IVF and Infertility

Up to the blastocyst stage, the human embryo is surrounded by an outer most covering called the Zona pellucida. Prior to the implantation, the embryo has to escape from the Zona pellucida, a process known as hatching. Elasticity and thinning of the ZP are essential for the hatching process.The failure of embryo hatching may be one of the various factors that limited human reproductive efficiency, specifically in assisted reproductive technologies (ART) fields. Assisted hatching of human embryos before their transfer in ART program has been proposed to be beneficial, especially in cases of cultured embryos with a thick and/or dense Zona pellucida.

• A thick ZP may be associated with advanced woman's age
• An embryo with poor quality may not be able to secret the hatching factor which results in a thick zona pellucida.
• Women with an elevated baseline level of FSH.
• Women who have one or more failed IVF attempts.
• Women who are using frozen embryos which may have hardened the zona.

An artificial creation of an opening in the embryo’s zona is a useful method which might augment the implantation rates by facilitating the hatching process, and permit an earlier contact between the embryo and the receptive endometrium. The artificial opening produced by hatching may also serve as a channel for the exchange of metabolites and growth factors to and from the endometrium. In this system laser beam is delivered through the objective and thus can open zona instantaneously with a single laser plus in a few milliseconds duration.

Embryo freezing is a method of preserving the viability of embryos for extended period of time. On the day of embryo transfer, a couple may learn that they have additional embryos of good quality in addition to those embryos that have been selected for embryo transfer. These embryos can be cryopreserved by freezing them in the laboratory using specialised freezing equipment and the embryos can then be safely stored in liquid nitrogen, the method used in our lab is called vitrification. Through a series of carefully orchestrated steps, the embryos are ultimately frozen at sub zero temperature, leaving them in a state of suspended animation in which they can remain for many years. Even embryos that have been stored for more than 5-6 years have successfully generated pregnancies (although most patients tend to use their frozen embryos within 3 to 5 years after they are produced). The pregnancy rates associated with replacing frozen embryos depend on the age of the patient and the quality of the embryos at the time of cryopreservation.

Freezing embryos is appropriate for :

• Women who have made more than 3 embryos during an IVF cycle.
• Couples facing cancer treatment that may affect the eggs or sperm quality.
• Frozen Embryos can be used for next pregnancy
• It also permits the uterus environment to return to normal after the process of egg retrieval.
• Couple can also opt for genetic screening of there embryos.
• It’s a good preventive step for OHSS in cases of PCOS. We are routinely following this for our cases of Polycystic ovaries.
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• If the uterine lining is not good, it’s a good option to freeze the embryos.
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Semen freezing is the most successful method of preserving a man’s fertility so he can try and have children at a later date. The frozen sperm is just as successful as fresh sample. There are no risks from using frozen sperm in an IVF cycle.

Sperm freezing is useful in cases where :

• You have a low sperm count or the quality of your sperm is deteriorating.
• You have difficulty producing a sperm sample on the day of fertility treatment.
• Condition where multiple pooled sperm samples are taken in cases of low sperm count.
• You have a condition, or are facing medical treatment for a condition that may affect your fertility.
• You are about to have a vasectomy and want sperm available in case you change your mind about having (more) children.

The process of semen freezing firstly involves checking the male partner for viral infections like HIV, hepatitis etc. so that contamination of semen sample is avoided. Then a written, informed consent is given for sperm storage and length of time you want the sperm to be stored.

At the clinic, male partner is asked to produce a fresh sample of sperm, which will be frozen with a special fluid (a cryoprotectant) to protect the sperm from damage during freezing. The samples are then vitrified in liquid nitrogen.

Egg freezing is a method of storing your eggs to preserve fertility and allow you to have a baby later. It’s an option usually considered by women who do not want to have a baby at present, or whose fertility is at risk for medical reasons. Choosing to freeze your eggs doesn’t mean you’re depleting viable eggs from your ovarian reserve. Some women who freeze their eggs don’t use them because they later fall pregnant naturally.

During every cycle, eggs grow in fluid filled sacs (called follicles) in the ovaries. Only 1 egg will mature and be released (through ovulation), the rest will die. The egg freezing process, as with an IVF cycle, helps all the eggs to mature. The eggs stimulated to grow would have grown or died during your natural cycle that month. The stimulation mimics your body’s natural processes. It doesn’t affect future egg supply or lead to premature menopause.

Cryopreservation involves the preservation of cells and tissues for extended periods of time at sub-zero temperatures. Cryoprotective additives (CPAs) are used in order to reduce cryodamage by preventing ice formation. A recent meta-analysis of five studies found that the rates of fertilization, embryo cleavage, high quality embryos and ongoing pregnancy did not differ between vitrification and fresh oocyte groups ( Cobo and Diaz, 2011 ).

Who needs to preserve their eggs ?

• As a method for fertility preservation in cancer patients
• Women with endometriosis who may prematurely experience reduced ovarian reserve.
• Women with autoimmune diseases/Cancer treatment requiring gonadotoxic treatment
• Women with genetic aberrations leading to subfertility or risk of early menopause
• Social Egg Freezing : In todays world of Late Marriages and couples postponing to have children to when they are ready, freezing eggs at the right age is a good option which will prevent the risk of age related genetic problems later on.
• Oocyte cryopreservation can also provide an option for fertility preservation in gender reassignment surgery.
• In addition, now that assessment of ovarian reserve is widely available using biophysical (antral follicle count) and biochemical (Anti-Mullerian hormone, early follicular FSH) measures, many women who are asymptomatic are identified as being at risk of early menopause. Although ovarian reserve measurement has not been shown to have predictive value for spontaneous pregnancy, it is a reasonable strategy for these women to consider elective oocyte cryopreservation.
• Another useful application of oocyte cryopreservation arises in the situation where a male partner fails to produce a sperm sample on the day of oocyte retrieval for IVF ( Emery et al. , 2004 ). The efficacy of ‘emergency’ oocyte cryopreservation was demonstrated in cases during which sperm extraction from male partners with non-obstructive azoospermia had failed ( Song et al. , 2011 ).
• Oocyte pooling – in women who have a low antral follicle count and low AMH , eggs are retrieved over a period of 2 to 3 cycles or more and after adequate pooling, embryo transfer is done for optimal results.
• Oocyte donation - cryobanking

Fertility preservation in cancer patients Cancer treatment regimes can have a detrimental effect on female fertility, due to the removal of reproductive organs or the use of radiation therapy and cytotoxic agents. The extent of damage depends on follicular reserve, patient age, and the type and dose of treatment, with alkylating agents being particularly gonadotoxic. Advances in oocyte cryopreservation mean that it can now be offered routinely for fertility preservation. Social Egg Freezing There is an obvious gender inequality in reproduction, since men are able to reproduce at much older ages than women. Now that the cryopreservation of oocytes for age-related fertility decline is considered acceptable ,‘social egg freezing’ has become a popular subject within the media, and demand for the procedure has increased rapidly. Oocyte cryopreservation has been described as a ‘breakthrough for reproductive autonomy’ and an ‘emancipation’ for women. However, there are various reasons for which women may wish to delay motherhood, for example to focus on their career, to find a suitable partner or because they simply do not feel ‘ready’. An increasing number of women are postponing motherhood, resulting in rising numbers experiencing childlessness which they had not necessarily intended. Oocyte cryopreservation can give women the ability to make more reproductive choices; to decide when and with whom they wish to have children. The use of younger oocytes can reduce the risk of fetal loss and aneuploidies associated with ageing oocytes. The use of cryopreserved, autologous oocytes also allows the mother to have her genetically own child that could not be achieved through oocyte donation, and will provide a higher chance of pregnancy than the use of standard IVF at an older age. Age-related fertility decline The fertility decline experienced by women, which accelerates after the age of 35, is well-known. This decline is largely attributable to a decrease in follicular number and oocyte quality. If older women do conceive, they are at a significantly higher risk of fetal chromosomal abnormalities and fetal loss. Reproductive potential can be extended by the use of eggs preserved at younger age.

Blastocyst culture and transfer is a technique developed for in vitro fertilization (IVF). This procedure intends to maximize pregnancy rates while minimizing the risk of multiple pregnancies. Embryos are typically cultured for 3 days (cleavage stage with 4-10 cells) before being transferred into the uterus. By extending the culture to 5 or 6 days (blastocyst culture), some embryos will develop to the blastocyst stage (up to hundreds of cells). This allows the embryologist to select more advanced embryos with better potential for implantation at the time of the transfer.

Implantation rate is the determining factor in evaluating success in human IVF. Historically, cleavage stage transfer yields implantation rates between 10% and 30%. As a direct result of these low implantation rates, it became an accepted procedure to transfer more than one embryo to the patient to achieve acceptable ongoing pregnancy rates. The transfer of more than one embryo results in the possibility of multiple gestation. Since the implantation rate per embryo is significantly better with blastocyst transfer, one can afford to transfer only one embryo or two embryos and attain satisfactory clinical pregnancy and live birth rates, at the same time avoiding complications of multiple gestation.

It is now firmly established that the implantation potential of a blastocyst is superior to that of a cleavage stage embryo. Blastocyst grade is closely associated with the success of blastocyst transfer with good quality blastocysts giving rise to higher implantation rates compared with poor quality blastocysts.

The advantages of blastocyst transfer

• Blastocyst stage transfer is more physiological, as the endometrium is synchronized with the developmental stage of the embryo.
• Since there is activation of the embryonic genome roughly around day 3 (8 celled stage) of fertilization, a blastocyst transfer ensures that only those embryos are selected for transfer who have undergone the genomic shift. It, therefore, allows a clinician to naturally select competent embryos that have the potential of continued development under embryonic genomic control.
• It is recommended in cases where severe male infertility is involved. There are several papers showing that the male infertility significantly reduces blastulation rate. This is understandable, considering that paternal genes in the embryo are not expressed until day 3 of culture. Additionally, blastocyst culture and growth assists in the natural selection process of chromosomally competent embryos with a higher implantation potential.
• It has also been shown that most embryos with multiple aneuploidies fail to develop in extended culture unto the blastocyst stage.
• Blastocyst transfer yields a better clinical pregnancy as well as live birth rate, if one considers pregnancy rate per transfer attempt.
• Another major advantage of blastocyst transfer is its role in patients with previous multiple failed attempts at IVF.
• Blastocyst transfer could be the only option in patients with Műllerian anomalies in whom multiple pregnancies have to be avoided.
• Patients who require pre-implantation genetic diagnosis can require and benefit from a blastocyst transfer so that the results of genetic analysis are available at the time of transfer and better embryo selection can be done.

Embryo donation is a new path to parenthood that allows the opportunity for a couple that has struggled with infertility to experience the wonders of pregnancy and the joy of giving birth.

When couples undergo in-vitro fertilization (IVF) to conceive a child, often they have embryos (egg and sperm joined together) that are not used. These remaining embryos often are cryopreserved, or frozen, and put into storage for later use. Once an embryo has been cryopreserved, decisions must be made on their behalf. The embryos could be used in a future family building cycle by the family; thawed and discarded; submitted to science for research purposes; or donated to another couple that is struggling with infertility.

Many are blessed with the birth of children following IVF. If they are parenting as many children as they feel called or capable to, but still have remaining embryos, they can choose embryo donation. Through embryo donation, these individuals donate their remaining, unused embryos to a recipient, thus helping another family grow while supporting the life of the embryo

Embryo donation, sometimes called embryo adoption, offers embryos the potential of life. It also allows the recipient mother the chance to carry her adopted child and control the prenatal environment in her womb. While embryo donation is not for everyone, it can be an opportunity for many who have given up hope of giving birth to a child.

Couples who opt for embryo donation are usually who are unlikely to conceive using there own eggs and/or sperm for fertility treatment or if the couple are at risk of passing on a inherited disorder or chromosomal abnormality to the child, also couple who have experienced multiple IVF failures with there own embryos or through egg donation. A single woman opting to get pregnant or if a woman has attained menopause can also look into this option.

It’s recommended that egg donors are under 36 years of age, because fertility treatment is more successful with younger eggs. But there can be exceptions to this, such as when a woman is donating eggs to friends or family. All egg donors are screened for infectious diseases such as HIV, hepatitis B, hepatitis C, and some genetic conditions such as cystic fibrosis, before their eggs are used.

Where possible, egg donors may be matched as closely as possible with the recipient couple for characteristics such as hair colour, eye colour etc. In cases of embryo donation, the woman giving birth to the child is the legal mother. Your partner will be the other legal parent if you’re married or in a civil partnership. If not, you’ll need to sign legal parenthood consent forms before the treatment takes place.

Embryo donation / embryo adoption is a process where both eggs and sperm are sourced from Donor. Sometimes couples who undergo IVF and make extra embryos, after completing there families , can donate their extra embryos either for other infertile couples or for research purpose aswell.Otherwise couples who fail to conceive with their own gametes, can go for embryo donation/adoption cycle with both gametes from donor.

Couple with genetic disease also opt for embryo donation to prevent transmission of genetic disease to their child.

This treatment provides an answer for infertile women with ovarian problems, such as primary or premature ovarian failure. In addition, women with normal ovarian function may require oocyte donation, in cases of recurrent failure of IVF treatment.

In this process a fertile woman (donor) allows several of her oocytes to be aspirated, following ovarian stimulation, and used to enable another woman, who is infertile due to ovarian failure, to conceive with IVF.

Egg donation is useful in cases of:

• Premature ovarian failure
• Ovarian failure following chemotherapy or radiotherapy
• Previous multiple failed IVF s
• Heritable genetic diseases can be avoided with the use of donor oocytes.
• Women who have undergone bilateral oophorectomy for some reason in past.

Before donation is undertaken, oocyte donor is screened for infectious diseases. The laboratory evaluation includes a complete blood count and sedimentation rate to identify occult infection. In selected cases, haemoglobinopathies such as sickle cell trait should be ruled out. The screen for infectious diseases include serology for HIV, hepatitis B and C and syphilis. Additional specific genetic or medical testing is done if male partner of recipient has some genetic disease.

Oocyte donation involves invasive medical treatment for the donor, covering ovarian stimulation and the trans vaginal retrieval of mature oocytes under anaesthesia. Recipient can be simultaneously prepared in same cycle or embryos can be frozen and used at a later date.