IVF Failure What Next?

          IVF failure is heartbreaking and shocking to the couple undergoing fertility treatment. Since it is a costly treatment, often causes financial and psychological stress on the couple. But once a failure doesn’t mean always a failure. There are ways to get out of it. You must not lose hope and discuss further options with your IVF specialist, IVF failure what next.

What are the chances of getting pregnant with IVF?

           Even with the best of embryo and endometrium the success rate of IVF treatment is limited to 35% on an average worldwide. It may be due to the restricted natural fertility in human being. However, the following causes can be discussed for future treatment.

Why does IVF fail the first time?

          IVF failure often doesn’t have an obvious reason. Many patients conceive in the second round of IVF treatment with the same circumstances. Often patients are confused with the question IVF failure what next? First time failure may happen without any reason. Few causes of IVF failure are outlines below.

Embryo quality

       It may be due to low embryo quality. Remember to discuss with your specialist about the quality of embryo before embryo transfer. Again, this embryo quality may be due to poor eggs or sperm in the couple. Usually blastocyst culture chooses the best quality embryo and predict better success.

Egg quality

     Some women may yield poor quality eggs in IVF process. Women with PCOS, poor ovarian reserve or endometriosis are at risk of low quality eggs. Your embryologist can disclose the quality of eggs after oocyte retrieval. Further IVF process can be stopped at this point. IVF protocol also affects the quality of eggs. Hence your IVF specialist may suggest different injections and protocol after failed IVF.  Poor egg quality is caused by diminished ovarian reserve and is one of a common cause of infertility, especially in women over 35. Poor egg quality is closely associated with chromosomal abnormalities in embryos.

Endometrium

The endometrium is the layer in which the implantation (nesting) takes place. This layer experiences several changes that are closely associated with the cyclic release of female reproductive hormones. Endometrium and its receptivity is one of the causes leading to IVF failure.

    During a woman’s reproductive years, the lining of uterus, the endometrium, changes through cycles of growth, maturation and shedding. All of these changes are dependent upon a normal hormone balance by the functioning ovary. The endometrium thickens in the early phase succeeding menstruation and show a trilaminar pattern. Absence of this patter can indicate lower receptivity. Your IVF specialist may cancer embryo transfer if your endometrium doesn’t not reach 8mm in thickness or trilaminar pattern. In PCOS women often endometrium is thick and show effect of androgens. Frozen embryo transfer under down regulation can be tried for them.

The endometrium is one of the most dynamic organs in the body. Physiologically, the endometrial thickness has a wide range. It can respond to an endocrine environment by an increase in thickness in preparation for implantation or by sloughing its lining in preparation for a new cycle. Endometrial pattern and thickness are dependent on blood flow. Hence your doctor may do endometrial Doppler study for checking optimum receptive endometrium.

Hormone status

     When a woman is undergoing a fertility work-up, Cycle Day 3 is the day she has blood work performed to check the levels of three important hormones: follicle stimulating hormone (FSH), luteinising hormone (LH) and estradiol (E2). IVF failure may be attributed to any abnormalities in these tests.

The FSH blood test is used to help diagnose problems with sexual development, menstruation, and fertility. It can be used to diagnose or evaluate polycystic ovary disease, ovarian cysts, irregular vaginal bleeding and infertility.

The LH blood test measures the amount of luteinizing hormone, which is also secreted by the pituitary gland. In women, LH levels rise at mid-cycle; within 24 to 36 hours, ovulation occurs. Higher-than-normal levels of LH indicate several disorders, including ovarian failure and polycystic ovary disease.

Estradiol is the most important form of estrogen. It is primarily made in and released from the ovaries, adrenal cortex and the placenta, and it is responsible for the growth of the breasts, outer genitals, uterus, fallopian tubes and vagina.

 The natural levels of prolactin in the body change throughout the day. Levels gradually rise overnight and are at their highest in the morning. High levels of prolactin in the blood can stop the ovaries from making the hormone estrogen and may cause infertility. Thyroid hormones are important in preventing miscarriage and aiding fetal brain development. Low levels of thyroid hormone can interfere with the release of an egg from your ovary (ovulation), which impairs fertility.

Anti-Müllerian hormone (AMH), a marker of ovarian reserve, declines over a woman’s reproductive lifespan. AMH is highly correlated with a woman’s age and number of primordial ovarian follicles. AMH concentrations slowly decrease with increasing age until becoming undetectable ∼5 years before menopause.

AMH serum concentration does accurately reflect the size of the pool of antral follicles, representing the quantity of the remaining primordial follicles.

Sperm quality

   Human fertilization starts from entry of a healthy sperm into a human egg followed by mixing and division of genetic material. Fertilization usually occurs in the ampulla of the fallopian tube. The result of this union is the production of a zygote cell, or fertilized egg, initiating development of an embryo which grows into a baby.

This process requires a healthy tube, motile and healthy sperm in good numbers and a good quality egg.

Fertilization can fail due to low sperm production, abnormal sperm function or blockages that prevent the delivery of sperm. ICSI refers to the laboratory procedure which overcomes hindrance in fertilization failure due to male infertility. Through ICSI a single sperm is picked up with a fine glass needle and is injected directly into each egg. ICSI can also be done with frozen sperms. It is offered in cases of male infertility.

What causes recurrent implantation failure?

Implantation is referred to the stage of pregnancy at which the embryo adheres to the wall of the uterus. It helps the embryo to grow by receiving nutrients from the mother.

In humans, implantation of a fertilized ovum is most likely to occur around 6 – 9 days after ovulation. The reception-ready phase of the endometrium of the uterus is usually termed the “implantation window” and lasts about 4 days.

The initial phase of the implantation process is attachment of embryo to maternal tissue. This first phase requires the newly hatched blastocyst to loosely adhere to the endometrial epithelium, often “rolling” to the eventual site of implantation where it is firmly adhered. This process requires both the blastocyst adhesion interaction with the endometrium during the “receptive window”.

The term “implantation” is used to describe process of attachment and invasion of the uterus endometrium by the blastocyst (conceptus).

Implantation is a highly-coordinated event that involves both embryonic and maternal active participation.

Initially the newly hatched blastocyst loosely adheres to the endometrial epithelium. Then it rolls over the endometrium to find a suitable place for implantation where it gets attached firmly.

        Various structural problems in endometrium can lead to failure. Polyps (small growth), presence of septum (partition dividing endometrial cavity), fibroid uterus also can lead to recurrent Implantation failure.

What happens when IVF doesn’t work?

    Extreme stress may affect fertility, women with high levels of alpha-amylase, an enzyme that correlates with stress, have difficulty in getting pregnant.  Stress can affect the functioning of the hypothalamus and the hormones that controls ovaries to release eggs. Physical stress or emotional stress does interfere with menstrual cycle and alters the release of eggs. Stress and depression can lead to miscarriages.

The risk of depression, anxiety, and distress is high for infertile patients.  However, the impact of distress on treatment outcome is less definitive. More depressed infertile woman, are less likely to start infertility treatment and the more likely to drop out after only one cycle. Psychological interventions for women with infertility have the potential to decrease anxiety and depression. This may well lead to significantly higher pregnancy rates.

How to improve quality of eggs?

Women doing IVF with their own eggs experience a significant decrease in success rates as age advances. The difference in egg quality between a 25-year-old and a 40-year-old is significant. This may be due to the progressive DNA damage of the eggs. Healthy lifestyle and diet can prevent this damage and yield better quality eggs.

Poor egg quality is caused by diminished ovarian reserve and is one of a common cause of infertility, especially in women over 35. Poor egg quality is closely associated with chromosomal abnormalities in embryos.

What are the options after failed IVF?

IVF failure is not the end of story, you can discuss the further course of treatment with your fertility specialist. Femelife Fertility offers a great range of treatment after IVF failure in first time. Our Medical Director, Dr. Nabaneeta Padhy goes through the details of each couple’s profile for possible causes of failure. You can have a variety of reasons or no reasons at all. But following options can be discussed with your IVF specialist.

Blastocyst culture

      Blastocyst is an embryo which has developed to day 5 stage with different cell components and a fluid cavity.

The advantage of blastocyst cultures is the selection of best embryo because only the embryos with high potential for development reach the blastocyst stage.  Pregnancy chances are high when using a blastocyst then with an embryo of day 2 or 3 development. Frozen embryo transfer is more successful with blastocysts as they survive the freezing and thawing process well. Blastocysts are also used for embryo diagnosis in PGD. Blastocyst cultures are particularly useful when a good yield of eggs is obtained. With lower number of eggs there is risk of failure of development into blastocyst.

Assisted hatching  

Assisted hatching is a laboratory procedure that is sometimes done along with in vitro fertilization (IVF) treatment. During assisted hatching, the outer shell of the embryo is artificially weakened by making a small hole in the outer covering called zona pellucida. Assisted hatching may help the embryo to implant into the uterine wall, and   lead to a pregnancy.

Experts do not recommend the use of assisted hatching in all patients undergoing IVF treatments. Rarely, assisted hatching can damage the embryo, making it unusable. The risk for identical twins might be slightly increased when assisted hatching is applied. Medical complications are higher in identical twin pregnancies than in normal, singleton pregnancies.

Frozen embryo transfer 

 Embryo cryopreservation is useful for surplus embryos during in vitro fertilization. Patients who fail to conceive may become pregnant using frozen embryos in subsequent cycles. Successful patients in IVF treatment may come back later for frozen embryo transfer to achieve a sibling pregnancy. Cryopreservation was applied to humans beginning in 1954 with three pregnancies resulting from the insemination of previously frozen sperm. Clinical pregnancy and live birth rates of fresh and frozen ETs are not significantly different.

Donor egg programme

Egg donor IVF is a fertility treatment option for those who can’t use their own eggs due to various reasons. The egg donation process involves retrieving eggs from a woman who has normally functioning ovaries. Following egg retrieval, the eggs are fertilized in the in vitro fertilization (IVF) lab using sperm from the receiving couple’s partner, or in certain situations with donor sperm.

Female infertility is defined as a failure to achieve a successful pregnancy after 12 months. The quality of oocytes plays an important role in determining fertility outcomes. It is well known that increasing maternal age has a negative impact on the ability of an oocyte. Donor eggs and embryos can bypass the problem, but not everyone accepts third-party genetic involvement.

Donor sperm IVF

     At present among all infertility cases, approximately 40–50% is due to “male factor” infertility. Many men as exhibit suboptimal sperm parameters due to increasing pollution and lifestyle diseases. In these conditions fertility has dropped down and cases of male infertility are increasing. If there is decrease in sperm count or number of healthy sperms then the couple face difficulty in achieving a healthy pregnancy and IVF failure chances are high. If your male partner is having low count you doctor may advise for ICSI treatment. But in some cases, ICSI may not be possible due to poor quality of sperm. In such cases chances of fertilization failure is high and pregnancy if happens may end in miscarriages. To avoid such a situation your doctor may offer you use of an anonymous donor matching to the profile of your male partner.

Embryo donation

        For some couple embryo donation may the last resort. The IVF specialist offers embryo donation if both egg and sperm quality is not good and pregnancy doesn’t happen instead of trying multiple times. Good quality embryos in eight cell stage or blastocyst can help to achieve pregnancy in such cases. Repeated implantation failure or recurrent miscarriage can be treated in this way.

Surrogacy

       People require surrogacy treatment when pregnancy is medically impossible or risky for the would be mother. Surrogacy is a legal agreement, whereby another woman not related to the child genetically carries the pregnancy and delivers for the biological parents. Receiving money for the arrangement is known as commercial surrogacy, which is right now under radar in India. In some countries, surrogacy is only legal if money does not exchange hands.  Surrogacy may be traditional or gestational, depending on the genetic origin of the egg.

Mitochondrial transfer

           Mitochondrial transfer is a new technology developed to help couple having genetic abnormality. Mitochondrial transfer also called three parent baby has recently emerged to prevent the transmission of a certain class of genetic disorders. Mitochondrial of the cell also contains DNA which if abnormal causes health issues in the child. A baby gets the nuclear DNA, in equal parts from both parents, but mitochondria DNA is inherited solely from the mother. So, when a mother has damaged mitochondrial DNA, she passes this on to all of her children causing disease. To prevent such transmission while still retaining her genetic material mitochondrial transfer helps. In this process, the egg of mother is taken but the mitochondria are replaced healthy mitochondria from another woman’s donated egg. This first child born in this process was in Mexico in 2016.

PGD/PGS

 PGD is a genetic test on cells removed from embryos, to help select the best embryo. PGD may be advised to couples at increased risk for chromosome abnormalities or specific genetic disorders or women who have had several miscarriages. This is also done in women who have had a prior pregnancy with a chromosome abnormality or women over 38 years of age and men with some types of sperm abnormalities. Most IVF failures can be accounted for by embryonic aneuploidy. Recurrent IVF failure (RIF) is usually defined as 3 or more failed IVF attempts involving high-quality embryos

Low sperm count, poor morphology, and poor motility in men with severe infertility has been linked to the generation of embryos with an increased incidence of inherited chromosomal abnormalities. Genetic defects found to be associated with male factor infertility includes aneuploidy, most commonly Klinefelter syndrome, Robertsonian translocations, Y chromosome microdeletions, androgen receptor mutations, and other autosomal gene mutations.

The use of PGS/PGD in couples with severe male factor infertility may decrease pregnancy rates but also limits the prevalence of chromosome abnormalities.

   Mitochondrial transfer and other assisted reproductive technologies have aroused biological, ethical, and legal concerns. But for infertile couples looking a solution they throw a ray of hope. In a world where designer babies could be just around the corner IVF failure can be overcome.Science is developing rapidly so is reproductive technology. Human reproduction is better understood in this era and is being applied to treat infertility. IVF failure what next question is being answered at all stages. Don’t worry if IVF fails, there are alternative methods.

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