By NUH Women's Centre


Difficulty Conceiving
Have you been trying to conceive without success? Please do not feel alone. Approximately one in six couples will have difficulty conceiving and may need medical help to identify the possible causes.


The good news is that there are many treatments available and getting started is the first step. Couples are generally advised to seek medical care through their obstetricians or a reproductive specialist. Your obstetricians can offer some initial tests or initial treatments and hopefully this will work. However, after three months of unsuccessful treatment, it is recommended that you seek consultation with a reproductive specialist.


When should I see a Specialist?
There are a number of ways for you to receive the treatment you need. One option is to start by speaking with your obstetrician or gynaecologist; another is to go directly to a reproductive specialist. Both physicians will perform initial tests to assist in identifying potential causes of your infertility.


As a woman's fertility naturally decreases with age, starting in her late 20s and dropping more rapidly after 35 years old, and fertility success follows the same pattern, you should not wait too long before seeking consultation with a specialist.


Treatment Options

  •  IUI: Intrauterine Insemination
  •  IVF: In-Vitro Fertilisation
  •  Egg Donation and IVF
  •  Male Infertility Treatment
  •  Laboratory Procedure

IUI: Intrauterine Insemination
Intrauterine insemination (IUI) is a fertility procedure in which sperms are washed, concentrated, and injected directly into a woman's uterus. The most common indications for IUI are cervical mucus abnormalities, low sperm count, low percentage of sperms moving , increased sperm viscosity or antisperm antibodies, unexplained infertility, and the need to use frozen donor sperm. In natural intercourse, only a fraction of the sperm makes it past the woman's cervical mucus into the uterus. IUI increases the number of sperm in the fallopian tubes, where fertilisation takes place.


Studies show that IUI is most successful when it is coupled with fertility drugs that recruit multiple follicles. This technique often is called controlled ovarian stimulation and IUI.


IUI sometimes is recommended for couples with unspecified infertility and have been trying to have a baby for six to twelve months. You should have a thorough infertility evaluation before trying IUI.


Male Partner Requirements for IUI

IUI relies on the natural ability of sperm to fertilise an egg in the fallopian tubes. Studies show that IUI will not be effective in cases where the male has low sperm counts or poor sperm shape (also known as sperm morphology). Sperm tests are required, therefore, in order to indicate:

  •  Sperm count (number of sperm per cc)
  •  Sperm motility (percentage of sperm moving)
  •  Sperm morphology (shape)

Female Patient Requirements for IUI

The patient should have normal day three blood test results, open fallopian tubes, and a normal uterine cavity.

  •  Women with ovulatory disorders can be candidates for IUI if they respond adequately to fertility drugs. In these cases, hormone treatments stimulate follicle growth and the IUI is timed to take place after ovulation is induced. Hormone treatments are usually used even for women without ovulatory disorder.
  •  Women with mild endometriosis may benefit from IUI if they do not have a distortion of the pelvic structures.
  •  Women with severely damaged or blocked fallopian tubes are not suitable for IUI.

IUI Procedures

IUI is timed as closely to ovulation as possible, therefore you will be monitoring your cycle with an timing ovulation scan and/or we will control the time of ovulation with hCG. The insemination is accomplished by placing a speculum in the vagina to visualize the cervix in a procedure position similar to a pap smear. A small, sterile catheter containing the sperm will be inserted through the cervical opening into the uterine cavity next to the tubal openings. Depending on which type of treatment you are doing, a second sample of sperm is placed in the cervix. Some women may experience mild cramping. You may experience some spotting or light bleeding after the insemination, which is normal; however do avoid all strenuous exercise on the day of your insemination.


Doctors might try three cycles of IUI, and if these are not successful, they may recommend more advanced methods such as in-vitro fertilisation (IVF). Unlike IVF, IUI does not involve egg collection or IV sedation.


IVF: In-Vitro Fertilisation
In-vitro fertilisation (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 recipient's uterus at a multicell embryo stage or later at the blastocyst embryo stage. All procedures required during an IVF cycle, including ovarian stimulation and monitoring, egg retrieval, and embryo transfer, are performed on-site.


Egg Donation
This is key to conception when a woman cannot produce her own eggs. Centres such as The Clinic For Human Reproduction at NUH Women's Centre, provides an egg donor programme and IVF treatment which meeting the criteria set forth by the Ministry of Health.


For donor egg IVF, an egg donor recipient may select an egg donor who is a sister, close friend, or relative of the recipient's. Donor egg IVF successfully treats women who are carriers of genetic diseases, women who have had multiple failed cycles of IVF, women with impaired ovarian function, or healthy older women. This IVF treatment also heightens the chance of pregnancy for women whose attempts at IVF have revealed a poor response to fertility medications or whose eggs did not fertilise well or form viable embryos.


As part of the IVF egg donation programme protocol, an egg donor injects fertility medication to stimulate her ovaries to produce multiple eggs. Hormone replacement is used to synchronise the recipient to the egg donor cycle. Just prior to ovulation, using standard IVF techniques, the eggs are retrieved from the egg donor's ovaries and fertilised with sperm from the recipient couple.


Male Infertility Treatment
The importance of a thorough evaluation of both partners in the relationship cannot be overestimated. Male factors account for at least 30 to 50 percent of all fertility issues in patients.


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). Once the sample has been taken to the laboratory, it is analysed for many different parameters, including fluid volume, sperm numbers, sperm motility, and sperm morphology. 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 an urologist. The sperm retrieved can either be frozen for future use or used immediately for an IVF cycle.


Laboratory Procedure
ICSI: Intracytoplasmic Sperm Injection
Within IVF, there are two different insemination techniques: standard insemination and 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. As their cumulus complex is maintained, egg quality and maturity cannot be evaluated.


In order to perform ICSI insemination, the cumulus complex (made up of cumulus cells) of the egg is removed and the egg maturity and quality are evaluated. Maturity of the oocyte is important because only mature eggs have the opportunity to fertilise. ICSI involves the insertion of a single sperm directly into the cytoplasm of a mature egg.


PGD: Pre-implantation Genetic Diagnosis
Pre-implantation genetic diagnosis (PGD) is a technique that can be used in conjunction with IVF to test embryos for genetic disorders prior to their transfer to the uterus. PGD makes it possible for couples with serious inherited disorders to decrease the risk of having an affected child. PGD can also be considered for couples experiencing repeat pregnancy loss due to genetic disorders, and couples who already have one child with a genetic disorder and are at high risk of having another.


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


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 Zero - 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:

  • Germinal vesicle (GV): The egg has not begun meiosis (a process of cell division that produces reproductive cells known as gametes), yet, so it is considered immature.
  • Metaphase 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.
  • 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

o Clear cytoplasm/normal shape
o Single distinct polar body
o Clear/thin zona pellucida

  • Fair

o Slightly grainy cytoplasm/misshapen
o Fragmented/abnormal polar body
o Slightly pigmented/amorphous zona
o Cytoplasmic bodies
o PV debris

  • Poor

o Dark/grainy cytoplasm/misshapen
o >1 polar body structure
o Pigmented/thickened zona
o Vacuoles
o PV debris


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


Day Two/Three - 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).


Day Four
On day four, embryos begin their transition 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 Five/Six - 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 fetal tissue and another group of cells, called the trophoectoderm, 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 Preservation
Oocyte cryopreservation, or egg freezing, is a relatively new procedure in the field of assisted reproductive technologies. Overall, this technology increases a woman's potential to have children later in life. Since the first successful pregnancy using egg freezing was reported in 1986, approximately 600 babies have been born. Currently, pregnancy rates are between 30 and 40 percent.


  • Egg Freezing

Egg freezing allows a woman to preserve her fertility until she is ready to start her family. During an egg-freezing cycle, a patient will go through many of the same steps that are involved in a typical IVF cycle: ovulation stimulation, ultrasound monitoring, and egg retrieval. After egg retrieval, the eggs will be cultured for a few hours and then frozen the same day for future use.


  • Embryo Freezing

Embryo freezing is a technique that is recommended when high-quality embryos remain after embryo transfer. These embryos remain frozen until the patient is ready to use them. If patients have completed their families, they have the option to donate these frozen embryos to research, another couple, or training; the embryos can also be discarded.



For more information, please contact the Women's Clinic at (65) 6772 2255 / 2277, or email us at Womens_Clinic@nuhs.edu.sg

This featured article is contributed by the NUH Women’s Centre, National University Hospital.


Please visit www.nuhgynae.com.sg to read more.

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