Reproductive Medicine and Maternal Health

In Canada, it’s estimated that 1 in 6 couples has trouble having a baby.

Why? The hormones responsible for controlling our reproductive systems and cycles must be produced in the right amounts, in the right sequence and at the right time for ovulation and sperm production to occur. Various physical or structural problems such as tubal disease or sperm problems can also affect the ability to conceive.

At Ferring, the treatment of infertility is one of our key areas of expertise. It includes a number of proven hormonal therapies that can correct hormonal imbalances and stimulate ovulation. With these and other procedures, infertile couples now have a better chance of conceiving than ever before.

Important Safety Information on BRAVELLE™ and Recalled lots due to Reduced Therapeutic Effect

Physical and emotional burden

Infertility is more than just a physical problem. While many couples treated for infertility eventually experience the joy of having children, infertility and its treatment generally places a considerable amount of stress on couples' relationships and personal lives. The successful management of infertility includes both the physical and emotional care of the couple.

To learn more about management of infertility, please view this guide (PDF):

A guide to managing infertility.pdf 

Normal functioning of the male and female reproductive systems depends on complex hormonal communication signals between the endocrine system and the sexual organs: ovaries in women and testes in men.

Role of hormones
Like most of the body's systems, hormones direct the intricate processes involved in male and female fertility.

Three key hormones are responsible for controlling the reproductive systems and cycles in both sexes. The Gonadotropin-Releasing Hormone (GnRH) is secreted by the hypothalamus. This hormone stimulates the secretion of two gonadotropin hormones from the pituitary gland: the Luteinising Hormone (LH) and the Follicle Stimulating Hormone (FSH). The LH and the FSH are key elements behind ovulation and development of sperm cells in men.

The body must produce these hormones in the right amounts, in the right sequence and at the right time for ovulation and sperm production to occur. If not, the chances of conception will be reduced.

Women's reproductive system

Producing fertile eggs (oocytes)
Women are born with about 400,000 immature eggs already in their ovaries. Each month, between puberty and menopause, one egg (usually) fully matures and starts its journey down the fallopian tubes in the anticipation of fertilisation.

Menstrual cycle
There are three stages to a woman's "monthly" menstrual cycle. On average, this cycle lasts 28 days.

• Stage one: follicular phase
  The first stage of the cycle lasts for about two weeks. During this stage, the secretion of FSH rises, stimulating the development of an egg-containing follicle and the maturation of the egg within it.
  
  The growing follicle secretes increasing amounts of the female hormone, oestrogen, which triggers changes in the lining of uterus (endometrium) and cervical mucus. The cervical mucus thins to allow sperm to pass through and the endometrium thickens making it ideal for the implantation of a fertilised egg.
  
• Stage two: Ovulation
  About 32 hours before an egg is ready to be released, the amount of oestrogen produced by the follicle sharply increases, causing a spike in the secretion of LH by the pituitary gland. This surge in LH production causes ovulation. The matured egg bursts out of the follicle and travels down the fallopian tube. 
  
• Stage three: luteal phase
  The remains of the follicle become a corpus luteum, which secretes a second female hormone, progesterone. This helps maintain the best conditions for pregnancy should the egg be fertilised. 
  
  If the egg is not fertilised within about 72 hours, the corpus luteum eventually degenerates and the egg is expelled from the uterus along with the lining, leading to menstruation approximately 14 days later.

Men's reproductive system

Sperm production
LH is responsible for the production of the male hormone testosterone, which along with FSH is responsible for stimulating sperm production in the testicles.

Sperm production, spermatogenesis, is a continuous process. It takes about 72 to 74 days for a male "germ" cell to develop into an active sperm. Several hundred million sperm are produced on a daily basis. From the millions of sperm cells available each day, only a small proportion has full fertilising potential.

Spermatogenesis is most efficient at a temperature of 34°C. It is vulnerable to increases in temperature.

Sperm cells
A sperm cell consists of two main parts:

• the head which has the crucial role of clinging to an egg and penetrating its outer membrane, taking with it its genetic information
• the tail, which enables the sperm cell to "swim" the length of the female reproductive tract to reach an egg.

Problems affecting any of these components will affect the fertilising power of the sperm cell.

Best time for conception
Becoming pregnant is not always straightforward even for people without fertility problems. Humans are one of the least fertile creatures on earth, with only a 25 percent chance of conception each month.

Sperm can only live for around 48 hours in the female reproductive tract and the egg needs to be fertilised within 72 hours following ovulation, leaving a narrow window for fertilisation. Thus, the best time for conception is around the middle of the menstrual cycle just before ovulation occurs.

Pregnancy

Under normal circumstances only a few hundred of the 14 million sperm deposited naturally into the vagina during intercourse are able to reach the end of the fallopian tube where the egg can be fertilised.

After one sperm has successfully fertilised an egg, cell division begins and the fused cells become an embryo. Migration of the embryo happens at the same time and about a week following ovulation, the embryo finds itself in the uterus and implants itself into the endometrium. Successful implantation prevents the corpus luteum and endometrium from breaking down, therefore menstruation does not happen.

At this point, a third gonadotropin, the human chorionic gonadotropin (hCG), is produced by the placenta which develops upon implantation. The hCG plays an important role in maintaining the pregnancy. It stimulates the corpus luteum to continue to produce high levels of oestrogen and progesterone.

The complex nature of the processes and interactions involved in egg/sperm production and fertilisation means that something can go wrong at various stages of the process.

Infertility
Infertility is usually defined as the inability of a couple to conceive after one year of unprotected intercourse. However, younger couples may be encouraged to wait for up to two years by some doctors before seeking treatment, while women over 35 or those with certain medical conditions, such as diabetes, should only wait six months.

Statistics
About one in six couples concerned end up seeking help. Within this group, the cause of infertility is found to lie with the woman in up to 40 per cent of cases and with the man about 30 per cent of the time. In the remaining cases, either both partners are found to have reduced fertility or the cause cannot be determined.

Female factors

• Hormonal / ovulation: Hormonal problems affect follicular development as well as ovulation. Problems with ovulation are the most common cause for female infertility and account for up to a third of all cases.
     
• Tubal problems: Damage to the fallopian tubes is another common reason for infertility, preventing the egg from travelling down, affecting fertilisation or passage to the uterus.
     
• Uterine problems: Endometriosis can be a key problem in the uterus. In this condition, developing cells from the endometrium break away and stick to the ovaries and fallopian tubes affecting the way they function. Fibroids and polyps in the uterus can also cause problems with fertility.
     
• Cervix / vaginal problems: Structural abnormalities of the vagina or cervix can affect fertility as can the physical characteristics of the cervical mucus. The mucus can be hostile to sperm, perhaps containing antibodies or thick enough to block the movement of the sperm.
     

• Hyperprolactinaemia: This is a condition where excess levels of the hormone prolactin are found in the blood. This can cause symptoms including irregular or absent menstrual cycles, infertility and increased production of breast milk.

Male factors

• Sperm potency: The vast majority of cases of male infertility are due to a low sperm count, which is generally associated with a high rate of sperm defects (size, shape and movement).
     
• Hormonal imbalances: Hormonal imbalances related to FSH and LH do occur in men but are not very common.
     
• Testicular failure: Some men are found to have no sperm in their semen. This could be due to a failure to ejaculate or a failure of the testes to produce sperm.
     
• Varicocele: These are varicose veins in one or both scrotums, and are the most common anatomical abnormality in infertile men.
     
• Tubal blockage: Damage as a result of infections can prevent the sperm from getting into the semen. Occasionally the ejaculate of some men is diverted into the bladder.
     
• Sperm antibodies: A small group of men actually produce antibodies against their own sperm. This cause accounts for around 10 per cent of unexplained male infertility.   

Joint infertility problems

Of the number of cases of infertility where the problem lies with both partners, some of the causes may be straightforward and quite simple to remedy. As the window of opportunity to fertilise an egg is quite limited in a woman's monthly cycle, the frequency and timing of intercourse may be factors. Some cases have been found to be related to technique (the sperm is not deposited high enough in the vagina). Fertility is also reduced with increasing age, especially in women. In men, testosterone levels can decline with age but not in the dramatic manner seen in women. Men continue to produce sperm but their motility and quality are reduced with advancing age.

Treating Infertility

A variety of options are now available to help identify the cause(s) of infertility and ultimately provide couples with the highest chance of realising their dream of having a baby.

Ferring has been helping couples to conceive for more than a decade with a portfolio of high quality products that work in the same way as the body's natural hormones. By correcting hormonal imbalances and stimulating ovulation, these products help to achieve a high pregnancy success rate.

Treatment options
The procedures and treatments available from infertility clinics can be divided into four main categories:

• Hormonal and anti-oestrogen therapy (includes induction of ovulation)
   
• Artificial insemination (AI) procedures
   
• Surgery
   
• Assisted reproductive technology (ART)

The infertility specialist is likely to start with the simplest treatment that is suitable for the cause of infertility in a particular couple. Where a pregnancy is not achieved after a few cycles of treatment another procedure will be selected. Between 85% and 90% of infertility cases are treated with conventional medical therapies such as medication or surgery.

Hormonal therapy
Its objective is to replace, or enhance, the hormones produced naturally by the body. Gonadotropin treatment is also used to stimulate "super-ovulation" for assisted conception procedures, including in-vitro fertilisation (IVF).

Ovulation induction
Ovulation induction can be used as a treatment on its own or in combination with another infertility treatment such as artificial insemination or IVF.

The treatment stimulates ovulation in women with infrequent or irregular periods, or in those whose menstrual cycles have stopped due to polycystic ovaries. Although successful for many women, they carry a high risk of multiple pregnancies.

Artificial insemination
Most often used in cases of infertility due to low sperm count or reduced motility, the procedure can also be used in cases where the woman has hostile cervical mucus, or produces antibodies against sperm. The sperm cells are collected, processed and washed and then inserted directly into the uterus, cervical canal or vagina.

Surgery
Surgery can be used to correct anatomical abnormalities of the reproductive system in either the woman or the man.

Assisted Reproductive Technology
ART is a general term covering a range of advanced procedures, including micro-manipulation of sperm, to aid fertilisation and implantation. The procedures all have one thing in common: they require the collection of multiple mature eggs (oocytes), which is achieved by hormonal stimulation of the ovaries often described as "super-ovulation".

The main ART procedures include:

• In-vitro fertilisation (IVF)
   
• Intracytoplasmic sperm injection (ICSI) - for male infertility
   
• Gamete intrafallopian tube transfer (GIFT)
   
• Zygote intrafallopian transfer (ZIFT)
   
• Blastocyst transfer (BT)

Obstetrics is the branch of medicine related to pregnancy and giving birth. Most women have uneventful pregnancies with no complications, but some pregnancies will require further care and attention. Part of obstetric care is to try to identify and prevent problems occurring during pregnancy and labour that could affect the health of both mother and unborn baby.

To learn more, please select one of the below topics:

• Induction of labour
   
• Pre-term labour
   
• Post partum haemorrhage
   

Labour is initiated or induced by obstetricians in situations where it is considered safer, for the mother or the unborn child, for the baby to be delivered.

Reasons for induction include:

• pre-eclampsia (sudden, severe rise in blood pressure and kidney impairment)

• poor growth in the baby

• unexplained bleeding in the last phase of pregnancy

• a prolonged pregnancy (the most common reason)

After 42-43 weeks of pregnancy most doctors agree that the baby is more likely to experience problems, with an increased risk of death or brain damage, if the pregnancy were to continue. Therefore labour is normally induced at around 42 weeks if it has not already occurred naturally.

Giving birth

Childbirth can be divided into three main stages:

• Stage 1: onset of labour, this stage prepares and opens the cervix for the baby to pass through

• Stage 2: delivery, actual birth of the baby

• Stage 3: passing of the placenta

Oxytocin and prostaglandins are the main substances produced at the end of a pregnancy to initiate the key processes for labour and birth.

Oxytocin is the hormone that drives the uterus to contract, pushing the baby down towards the cervix. While the release of prostaglandins sets in motion the processes that soften the cervix, making it thinner, and encouraging it to open ready for the baby to pass through, prostaglandins also make the uterus more sensitive to oxytocin.

As soon as the baby is born, the uterus continues to contract to expel the placenta and return to its pre-pregnant state as soon as possible. After the placenta is delivered the uterus should contract and become firm.

Normally defined as labour occurring before 37 weeks of pregnancy, pre-term, or premature labour usually poses little risk for the mother but the negative health consequences for the baby can be vast.

Globally, it is estimated that 13 million babies are born prematurely each year. Premature, or pre-term, birth is one of the most common causes of death and disability in infants. The underlying causes are unknown in most cases.

All sorts of techniques have been tried to halt a labour that has started too early. Most treatments involve the use of medications called tocolytic agents that are designed to stop the contractions of the uterus. They are particularly useful at postponing delivery, giving the baby a chance to mature further or to enable the mother to reach a hospital with specialist facilities.

Premature birth can be classified in one of three categories according to the gestational age:

About a third or more cases of pre-term labour occur for no apparent reason, though experience has shown that some groups of women are more likely than others to be at a higher risk.

Risk factors
Very young women, older women (in their 40s), women who have had frequent pregnancies, those who are carrying more than one baby, women who are underweight or have a poor diet and those who smoke are all known to be at risk of premature deliveries.

Other cases of pre-term labour are associated with medical ailments. A condition known as pre-eclampsia is behind a third of all premature births. Pre-eclampsia creates a sudden and severe rise in blood pressure and is directly linked to pregnancy, affecting about 1 in 14 pregnant mothers.

An incompetent cervix, one that is weak and unable to remain closed under the weight of a growing baby, can also lead to a premature delivery, as can many vaginal infections. Also, stressful events may cause a woman to go into labour before full term is reached.

A short interval between pregnancies (less than 6 months), as well as multiple pregnancies, increase the risk of pre-term labour. 60 per cent of twins are born pre-term.

Potential risk to the baby
Premature babies are small and underdeveloped. They are at risk of death and a range of complications. The earlier they arrive (thus the smaller they are), the higher the risks of these consequences. The degree of prematurity is also linked to long-term development problems of the child. Babies born prematurely have higher rates of learning disabilities, cerebral palsy, sensory deficits and respiratory illnesses compared to babies born at term.

Babies born after only 23 to 24 weeks of pregnancy are at most risk of both short and long-term problems. Babies born after 34 weeks usually only have a low risk of problems because their systems have almost completely matured.

So it is important to maintain the pregnancy as long as possible to give the newborn baby the best chance in life as possible.

Diagnostic of pre-term labour
The World Health Organization (WHO) defines pre-term birth as being born before 37 weeks of gestation.

Pre-term labour is diagnosed when there are painful, palpable contractions lasting more than 30 seconds and occurring every 5 minutes, and when there is evidence of a change in the position, consistency, length and/or dilation of the cervix.

There are two methods to help determine if pre-term labour is occurring:

• measurement of cervical length (the shorter the length, the higher the risk of imminent birth)
• determination of fetal fibronectin (fFN) levels in the vagina. The lower the amount of fFN in the vagina, the lower is the risk of pre-term birth.

Treating pre-term labour
Tocolytic agents delay labour by preventing uterine contractions (tocolysis), thus allowing extra time for the baby to mature. Tocolysis improves clinical outcomes and reduces the length of stay at the hospitals for babies born prematurely.

Haemorrhage after delivery, or postpartum haemorrhage, is the loss of greater than 500ml of blood following vaginal delivery, or 1000ml of blood following cesarean section. It is the most common cause of perinatal maternal death in the developed world and is a major cause of maternal morbidity worldwide.

Uterine atony (inability of the uterus to contract), which leads to excessive bleeding, is responsible for 80 per cent of the cases. Retained placenta and infection can lead to the inability of the uterus to regain sufficient muscle tone.

A menstrual period usually lasts 3 to 5 days but anywhere from 2 to 8 days is considered normal. The average blood loss during menstruation is 35ml (with 10-80ml considered normal), although the impact of the loss on the patient's lifestyle and quality of life is of perhaps greater relevance.

In general, bleeding during menstrual periods is considered too heavy if:

• there is a need to change sanitary pads or tampon every hour for several hours
• there is a need to use double sanitary protection to manage menstrual bleeding
• there is a need to change sanitary protection during the night
• menstrual bleeding includes large blood clots
• heavy monthly bleeding interferes with regular activities
• the woman feels tired, lacks energy or has shortness of breath, which could be symptoms of anemia (a condition affecting red blood cells) caused by menstrual blood loss

Heavy Monthly Bleeding (HMB) is a medical condition that can be treated.

Causes of Heavy Monthly Bleeding

Heavy Monthly Bleeding can have a lot of different causes. Some of the possible causes of HMB include:

• Non-cancerous tissue growths in the uterus (fibroids or polyps)
• Bleeding disorders such as von Willebrand disease, which affects the blood's ability to clot
• Conditions in which pieces of the lining of the uterus grow outside the uterus, or into the muscle of the uterus (endometriosis or adenomyosis)
• High levels of certain chemicals in the body (prostaglandins or endothelins)
• Infections such as pelvic inflammatory disease (PID)
• Imbalance of hormones in the body
• Intrauterine devices (IUDs) used for birth control
• Liver, kidney or thyroid conditions

Much of the time, a cause for HMB cannot be found. But the heavy bleeding during monthly periods can still be treated.

For Professionals
The following links are physician-oriented websites only.

Infertility

OBGYN.net
Provides information and educational materials

Fertility and Sterility
The Official Journal of the American Society for Reproductive Medicine

Association of Reproductive Health Professionals (ARHP)

European Society of Human Reproduction and Embryology (ESHRE)

Obstetrics

EJOG - Obstetrics & Gynecology
Latest research affecting clinical practice in all the subspecialist areas of OB/GYN

March of dimes
Working together for stronger, healthier babies

EFCNI
European Foundation for the Care of Newborn Infants

For Patients
The following links are meant for patients.

Infertility

First Visit IVF

IHR - Infertility Resources

The Women's Surgery Group

EndometriosisZone

Obstetrics

Women's health

Preemie-L
Parents of Premature Babies Inc.

AWHONN
Association of Women's Health, Obstetric, and Neonatal Nurses, Preterm Labor

Eumom.com
The Pregnancy Resource

Please note that Ferring cannot accept liability for the content of those sites not managed or controlled by Ferring.