How common is male factor infertility and what proportion of infertility in the couple is attributable to the male?
Of all infertility cases, approximately 40–50% is due to “male factor” infertility and as many as 2% of all men will exhibit suboptimal sperm parameters.
The rates of infertility in less industrialised nations are markedly higher and infectious diseases are responsible for a greater proportion of infertility.
The fertility rate in men younger than age 30 years has also decreased worldwide by 15%.
Is it necessary for all infertile men to undergo a thorough evaluation?
If you are facing difficulty in conceiving then semen analysis should be done at the earliest.
Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.
Males with sperm parameters below the WHO normal values are considered to have male factor infertility.
The most significant of these are low sperm concentration (oligospermia), poor sperm motility (asthenospermia), and abnormal sperm morphology (teratospermia).
Semen analysis remains the single most useful and fundamental investigation with a sensitivity of 89.6%, that it is able to detect 9 out of 10 men with a genuine problem of male infertility.
What is the clinical value of traditional semen parameters?
Males with sperm parameters below the WHO normal values are considered to have male factor infertility.
The most significant of these are low sperm concentration (oligospermia), poor sperm motility (asthenospermia), and abnormal sperm morphology (teratospermia).
What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)?
Cigarette smoke is a common somatic cell carcinogen and mutagen, and may adversely affect male reproduction factors.
Obesity is also linked to subfertility due to alteration in the hormone environment. Constant exposure to lead for instance, without safety measures, predisposes such individuals to low fertility.
Men who are exposed to high temperature at their workplace – welders, dyers, blast furnace workers and those employed in cement and steel factories – are more prone to infertility. A 1° elevation in testicular temperature leads to 14% depression of spermatogenesis.
Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men?
Oxidative stress in the seminal fluid causes damage of the sperm plasma membrane and loss of its DNA integrity. Normally, a balance exists between concentrations of reactive oxygen species and antioxidant scavenging systems. If oxidative damage exceeds natural scavenging capacity then it affects sperm parameters. High dosage of vitamin C & E may rescue from such damage and increase fertility in male factor infertility.
What are the evidence-based criteria for genetic screening of infertile men?
Genetic testing is required in all severely oligospermic and non-obstructive azoospermic men. Such men demonstrate small testes and increased FSH. Chromosome structural and numeric abnormalities, YCMD, and other genetic mutations have been implicated in male subfertility. These men may benefit from genetic testing.
How does a history of neoplasia and related treatments in the male impact on reproductive health and fertility options?
Cancer, or post cancer treatments, can interfere with male factor fertility and reduce the ability to have children. Different types of treatments can have different effects.
Higher doses of cancer drugs are more likely to cause permanent fertility changes. The combinations of drugs can have greater effects. The risks of permanent infertility are even higher when males are treated with both chemo and radiation therapy.
What is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?
Varicocele is among the most common causes of male infertility. Varicocele affects fertility and sperm quality in some, but not in all men. The adverse effect of varicocele on sperm parameters may be due to increased testicular temperature, increased pressure, or reduced blood flow.
Effectiveness of varicocelectomy is however not proved and hence not practiced in many infertility setup.
Success in IVF Treatment
Lesley Brown was a patient with nine years of primary infertility who sought the assistance of Patrick Steptoe and Robert Edwards at the Oldham General Hospital in England in 1970’s. At that time, she was unaware of the historical revolution in IVF treatment she was going to be associated with. Fertilisation of oocytes outside the human body, a process known as in vitro fertilisation (IVF), was considered entirely experimental and unsuccessful around that period. Without using medications to stimulate her ovaries, Lesley Brown underwent laparoscopic egg retrieval, with her single egg fertilised in the laboratory, and later transferred back into the uterus. The embryo transfer resulted in the first live birth from IVF, a daughter Louise Brown, who was born in July 1978.
Introduction of ovarian stimulation and Success with traditional IVF
The success of IVF treatment with unstimulated cycles yielded on average 0.7 oocytes per retrieval and an overall pregnancy rate of 6% per initiated cycle at that time. Stimulated IVF cycles with human menopausal gonadotropin (hMG) prior to laparoscopic egg retrieval was extensively studied at the Jones Institute after 5 years. Its widespread use led to dramatic improvement in oocyte yield per retrieval and pregnancy rates. Between 1980 and 1983, the use of hMG with IVF treatment resulted in an average recovery of 2.1–2.6 oocytes per retrieval and increasing pregnancy rates of 23.5% per retrieval in 1982 and 30% in 1983.
Pituitary desensitisation by administration of gonadotropin releasing hormone agonist (long protocol) prior to ovarian stimulation with hMG was first reported in 1984. Effective suppression with this protocol decreased the incidence of premature ovulation to about 2% and significantly improved overall pregnancy rates with IVF.
Pregnancy rates in women using donor oocytes are known to be as high as 50% per embryo transfer in recipients across all age groups. Indeed, women in their sixties have also given birth with donor oocytes, demonstrating that the postmenopausal uterus maintains the capacity to support pregnancies if provided adequate hormonal support. Despite these unresolved issues, donor IVF remains an integral part of modern ART, and accounts for 11.6% of the IVF treatment cycles.
Development of different types of protocol
Freezing techniques in IVF
Intense efforts to develop various freezing/thawing techniques and cryoprotective agents eventually resulted in the first reported human pregnancy from a frozen embryo in 1983, which unfortunately ended in premature rupture of the membranes and termination of pregnancy at 24 weeks of gestation. Despite the initial set back, technology in cryopreservation continued to improve throughout the 1980s, leading to an increase in embryo survival rate and pregnancy rates. During the initial years of experimentation, at best approximately 50% of embryos survived the freeze/thaw process and resulted in a pregnancy rate of 13.4% per embryo transfer procedure, as only 4.6% of the individual thawed embryos implanted
ICSI revolutionised Artificial Reproductive Techniques
As the pregnancy rate of IVF improved over the last decade from 22.3% in 1995 to 33% in 2003. In 2003, GIFT and ZIFT were used in only 0.1% and 0.4% of ART cycles, while IVF represented the remaining 99.5% of cases.
The first pregnancies using embryos generated by ICSI were reported in 1992 (Palermo et al 1992) and the procedure has been applied increasingly from 11% of IVF treatment cycles in 1995 to 55.6% in 2003. Fertilisation rates as high as 70% can be achieved with testicular sperm extraction (TESE) despite only using a few poor-quality sperm. The first clinical application of the procedure called preimplantation genetic diagnosis (PGD) was used in 1990 to prevent the transmission of two X-linked conditions: adrenoleukodystrophy and X-linked mental retardation
Better Freezing success with Vitrification
Currently, each thawed oocyte has a mean survival rate of 47%, fertilisation rate of 52%, but pregnancy rate of only 1.52% . Other methods to circumvent oocyte damage caused by the freeze/thaw process include vitrification and cryopreservation of germinal vesicles. Vitrification uses high concentration of cryoprotectants to solidify the cell into a glass-like state without the formation of ice. Based on a small study, post-thaw survival rates and pregnancy rate of this approach were 68.8% and 21.4%,
Ovarian tissue cryopreservation, achieved by biopsy and cryopreservation of ovarian cortex containing primordial follicles, followed by thawing and transplanting the autograft after completion of cancer treatment offers a potential solution in those circumstances. Transplantation can be either orthotopic (in close proximity to the infundibulo-pelvic ligament) or heterotopic (ie, forearm or abdomen). improving the efficiency of oocyte cryopreservation and of ovarian tissue transplantation promises to provide options to women who must delay childbearing.
Thyroid hormone is produced by the thyroid gland present at the neck and is controlled by Thyroid Stimulating Hormone (TSH) to produce more hormones when needed. Elevated TSH levels can be a sign that the thyroid gland is under-active. When thyroid function is not sufficient to meet, your body’s needs it is called hypothyroidism.
Hypothyroidism can lead to infertility, increased miscarriage risk, and complications in both mother and baby. 50 to 70% of hypothyroid female patients have menstrual abnormalities. Many present with oligo menorrhea (scanty bleeding during cycle). Severe hypothyroidism is commonly associated with failure of ovulation and infertility. Ovulation and conception can occur in mild hypothyroidism. But these pregnancies are at risk of abortions, stillbirths, or prematurity.
If you are trying to conceive then proper evaluation of thyroid hormone function is essential. In fact, thyroid tests are included in basic hormone tests for infertility.
What is subclinical hypothyroidism?
SCH is classically defined as a thyrotropin (TSH) level above the upper limit of normal range (4.5−5.0 mIU/L) with normal free thyroxine
(FT4) levels. Women with unexplained infertility more commonly present with this condition than women with infertility due to a known cause.
Should non-pregnant women be treated for SCH (subclinical Hypothyroidism)?
There is no benefit from the standpoint of lipid profile or alteration of cardiovascular risk in non-pregnant women. The risk of over-treatment with thyroid hormone can result in bone loss. Hence refrain from self-treatment with thyroid hormone and consult your doctor for proper advice.
How does your thyroid affect your pregnancy?
TSH levels outside the normal pregnancy range are associated with an increased risk of pregnancy complications as placental abruption, preterm birth, foetal death, and preterm breaking of waters (premature rupture of membranes). If you are taking thyroid medications then you should continue the treatment during pregnancy. Regular tests will guide you to dosage adjustments in pregnancy.
Can you get pregnant if you have thyroid problems?
Unexplained infertility and ovulatory disorders can cause infertility in patients with low thyroid hormone levels. But you can still conceive with thyroid problem. In this scenario, you must consult you treating doctor for prevention of complications in pregnancy.
Can a thyroid problem cause a miscarriage?
Low thyroid hormone is associated with adverse reproductive outcomes. The problems include miscarriage, pregnancy complications, and delayed foetal neurodevelopment. There is fair evidence that thyroid autoimmunity (positive thyroid antibody) is associated with miscarriage and infertility. Treating TSH levels >4.0 mIU/L is associated with improved pregnancy and miscarriage rates.
What should be the thyroid level during pregnancy?
The Endocrine Society recommends the following pregnancy trimester guidelines for TSH levels: 2.5 mIU/L is the recommended upper limit of normal in the first trimester,
3.0 mIU/L in the second trimester, and 3.5 mIU/L in the third trimester.
Should there be universal screening for hypothyroidism in the first trimester of pregnancy?
The American College of Obstetricians and Gynaecologists does not recommend routine screening for hypothyroidism in pregnancy unless women
have risk factors for thyroid disease. During your pregnancy, a thyroid test may not be advised if you don’t have any symptoms or risk factors. But women
at high risk for thyroid disease should be screened.
Does thyroid affect pregnancy baby?
Untreated maternal hypothyroidism can cause delayed foetal neurologic development. Children delivered to mother with untreated hypothyroid may show impaired school performance, and lower intelligence quotient (IQ).
Can thyroid cause birth defects?
Delayed foetal neurodevelopment can result from thyroid deficiency in pregnancy. Thyroid maternal under function, even when considered mild (or subclinical), may be associated with an impairment of brain development of the baby.
If you are taking thyroid hormone you will need regular checks to adjust dosage. You should not discontinue treatment without proper advice form physician. During pregnancy, you may have to alter the dosage. Regular pregnancy checks are required to prevent any complications in mother and baby.
Surgeries that can enhance fertility
Fertility enhancing surgeries are usually advised to young women with suspected minimal to moderate disease of tubes, ovaries or uterus. These surgeries may enhance the rate of spontaneous pregnancy or IUI treatment. Usually such surgeries are done by experts through laparoscope to prevent damage to pelvic organs.
Fertility enhancing surgeries in female infertility
Uterine fibroids are the most common tumours in the female. Fibroids in infertile women undergoing assisted reproductive treatment can decrease success rates than do age-matched women with no fibroid. Removal of fibroids(myomectomy) can help these cases. However, myomectomy is restricted to women with unexplained infertility. If you have fibroids growing into the uterine cavity then you are more likely to benefit after myomectomy. Higher pregnancy rates can be achieved after laparoscopic removal than open surgery. This procedure can be considered if you are suffering from infertility for long years.
Tubal sterilization is one of the most commonly used contraceptive methods worldwide. Approximately 1% of the women who undergo this procedure may request reversal of the procedure to restore fertility. However, if you are going for this procedure you must be aware of its cost benefit analysis. Due to its low success rate, often IVF is preferred to tubal anastomosis. Tubal anastomosis by the laparoscopic approach has the advantages over open surgery. Less postoperative discomfort and fewer complications, a smaller incisional scar, a shorter recovery time, and earlier resumption of normal activities are the advantages of laparoscopic procedure. This could be especially beneficial for a patient who previously has undergone a laparotomy or caesarean section because it allows her to avoid a second surgery.
Patient selection as well as meticulous surgical technique are key factors in achieving satisfactory pregnancy rates.
Excision of endometriosis:
In women with minimal and mild endometriosis, surgical removal or thermal destruction(ablation) of endometriosis is recommended as first line with higher success rate.
Laparoscopic surgery for destruction of mild endometriosis almost doubles the spontaneous pregnancy rate. IVF is the best option for patients after failed primary surgery. Repeat surgery is associated with lower pregnancy rate.
The pregnancy rate after intrauterine insemination IUI may be increased after surgery for mild endometriosis. The place of IUI is limited in patients with moderate or severe endometriosis and in older women. The incidence of recurrence of endometriosis is not increased after ovarian stimulation for IVF.
Ovarian cysts commonly are simple cysts(functional)or chocolate cysts (endometrioma).
Functional cysts, unless they become very large, these types of ovarian cysts don’t affect fertility. Hence your doctor may prefer to wait and watch for growth of these cysts. Small cysts may regress on their own.
Ovarian endometriomas are managed by laparoscopic procedures, like cyst aspiration or excision.
Distal tubal disease and tubal reconstruction:
These procedures are of minimal benefit for fertility. At times these surgeries can be done for young patients with hydro salpinx who don’t want to go for IVF. Of all surgical treatments for tubal disease, sterilization reversal results in the highest pregnancy rates. The procedure is appealing to couples who desire an extended family or who are not comfortable with IVF. The ectopic pregnancy risk and the need for future contraception are recognized disadvantages with these procedures.
Benefits of bariatric surgery for obesity:
Obese men and women may benefit from weight loss programme or surgical removal of fat content from body.
Polycystic ovary syndrome (PCOS) is the most frequent cause of female infertility. It is often associated with obesity. PCOS, hirsutism, and menstrual irregularities improve after bariatric surgery. The increased risk of miscarriage in obese women may decline after bariatric surgery.
Obesity can be associated with reduced sperm concentrations. Weight loss is the cornerstone of the treatment of obesity-related infertility. It can restore fertility and normal hormonal profiles. But effects of bariatric surgery impact on male fertility is still unclear. At times sperm counts may be adversely affected by fat loss surgery.
Laparoscopic adhesiolysis still remains a useful and effective procedure for infertile couples with pelvic adhesions. These adhesions may be a result of previous surgery or infections like abdominal tuberculosis.
Although septate uterus does not seem to be an infertility factor hysteroscopic septum resection is accompanied by a significant improvement in the reproductive performance. There is no adverse effect in the achievement of pregnancy in women with a history of recurrent abortions after septum removal.
Hysteroscopic septum resection in women with septate uterus significantly improves the live birth rates and future fertility is also not impaired.
Metroplasty refers to repairing the womb with birth defects like extra horn, double uterus or divided uterus. Women with uterine partition(septum) and otherwise unexplained infertility might benefit from hysteroscopic metroplasty.
Ovarian drilling is done in women with PCOS to break the thick outer surface and destroy some of the testosterone producing tissue made by the ovaries. This can help the ovaries release an egg each month and start regular monthly menstrual cycles. This may reduce symptoms of excess testosterone as well.
The uterine transplant is the surgical procedure whereby a healthy uterus is transplanted into an individual who does have one from birth or got it removed for disease process. Although it appears as a breakthrough procedure in the field of infertility its results are yet to be studied.
Surgery for Ectopic pregnancy:
Surgery for ectopic pregnancy usually involves the fallopian tubes. It is aimed at preserving the tubes for future fertility but recurrence of ectopic is common in such situations.
Fertility enhancing surgery in male infertility
Varicocele is one among the most common causes of male infertility. The adverse effect of varicocele on spermatogenesis can be attributed to an increased testicular temperature. The results of varicocele surgery are not conclusive and not encouraging for restoring fertility. Hence this is reserved for people with severe grade of the disease. ICSI is an alternative method of fertility treatment in these patients.
TESA, PESA, MESA & Testicularbiopsy:
These are procedures of sperm retrieval for patients undergoing ICSI treatment. Usually these procedures are advised in patients with azoospermia with blockage of the passage (vas deferens).
Reversal of vasectomy:
Vasectomy reversal is surgery to undo a vasectomy. Success rates with vasectomy reversal will range from about 40 percent to over 90 percent. In some cases, pregnancy, still may not happen after a vasectomy reversal, even when there is sperm. This may be due to decreased motility of sperm.
Fertility Enhancing Surgeries
Why HSG (Hysterosalpingogram) is done?
Hysterosalpingogram ( HSG) is a type of X-Ray of abdomen to know the condition of the fallopian tubes. If the fallopian tubes are blocked then couple may have difficult in conceiving, it is required to check whether tubes are open or not in cases of infertility. It’s also used to investigate miscarriages resulting from abnormalities within the uterus such as tumour masses, adhesions and uterine fibroids.
What is HSG
What is a Hysterosalpingogram (HSG)?
HSG is a diagnostic X-Ray procedure that usually takes around 15 minutes to perform. It is usually done before ovulation around 10 -12 days after menstruation. This is done on an outpatient basis.
How the patient is prepared for HSG?
The doctor usually obtains history regarding pregnancy and any allergies as HSG should not be done on a pregnant woman. Any kind of allergies should be noted as the dye used in this procedure may cause severe reactions in such people. This procedure should not be performed in inflammatory condition like chronic pelvic infection or an untreated sexually transmitted disease. Since the dye used may damage a developing foetus doctors advise to take contraceptive pills in the cycle when HSG is done in order to prevent pregnancy. The patient is also given antibiotics to prevent infection and also at times a pain killer to reduce the discomfort during the procedure.
How is a Hysterosalpingogram done?
Hysterosalpingography uses a real-time form of x-ray called fluoroscopy to examine the uterus and fallopian tubes
A woman is positioned under a fluoroscope (an x-ray imager that can take pictures during the study) on a table. The doctor then examines the patient’s uterus and places a speculum in her vagina. Her cervix is cleaned, and a cannula is placed into the opening of the cervix. A liquid containing iodine (a fluid that can be seen by x-ray) is slowly pushed through the cannula. The contrast is seen as white on the image and can show the contour of the uterus as the liquid travels from the cannula, into the uterus, and through the fallopian tubes. If the tubes are blocked the dye doesn’t pass through and may cause swelling of the tubes called hydrosalpinx.
After the HSG, a woman can immediately return to normal activities but refrain from intercourse for a few days.
Does HSG cause pain?
An HSG usually causes mild or moderate cramping pain for about an hour. However, some women may experience cramps for several hours. These symptoms can be greatly reduced by taking medications used for menstrual cramps like pain killers before the procedure or when they occur.
What are the risks of HSG?
HSG is considered a relatively safe procedure. However, some complications mild or serious can happen in less than 1% of the time. There is always a slight chance of cancer from excessive exposure to radiation. However, the benefit of an accurate diagnosis far outweighs the risk. The effective radiation dose for this procedure varies. Special care is taken during x-ray examinations to use the lowest radiation dose possible while producing the best images for evaluation.
In the event of a chronic inflammatory condition, pelvic infection or untreated sexually transmitted disease, be certain to notify the physician or technologist before the procedure to avoid worsening of infection.
Women should always inform their physician or x-ray technologist if there is any possibility that they are pregnant.
- The most common serious problem with HSG is pelvic infection. This usually occurs when a woman has had previous tubal disease (such as a past infection of chlamydia). In rare cases, infection can damage the fallopian tubes or make it necessary to remove them. A woman should call her doctor if she experiences increasing pain or a fever within 1-2 days of the HSG.
- Fainting – Rarely, some woman may get light-headed during or shortly after the procedure and faint due to a vasovagal attack.
- Iodine Allergy – Rarely, a woman may have an allergy to the iodine contrast used in HSG. A woman should inform her doctor if she is allergic to iodine, intravenous contrast dyes, or seafood. Women who are allergic to iodine should have the HSG procedure performed without an iodine-containing contrast solution. If a woman experiences a rash, itching, or swelling after the procedure, she should contact her doctor.
- Spotting – Spotting sometimes occurs for 1-2 days after HSG. Unless instructed otherwise, a woman should notify her doctor if she experiences heavy bleeding after HSG.
What are the limitations of HSG?
Hysterosalpingography only sees the inside of the uterus and fallopian tubes. Abnormalities of the ovaries, wall of the uterus, and other pelvic structures may be evaluated with MRI or ultrasound. Alternatively, a surgical procedure to directly view the tubes (laparoscopy) can be done which is more accurate than HSG.
What is the next step if tubes are found to be blocked on HSG?
Patients may undergo revaluation of tubes with laparoscopy or may be suggested to go for IVF. In vitro fertilization (IVF) is a procedure which can bypass the function of the tubes and can achieve pregnancy in cases with the blocked fallopian tubes.
What is HSG
The Process of Implantation and IVF Success
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 fertilised 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 term “implantation” is used to describe process of attachment and invasion of the uterus endometrium by the blastocyst (conceptus).
Implantation is a highly co-ordinated 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.
What happens in implantation window?
Embryo–endometrial dialogue has led to the identification of a ‘window of implantation’. The implantation window is characterised by changes to the endometrium cells, which aid in the absorption of the uterine fluid. These changes bring the blastocyst nearer to the endometrium and immobilise it. The first step of implantation is the formation of foetal–maternal interface. Next crucial step is invasion of the embryo into the endometrium.
How implantation is mediated?
Implantation is initiated when the blastocyst comes into contact with the uterine wall. Certain molecules and pinopodes are involved in bringing embryo and endometrium together and attachment in embryo implantation. The embryo produces cytokines and growth factors and receptors for endometrial signals.
Does body immunity play role in successful pregnancy?
The embryo, as a genetic product of both maternal and paternal chromosomal material, can be seen as an allograft to the uterus. The body immune system plays an important role in implantation process. The host (mother)genetically different from the transplants(foetus), raises the possibility of a graft-versus-host reaction. The immunological action against the embryo can be described as maternal restraint.
Can we calculate Implantation period?
Implantation of a fertilized ovum is most likely to occur around 6 – 9 days after ovulation. It falls around day 21 of a regular menstruation cycle. In irregular cycles, it is difficult to predict. During the female fertile age, there is an average chance of pregnancy of approximately 15% per cycle.
Does implantation process differ in IVF and natural pregnancy?
The assisted reproduction setting for implantation is not different to a naturally conceived pregnancy.
But at times, during IVF treatment, the factors for implantation may be adversely affected. This is attributed to high level of steroid hormones and drugs used for pituitary desensitization. Imbalance in the oestrogen and progesterone interaction may result in implantation failure in a number of patients.
Can we enhance implantation by PGD?
Embryonic factors are by far the main factors determining whether or not a successful implantation and pregnancy will occur.
PGD seems to be a safe procedure that can enhance pregnancy rates by improving embryo quality by selection. Preimplantation genetic screening (PGS) enables the testing of gametes and embryos for numerical chromosomal aberrations commonly found in early pregnancy loss.
What are the early signs of implantation?
Embryonic implantation is the establishment of pregnancy, to be proven by finding human chorionic gonadotrophin (HCG) in maternal blood. Some women may experience slight bleeding and cramping pain during the process of implantation.
What is the role of embryo transfer procedure in implantation?
The performance of an atraumatic embryo transfer is essential to implantation and IVF success. Factors such as the contamination of the catheter tip with cervical bacteria, stimulation of uterine contractions during the procedure, may significantly influence implantation rates. Usually embryo transfer is performed under ultrasound guidance by use of soft catheters for better success.
What is recurrent implantation failure?
Recurrent implantation failure is an important cause of repeated IVF failure. It is estimated that approximately 10% of women seeking IVF treatment will experience this particular problem. It is a distressing condition for patients and frustrating for clinicians and scientists. Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years. The failure to implant may be a consequence of embryo or uterine factors.