Infertility

Couples may consider seeking medical advice if: 

• They have been trying unsuccessfully within the timeframes above 
• The female partner has irregular or absent menstrual cycles 
• There are known medical or reproductive issues in either partner 

You may start with an obstetrician-gynaecologist (OB/GYN) or consult a reproductive specialist directly. 

• OB/GYNs can perform initial tests and treatment 
• Reproductive specialists provide more advanced fertility care 

As fertility declines with age, particularly after the age of 35, early assessment improves treatment options and outcomes. 

Female Factors 

• Ovulation disorders (e.g. polycystic ovary syndrome) 
• Fallopian tube blockage or damage 
• Endometriosis 
• Uterine conditions (e.g. fibroids, polyps) 
• Age-related decline in egg quality and quantity 

Male Factors 

Male factors contribute to 30–50% of infertility cases and include: 

• Low sperm count 
• Poor sperm motility (movement) 
• Abnormal sperm shape 
• Hormonal or genetic conditions 
  

Lifestyle Factors That Affect Fertility 

Fertility in both men and women can be affected by lifestyle factors such as: 

• Smoking 
• Excess alcohol consumption 
• Obesity or being underweight 
• Chronic stress 
• Poor sleep and nutrition 

Adopting a healthy lifestyle may improve fertility outcomes. 

Unexplained Infertility 

In some couples, no clear cause is identified despite evaluation. 

For women with irregular or absent ovulation, medications such as Clomiphene citrate and Letrozole may be prescribed. These help stimulate hormone signals that encourage the ovaries to develop and release an egg. 

• Around 70–80% of women will ovulate with these medications 
• Taken for 5 days early in the menstrual cycle 

These drugs are typically well tolerated but some possible side effects can occur: 

• Hot flushes 
• Breast tenderness 
• Mild pelvic discomfort 

There is a 5–8% chance of twin pregnancy.  

In some women, Clomiphene citrate can cause thinning of the endometrium (womb lining where pregnancy implants). If this occurs, Letrozole may be prescribed instead.  

In the unlikely event that these oral drugs fail to result in ovulation, gonadotropin hormonal injections can be considered. 

This procedure is performed using a transvaginal ultrasound scan to assess the response of a woman treated with ovulation induction drugs.  

• Monitoring usually begins on day 12 of the menstrual cycle to check if a dominant follicle is developing.  
• This process is repeated every 2 to 3 days until the follicle reaches a diameter of about 18mm or, if no dominant follicle emerges, monitoring is discontinued.  
• When the follicle reaches a diameter of 18mm, this is the fertile period and the couple is advised to have sexual intercourse.  

If no dominant follicle emerges, adjustment of the drug dose, type of drug or change in the form of treatment (i.e. fertility injections) will be advised for the subsequent cycles.

Couples who demonstrate moderately poor quality sperm, sexual dysfunction or unexplained infertility may be suitable for IUI.  

What does the IUI process involve?  

• Serial ultrasound scans for the woman to monitor the growth of the follicle (which contains the egg). Once the size of the ovarian follicle reaches approximately 18mm, she will be given a subcutaneous injection, hCG, to mature the egg within the follicle and induce ovulation.  
• Intrauterine insemination is performed 36 to 40 hours after the hCG injection. 
• The man will be required to produce his semen sample on the morning of the IUI procedure. The sample will then be prepared in the laboratory so that the best quality sperm are selected.  
• The procedure itself is quick and painless. A speculum will be placed in the vagina to visualise the cervix. The sperm preparation is then placed in the uterus using a thin catheter.  

If the man is unable to be physically present during the IUI, it is possible for him to provide the semen sample in advance and for the specimen to be frozen. On the day of the IUI, the sample will be thawed and prepared in the usual way. However, it is advisable to provide a fresh semen sample as sperm quality is more easily assessed with fresh sperm.  

What are the risks of IUI?  

Natural cycle IUI (without ovulation induction drugs) does not pose much risk at all. Stimulated IUI can lead to multiple follicular growth, increasing the chance of a multiple pregnancy and a small risk of ovarian hyperstimulation syndrome.  

What is the success rate of IUI? 

The success rate is approximately 10% per cycle, which varies depending on age, the cause of infertility, and whether ovarian induction drugs are used.  

How many times can a couple attempt IUI? 

IUI can be attempted as many times as the couple wishes. However, the likelihood of success decreases with increasing numbers of failed IUI.  

The couple must also remember that fertility declines with age. The current recommendation is to proceed with in-vitro fertilisation (IVF) after 3 failed attempts of IUI.

IVF is a technology that introduces the female egg (oocyte) and male sperm together in a specialised culture medium where the chances of successful fertilisation are greatly enhanced.  

The embryos are observed and grown in our IVF laboratory, where they are graded for quality and reintroduced to the woman’s uterus at the multicell embryo stage or later at the blastocyst embryo stage. 

A thorough evaluation of both partners is essential before starting IVF. Male factors account for at least 30 to 50 percent of fertility issues in couples. 

Semen Analysis

The semen analysis is done on an ejaculated sample collected after masturbation. It is best to do this test after a patient has abstained from sexual activity for two to five days. The test can be inaccurate if there has been recent ejaculation (counts too low) or if ejaculation has not occurred in a long time (many dead sperm). At the laboratory, the sample is analysed for many different parameters, including fluid volume, sperm numbers, sperm motility (the percentage of moving sperm) and sperm morphology (the shape and appearance of the sperm). Variations can occur from test to test, even in the same man, and sometimes the test needs to be repeated.

Sperm Retrieval 

When a man has little to no sperm in his ejaculate, it may be possible to retrieve sperm from his testicles or epididymis. This is a procedure performed by a urologist. The sperm retrieved can be used immediately or frozen for future IVF cycles. 

What are the IVF insemination techniques? 

Within IVF, there are two different insemination techniques: standard insemination and intracytoplasmic sperm injection (ICSI) insemination.  

Standard insemination is a procedure in which the eggs retrieved are maintained within their cumulus complex and are combined with sperm in the same culture dish. Because their cumulus complex is maintained, egg quality and maturity cannot be evaluated.  

To perform ICSI insemination, the cumulus complex of the egg is removed and the egg maturity and quality are evaluated. Maturity of the oocyte is important as only mature eggs can fertilise. ICSI involves the insertion of a single sperm directly into the cytoplasm of a mature egg. It is typically recommended for patients in our centre.  

What does the IVF process involve? 

1. Ovarian stimulation: Fertility hormone medications are used to stimulate the ovaries to produce multiple mature eggs, maximising the chance of success. Throughout this phase, we monitor follicular development and hormone levels through transvaginal ultrasounds and blood tests every 2 to 3 days for about 10 to 16 days. 
   
2. Egg retrieval: Once the follicles are ready, we perform a minor transvaginal outpatient procedure to retrieve the eggs. This is done under general anaesthesia and typically takes about 30 minutes. 
   
3. Fertilisation: The retrieved eggs are fertilised with sperm at our state-of-the-art laboratory. This is done via standard insemination or ICSI insemination.  
   
4. Embryo development: Fertilised eggs are monitored as they develop into embryos over 3 to 5 days. Our embryologists assess each embryo daily to determine which are healthiest and most viable for transfer or for freezing. 
   
5. Embryo transfer: A selected embryo is carefully transferred into the womb using a thin catheter. This is a gentle, minimally invasive procedure that typically does not require anaesthesia. 
   
6. Pregnancy test: About 12 to14 days after the embryo transfer, a blood test to check for pregnancy is done at the Clinic for Human Reproduction (CHR). Our team will provide close support and guidance through the results, and offer advice on follow-up steps as part of your IVF journey in Singapore. 

What is the success rate of IVF?

The success rate is approximately 30-40%, which varies depending on factors such as age and the cause of infertility.  

Pre-implantation Genetic Testing (PGT) 

PGT is a technique used in conjunction with IVF to test embryos for genetic disorders prior to the transfer to the uterus. PGT makes it possible for couples with serious inherited disorders to decrease the risk of having an affected child.  

PGT is performed using a high-powered microscope. A single cell is removed from each embryo and tested for the genetic trait of interest. The unaffected embryos are identified, separated from the affected embryos for transfer into the uterus.  

NUH offers three types of PGT: 

• PGT for Monogenic/Single Gene Defects (PGT-M) 
• PGT for Chromosomal Structural Rearrangements (PGT-SR) 
• PGT for Aneuploidies (PGT-A)  
  

Not all couples require PGT. Couples will be referred to a genetics specialist prior to PGT for proper counselling. 

Click here for more information on PGT.

Assisted Hatching 

Assisted hatching is a technique where a small opening is created in the outer shell of the embryo (zona pellucida), which weakens the shell and improves the likelihood of successful hatching and embryo implantation. Indications for assisted hatching include advanced age, thick or pigmented zona, and previous IVF failures. This technique is typically performed with fresh multicell-stage embryos and all frozen embryos. 

Embryo Grading 

During IVF, the embryos are cultured for up to six days and receive quality grades each day. 

Day 0: Egg Retrieval and Insemination

Egg maturity is important because a mature egg has the best chance of being fertilised. There are three different stages of egg maturation: 

1. Germinal vesicle (GV): The egg has not begun meiosis yet, so it is considered immature. 
2. Mataphase I (MI): The egg is in the first phase of meiosis; however it is still not completely mature because it has not entered the second phase of meiosis. This kind of immature egg may mature after a couple of hours of temperature-controlled incubation.
3. Metaphase II (MII): The egg is in the second phase of meiosis and is mature. Eggs at this stage of maturity are ready for fertilisation.

Egg quality is graded on a good-fair-poor scale.

• Good
  • Clear cytoplasm / normal shape 
  • Single distinct polar body
  • Clear / thin zona pellucida
• Fair
  • Slightly grainy cytoplasm / misshapen
  • Fragmented / abnormal polar body
  • Slightly pigmented / amorphous zona
  • Cytoplasmic bodies
  • PV debris
• Poor
  • Dark / grainy cytoplasm / misshapen
  • >1 polar body structure
  • Vacuoles 
  • PV debris

Day 1: Fertilisation Check

Fertilisation can be seen 16 to 22 hours post insemination. Normal fertilization is identified by exactly two pronuclei in the centre of the single cell zygote. Fertilization is considered abnormal when there is only one pronucleus or when there are more than two pronuclei. 

Day 2/3: Multicell Grading

On day two, the single cell zygote should divide into an embryo (approx. two to four cells). On day three, the embryo should continue to divide (four to eight cells).

• Embryo quality:
  • Good: cells are symmetrical with clear cytoplasm
  • Fair: cells are slightly asymmetrical and/or have slight cytoplasmic irregularities
  • Poor: cells are significantly asymmetrical and/or have dark, grainy cytoplasm
• Fragmentation: little bits of cytoplasm that escape during cellular division and stay within the embryo. The ranges of fragmentation are listed below from least to most heavy. Fragmentation ranging from A to B is most preferred. 
  • A = No fragmentation
  • B = <10% mild fragmentation
  • C = 10-35% fragmentation
  • D = >35% fragmentation

Day 4

On day four, embryos begin transitioning from a multicell embryo to a more advanced developmental stage. Embryos should begin compacting and forming morulae. Cells of a morula-stage embryo are not as distinct as in previous days; therefore, these embryos do not receive quality grades. 

Day 5/6: Blastocyst stage

A blastocyst is a highly developed embryo that is composed of two different cell types: one group of cells, called the inner cell mass, leads to foetal tissue and another group of cells, called the trophectoderm, forms the placenta. Blastocysts are graded on their expansion (early, expanding, expanded, and hatching) as well as the quality of the two different cell types (graded on a good-fair-poor scale). Blastocysts that are good to fair quality meet freeze criteria. 

Fertility challenges can be emotionally demanding for individuals and couples. 

Support options include: 

• Counselling services 
• Fertility support groups 
  
• Mental health professionals 

Your healthcare team can guide you to appropriate resources.