procedure would be less taxing on the woman. For standard IVF, the Oxford clinic's pregnancy rate is 45 per cent.

The parents of the babies, who have asked to remain anonymous, were delighted, Mr Child said. At birth the boy, born first, weighed 6lb 11oz and the girl weighed 5lb 14oz. "The parents are ecstatic. They have got absolutely stunning twins. They went home on Tuesday to start their new life together. It is wonderful."

In standard IVF, the woman takes fertility drugs for five weeks to stimulate production of her eggs, which are then collected direct from her ovaries under the guidance of ultrasound, before being fertilised in the laboratory. The drugs cost between £600 and £1,500, with charges often higher in London. The procedure is time consuming and uncomfortable and for the third of women with polycystic ovaries there is a one in 10 risk of severe ovarian hyperstimulation syndrome, a dangerous side-effect that in rare cases can prove fatal.

IVM avoids the use of drugs and instead involves collecting eggs from the ovaries while they are still immature. The eggs are then grown in the laboratory for 24 to 48 hours before being fertilised and replaced in the womb. The technique was pioneered by the University of McGill in Montreal, Canada, where Mr Child spent two years researching and developing it before joining the University of Oxford in 2004. It has also been used in Seoul, South Korea, and Scandinavia. To date about 400 babies have been born worldwide using IVM compared with around two million by IVF. At present the Oxford Fertility Clinic is only offering the treatment to women with polycystic ovaries, but in the long term Mr Child said he hoped to offer the procedure to all women. "When we see patients we say these are the options and it is up to them to decide. We are not offering it to women with normal ovaries at present because we don't get enough eggs from them. It depends on the number of resting follicles and with normal ovaries you don't get so many.

"On average we get four eggs from a woman with normal ovaries compared with 16 from one with polycystic ovaries. The procedure involves a process of attrition – two-thirds mature and two-thirds of those fertilise – so you need a decent number to start with." Research on developing the culture medium in which the eggs are matured in the laboratory could reduce the attrition rate so that fewer eggs are needed. The technique could then become suitable for women with normal ovaries, Mr Child said.

A second drawback of the procedure was that eggs grown in culture had a harder outer shell than those matured in the ovary and were more difficult for sperm to penetrate. The eggs had to be fertilised by ICSI – injecting a single sperm directly into the egg. "We hope to develop the culture medium so the egg doesn't mind being grown in the laboratory and we can use ordinary insemination [mixing eggs and sperm so fertilisation occurs naturally]. But in most IVF clinics, 50 per cent of patients are treated with ICSI anyway," he said. "Anything that reduces the cost of IVF, provided it is safe, means treatment could be available to more people. But this is an emerging technology – it is very early days. The most important thing is that patients get proper information so that they can make a decision on what is best for themselves."

Embryo Biopsy

Since the birth of the first baby achieved through conception outside of the human body in 1978, the principles of "in vitro" fertilization and culture have remained the same - careful establishment and maintenance of a well-controlled, sterile environment in which the normal physiology of fertilization and early development can be played out relatively undisturbed to provide healthy embryos for transfer back into the body. During the ensuing two decades, much has been learned, however, about the tolerances of such a system and how this technique can be exploited to treat a widening range of infertility cases. There have been great strides made in development of more appropriate culture media that has enabled embryos to be grown for extended periods of time in culture. Surplus embryos and possibly eggs may now routinely be cryopreserved in liquid nitrogen for use in subsequent attempts at pregnancy. Fertilization itself is no longer a hit-and-miss affair with the advent of assisted fertilization through micromanipulation. Embryos can be micro-manipulated for cell biopsy to determine their genetic status as well as aid in their ability to implant through drilling into their outer shell (assisted hatching). Embryo Biopsy is performed for preimplantation genetic diagnosis (PGD) and enables the screening of both the unfertilized egg by removal of the first polar body, or the fertilized multi-cellular embryo by removal of one or more cells either at the 6-12 cell stage(see picture) or from the trophectoderm of the blastocyst. This material can be probed for both genetic mutations or gross chromosomal errors. This technology remains in its infancy and can be of profound importance clinically, but at this time only for cases with very clear medically-defined needs. The biopsy procedure requires very exacting skills of the IVF laboratory, and the egg or embryo is not entirely free of risk during the procedure. Hence, couples whose offspring have a high chance of inheriting a genetic disorder may have their embryos screened. Women who are at risk of generating eggs with a high risk of chromosomal anomalies can benefit from having their eggs or embryos screened for chromosomal normality.

Risks Associated With Fertility Medications

The controlled "superovulation" techniques used in IVF are designed to stimulate the ovaries to produce several eggs (oocytes) rather than the usual single egg as in a natural cycle. Multiple eggs increase the potential availability of multiple embryos (fertilized eggs) for transfer and ultimately increase the probability of conception. The medications required to boost egg production may include, but are not limited to the following: Lupride/Gonapeptyl (gonadotropin releasing hormone-agonist), Antagon or Cetrotide (gonadotropin releasing hormone-antagonist), Menopur, Bravelle or Gonal-F (FSH, follicle stimulating hormone), GMH(combination of FSH and LH, luteinizing hormone), and Choragon or Ovidrel(hCG, human chorionic gonadotropin). Each is administered by injection only. Most medications are given subcutaneously (beneath the skin), though some are intramuscular injections (into the muscle). Risks associated with injectable fertility medications may include but are not limited to, tenderness, infection, hematoma, and swelling or bruising at the injection site. Risks associated with the medications may include, but are not limited to, allergic reactions, hyperstimulation of the ovaries (mild, moderate or severe), failure of the ovaries to respond and cancellation of the treatment cycle.

There are situations that can occur during a stimulation that may necessitate canceling your IVF cycle and stopping treatment for a period of time. This occurs because the ovaries produce either too many or too few eggs in response to drug stimulation protocol. Although we realize that this can be a big disappointment, at times it is necessary to discontinue the use of the medications to avoid the possibility of complications and to afford you the best chance of future success. If canceling the cycle becomes necessary, you will be told to stop your injections. No hCG injection will be given and no egg retrieval will occur. You will be asked to schedule an appointment with your physician to make decisions regarding future treatment cycles.

When ovulation induction medications are used in fertility therapy, the ovaries are coaxed to produce more than one egg to the point of maturity. Consequently, hormone levels of estrogen and progesterone reach much higher than normal values. When the estrogen level becomes mildly to moderately elevated, side effects that may be experienced include, but are not limited to, fluid retention with slight transient weight gain, nausea, diarrhea, pelvic discomfort due to enlarged cystic ovaries, breast tenderness, mood swings, headache and fatigue.

If the estrogen level rises excessively and hCG is administered to trigger final maturation of the eggs, the following more serious complications may result:

Excessive fluid retention with fluid in the abdomen and/or chest cavity;
Thrombosis of arteries and/or veins (formation of blood clots) which may lead to stroke, embolus, or potentially fatal complications;
Abnormally enlarged ovaries, which have the possibility of rupturing or twisting (a surgical emergency)
Any of the three problems listed above may require prolonged hospitalization.

Given the potential for such severe complications, it is important that we carefully monitor the response to these medications. This monitoring also allows your physician to determine when the eggs are ready for the next stage, oocyte (egg) retrieval. Monitoring includes frequent blood drawing for estradiol (estrogen) and possibly progesterone, LH and FSH levels. These blood tests will take place over approximately a twelve-day period. Risks associated with blood drawing may include, but are not limited to:

Pain at the site of needle stick
Tenderness or infection of the skin
Bruising or scarring of the site of blood draw
Development of a blood clot in the vein (thrombosis, thrombophlebitis)

The second portion of the monitoring phase in IVF involves the use of intravaginal ultrasound to track follicular growth. The eggs develop inside fluid-filled cysts of the ovaries called follicles, which enlarge as the eggs mature. Ultrasound studies usually begin after an estrogen response has been measured and continue on a frequent basis until oocyte (egg) retrieval. The ultrasound studies are performed using a vaginal probe. Vaginal sonograms carry no appreciable risk but may cause slight discomfort, particularly as you near the point of ovulation.

Intracytoplasmic Sperm Injection (ICSI)

Through the controlled application of ovarian hyperstimulation, it is current practice to time the retrieval of mature oocytes (eggs) from a woman's ovary. The yield may vary anywhere from one to 30 or more eggs that may be retrieved depending on the responsiveness of the ovaries to the gonadotropins used to stimulate them. These eggs are gathered by the embryologist into an appropriately balanced salt solution and maintained at body temperature (37°C) until such time as they are ready to be inseminated. Meanwhile, a sample of semen containing the sperm destined to be used for each specific set of eggs is collected and processed by cell separation techniques to provide as clean and active a sample of sperm as possible. A major emphasis of the IVF laboratory is directed toward guaranteeing that the correct sperm go with the right eggs through good labeling and check systems. Ultimately, following several hours in culture, eggs and sperm can be mixed and allowed to bind and fertilize in a relatively natural fashion. Depending on the quality and maturity of both eggs and sperm, it is common for fertilization rates to vary considerably relative to the original number of eggs collected. Twenty eggs retrieved in no way guarantees 20 embryos. Likewise, 20 fertilized eggs in no way guarantees that there will be 20 embryos of sufficient quality for both cryopreservation and fresh transfer to the woman's body.

Central to the question of how many embryos are actually utilized in any IVF treatment cycle is the period during which the embryos are cultured in vitro. This can be as little as one day, or up to five in the case of blastocyst growth and transfer. Assuming that culture conditions are relatively optimal, there is less and less reason not to culture embryos throughout their pre-implantation stages to allow the embryos to "select" themselves for transfer or cryopreservation. The blastocyst is the term given to the very last stage of an embryo prior to it implanting into the endometrial lining of the uterus. The poorer the rates of blastocyst growth are, the more restricted the choice of embryo is at this stage of development. In any event, growth of any embryos to the blastocyst stage improves the level of discrimination of embryo viability available to the embryologist, and is key to reducing the numbers of embryos used for uterine transfer. The more confidence a clinic has in the viability of the embryos it transfers, the less need there is for multiple transfers of three or more embryos. Thus with the transfer of three or less embryos, the risk of multiple pregnancies is significantly reduced, in turn minimizing risks of pregnancy loss or fetal abnormalities common in multi-fetal pregnancies.

Micromanipulation is the technique whereby sperm, eggs and embryos can be handled on an inverted microscope stage, performing minute procedures at the microscopic level via joysticks that hydraulically operate glass microtools. Micro-manipulation first saw clinical use in IVF for purposes of assisted fertilization in the treatment of male factor infertility, where fertilization potential was low in cases of poor sperm quality. The ultimate evolution of this approach has been the development of the single sperm injection procedure referred to as Intracytoplasmic Sperm Injection, or ICSI. Sperm of virtually any quality and from any level of the male reproductive tract may be used with the only criterion for use being that the sperm is alive even if it is not moving (motile). Dead sperm may be able to achieve fertilization; however, the DNA or genetic material from such sperm is too degenerate to form a viable embryo. Immature sperm from the testicle or the epididymis can be retrieved for use with ICSI for men who possess no sperm in their ejaculated semen (azoospermia). This azoospermia is either due to an obstruction in the tract (obstructive), or to extremely low production of sperm in the testicle itself (non-obstructive). In certain cases, men may produce sufficient sperm, but they do not survive to the point of ejaculation (necrozoospermia). Consequently, instead of using non-viable sperm from the ejaculate, testicular biopsy will provide a ready source of freshly produced viable sperm.

With the almost unlimited potential to achieve some level of fertilization with ICSI regardless of sperm quality, it would seem that male factor infertility would no longer be of concern. It must be noted, however, that sub-fertility in men can be related to certain numerical and structural defects of the chromosomes and, therefore, there is a strong recommendation for all couples that achieve pregnancies from ICSI to undergo prenatal screening. In certain cases of obstructive azoospermia, there is a higher incidence of cystic fibrosis in the male. Hence, before embarking upon treatment of the more extreme forms of male factor infertility, it is advisable to have some cytogenetic screening performed. Incidentally, very subtle compromise in sperm quality may well be responsible for a marginally lower embryonic viability rate and a slightly higher early miscarriage rate even if such embryos implant. Such observations have led to the suggestion that the technique ICSI itself is at fault; but this misses the point that ICSI per se is not causing the problem, merely facilitating the use of sperm, which under other circumstances would never have even achieved fertilization.

The use of ICSI is now routinely applied to a range of clinical situations wherever there is a possibility that conventional in vitro fertilization may be suppressed or not occur. Such situations include the following: idiopathic or unexplained fertility; hyper-responsive ovarian stimulation cases where egg quality may be reduced; post-thaw sperm samples that survive poorly; post-thaw egg insemination; generation of embryos for pre-implantation genetic screening where embryos "clean" from any extraneous contaminating sperm is needed; or, indeed, any case where there is an extreme need to maximize normal fertilization, for example, when a woman has only a few eggs retrieved. It is possible to "rescue" cases following complete failed conventional fertilization with ICSI. The viability potential of these "late-fertilized" embryos is approximately half of timely fertilized embryos; nevertheless, they do generate successful live births. ICSI has become such a common feature of IVF therapy that it is fast becoming the insemination technique of choice.

Two Lawyers

Two lawyers had been life long friends: they were partners and shared everything , including their hot-blooded secretary . 

One day the secretary announced she was pregnant. They told her not to worry and assured her that they would pay all medical costs and would act as co-fathers when the child was born and provide all expenses thereafter. 

The day of delivery arrived. Both the lawyers were at the hospital pacing the floor in the waiting room. Finally one of them said, "I can't take this, I'm going down to sit in my car and wait there. Please come down and tell me as soon as the child is born!" 

The partner agreed to do that. About an hour later the partner approached the car with a very grave look on his face. 

"What happened ?" asked the waiting car occupant. 

The other partner announced, "They were twins and mine died!"