Dr. Lester De Silva asked:


Background

Definition of unexplained infertility: Infertility cases in which the standard infertility testing has not found a cause for the failure to conceive.

The definition of what “standard testing” consists of is not agreed upon by all experts. Unexplained infertility is also referred to as idiopathic infertility. Medical studies have reported that 0-26% of infertile couples have unexplained infertility. The most commonly reported figures are between 10-20% of infertile couples. However, those percentages are from studies in which all the women had laparoscopy surgery to investigate the no longer done as part of the routine fertility workup. Therefore, we are not finding all of the causes of infertility that we used to – leaving more couples in the unexplained category. The current rate of unexplained infertility is probably about 50% for couples with a female partner under age 35 and about 80% by age 40 (see discussion below about female age issues).

In reality, there are probably hundreds of “causes” of infertility. What this means is that there are a lot of things that have to happen perfectly in order to conceive and have a baby. As a simplified example:

The hormones that stimulate egg development must be made in the brain and pituitary and be released properly The egg must be of sufficient quality and be chromosomally normal The egg must develop to maturity The brain must release a sufficient surge of the LH hormone to stimulate final maturation of the egg The follicle must rupture and release the follicular fluid and the egg The tube must “pick up” the egg The ***** must survive their brief visit in the vagina, enter the cervical mucous, swim to the fallopian tube and “find” the egg The ***** must be able to get through the cumulus cells around the egg and bind the shell (zona pellucida) of the egg The ***** must undergo a biochemical reaction and release their DNA package (23 chromosomes) into the egg The fertilized egg must be able to divide   The early embryo must continue to divide and develop normally After 3 days, the tube should have transported the embryo into the uterus The embryo must continue to develop into a blastocyst The blastocyst must hatch from its shell The endometrial lining of the uterus must be properly developed and receptive  The hatched blastocyst must attach to the endometrial lining and “implant” Many more miracles in early embryonic and fetal development must then follow…

 A weak link anywhere in chain can this cause failure to conceive

The above list is very oversimplified, but the point is made. There are literally hundreds of molecular and biochemical events that have to function properly in order to have a pregnancy develop. The standard tests for infertility barely scratch the surface and are really only looking for very obvious factors, such as blocked tubes, abnormal ***** counts, ovulation regularity, etc. These tests do not address the molecular issues at all. That is still for the future…2

The subtle causes of sub fertility that have been proposed as underlying unexplained infertility are as follows3

Ovarian and endocrine factors

 Abnormal follicle growth

Luteinized unruptured follicles and ovarian cysts

Hyper secretion of LH

Hypersecretion of prolactin in the presence of ovulation

Reduced growth hormone secretion /sensitivity

Cytological abnormalities in oocytes

Genetic abnormalities in oocytes

Antibodies to zona pellucida

  Peritoneal factors

 Altered macrophage and immune activity

Mild endometriosis

Antichlaydial Ab

  Tubal factors

 Abnormal peristalsis or cilliac activity

Altered macrophage and immune activity

  Endometrial factors

 Abnormal secretion of endometrial proteins

Abnormal intergrin/adhesion molecules

Abnormal t cell and natural killer cell activity

Secretion of embryo toxic factors

Abnormalities in uterine perfusion

 Cervical factors

 Altered cervical mucous

Increased immunogenicity

General immune factors

Altered cell mediated immunity

  Male factors

 Reduction in motility, acrosome reaction, oocyte  binding ,and zona penetration

Ultrasructural abnormalities of head morphology

  Embryological factors

 Poor quality embryos

Reduced progression to blastocyst

Abnormal chromosomal complement-increased miscarriage rate

Unexplained infertility and female age

Women are born with certain number of eggs and when they attain menarche they start releasing these eggs cyclically. As the woman ages they run out of there eggs and quality of eggs will become poorer too. Therefore the likelihood of a diagnosis of unexplained infertility is increased substantially in women 35 and over – and greatly increased in women over 38. Since we do not have a “standard category” called egg factor infertility, these couples sometimes get lumped in to the “unexplained” infertility category. Most women over 40 who try to get pregnant will have difficulty, and fertility over age 44 is rare – even in women who are ovulating regularly every month. The point is that the older the female partner, the more likely that there is an egg related issue causing the fertility problem. Unfortunately, there is currently no specific test for “egg quality”.2

Unexplained infertility and Mild endometriosis

It is not quite clear whether mild endometriosis causes infertility and treating mild endometriosis improve the fertility rates. Some recent studies has shown surgical treatment for mild endometriosis increases the fertility. Some experts would also consider infertility associated with mild endometriosis to be in the “unexplained” category. This is because a cause and effect relationship has not been definitely established between mild endometriosis and fertility problems.

Chance for getting pregnant on own – without fertility treatment – for couples with unexplained infertility

The duration of infertility is important. The longer the infertility, the less likely the couple is to conceive on their own. After 5 years of infertility, a couple with unexplained infertility has less than a 10% chance for success on their own.

One study showed that for couples with unexplained infertility and over 3 years of trying on their own, the cumulative pregnancy rate after 24 months of attempting conception without any treatment was 28%. This number was found to be reduced by 10% for each year that the female is over 31.4

Treatment options for unexplained infertility

Ovarian stimulation and/or intrauterine insemination (IUI)

Intrauterine insemination vs. timed *********** – no medications involved

Studies have been shown that chances of pregnancy is increased with intrauterine insemination  compared to timed ***********.

Clomid and timed intercourse

Glazener et al .treated 100women,43% of whom were porous ,with either clomid 100mg from days 2-6 and placebo in a randomized cross over study. Overall there was a 50% increase in pregnancy rates after 3 cycles of treatment. Benefit was seen in after 3 years of infertility and more so in parous women.The same study showed that there were no conception in women over 35 years.5 This suggest that these women are not suitable candidates for clomid treatment and should be treated vigorously with assisted conception methods.

Clomid plus IUI

Treatment with Clomid tablets plus IUI improves fertility rates. For unexplained infertility, studies have shown that for women under 35, monthly success rates for Clomid plus insemination are about 10% per cycle. This pregnancy rate holds up for about 3 tries and the success rate is considerably lower after that.

Deaton et al carried out a randomized study between timed *********** or clomid with IUI, and showed that monthly fecundity was 9.5% in clomid plus IUI group compared to control group- a significant difference.6  In the same study it has been showed that there was no difference in number of follicles between conception and non conception cycles, suggesting that the insemination component have a more important influence than the Clomid does on outcome- but success rates are higher when both are used together.

Collating all studies together a recent systematic review, Hughes et al. reported that treatment with clomid is superior to no treatment or placebo (95% CI 1.5-4.65).7

Injectable gonadotropins plus intercourse

This is less extensively studied. However a study by Mascarenhas et al demonstrated that super ovulation with gonadotrophins significantly increased the pregnancy rates in unexplained infertility.8

Injectable gonadotropins (shots of FSH hormone) plus IUI

Several studies showed improved pregnancy success rates with injectable FSH plus IUI treatment as compared to no treatment. A meta-analysis by Hughes9 indicated that FSH plus IUI increases the pregnancy rate by 2.3 times than compared to FSH plus timed ***********.

It is most likely that super ovulation and IUI  both independently increase fertility potential, with relatively more fertility benefit coming from the IUI component.

Assisted reproductive technologies

IVF

In vitro fertilization (IVF) has high success in young women with normal ovarian reserve (normal FSH levels) and unexplained infertility. Most couples with unexplained infertility with a female partner under age of 35 could try about 3 artificial inseminations and if fail to pregnant  it is sensible to have IVF. On the other hand women over 35 years should have been offered IVF as a first line treatment.

GIFT

Gamate intrafallopian transfer goes one step further than superovulation/IUI as it involves the collection of oocytes and ***** into fallopian tubes. The main disadvantage compared to IUI is the need of laparoscopy and more complicated ovarian stimulation regimes. Compared with GIFT the main advantages of IVF are, that being able to study the fertilization, gives the opportunity to transfer best quality embryos to the uterus, and it also gives couple with surplus fertilized oocytes which can be cryo preserved for future use.

A large multi-center randomized study performed by European Society of Human Reproductive and Emryology to compare five treatments for unexplained fertility .The study concluded that there was no significant difference in outcome between them.(super ovulation 15% per cycle, super ovulation 27%,superovulation/IUI 27%,GIFT28%,IVF26%.10

 In summary, strategic management of unexplained infertility should focus on the efficacy of the method ,cost effectiveness and invasiveness of the procedures involved. Evidence suggest that there would be little or no benefit if treatment start in  a woman less than 35 years. Therefore it is worth considering superovulation and/or IUI for 3 cycles after 3 years of infertility, and if not successful go for IVF. However for older women (over 35) to consider IVF straight away.

References

1. Hull MGR, Glazener CMA, Kelly NJ et al.(1985), Population study of causes,

2. Unexplained Infertility

http ;//www.advancedfertility.com/unexplain.ntm( accessed 11/03/2008).

3. Adam, H.B. & Howard, S.J, (2003), Infertility In Practice, Churchill Livingstone, London.

4. Collings JA ( 1989), Natural course of unexplained infertility, Proceedings of the Serono symposium on unexplained infertility : basic and clinical aspects. Serono Aries Publishers, Rome.

5. Glazener CMA, Coulson C, Lambert PA et al, ( 1990), Clomiphene treatement for women with unexplained infertility : placebo-controlled study of hormonal responses and conception rates. Gynecol Endocrinol 4: 75-83

6. Deaton JL, Gibson M, Blackmer KM, Nakajima ST, Badger GJ & Brumsted JR, (1990), A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertil Steril 54 : 1083- 1088.

7. Hughes E, Collins J, & Vandekerchhove P (2002),Clomiphene citrate for unexplaine subfertility in women. Cochrane Database of systematic Reviews, Issue 1, 2002.

8. Mascarenhas L, Khastgir G, Davies WAR & Lee S, ( 1994),Superovulation and timed intercourse: can it provide a reasonable alternative  for those unable to afford assisted conception ? Hum Reprod  9: 67 -70

9. Hughes EG (1997), The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility : a meta-analysis. Hum Reprod 12 : 1865-1872

10. Crosignani PG, Walters DE & Soliani A, (1991), ESHERE multicentre trail on the treatment of unexplained infertility : a preliminary report. Hum Reprod 6: 953-958.



Alice

Alien asked:


Infertility is usually defined as not being able to get pregnant despite trying for one year. A broader view of infertility includes not being able to carry a pregnancy to term.

Problems with ovulation account for most infertility in women. Signs of problems with ovulation include irregular menstrual periods or no periods. Simple lifestyle factors, including stress, diet, or athletic training can affect a woman’s hormonal balance.

Many women trying to conceive for the first time panic if their periods continue for even three or four months. But the standard definition of infertility is unsuccessful conception after an entire year of unprotected intercourse

What is the cause of female infertility?

Infertility is a situation faced by many couples worldwide when they are unable to conceive. According to a survey in America, around 10% of couples bear the brunt of infertility. Usually when a couple is not able to conceive, the female partner is generally blamed, but the reality is that both the partners are equally responsible.

The most common cause of female infertility is an ovulation disorder. Other causes of female infertility include blocked fallopian tubes, polycystic ovary syndrome (PCOS) and endometriosis. Repeated miscarriages may be caused by congenital anomalies (birth defects) involving the structure of the uterus and uterine fibroids.

Signs and symptoms

The main symptom of infertility is the inability for a couple to get pregnant. There may be no other obvious symptoms of infertility.

In some cases, an infertile woman may have abnormal menstrual periods. An infertile man may have some signs of hormonal problems such as changes in hair growth or sexual function.

Diagnosis methods

Investigating suspected infertility requires a number of tests for both the woman and her partner. Tests for the woman may include:

* Blood tests – to check for the presence of ovulation hormones.

* Laparoscopy – a ‘keyhole’ surgical procedure in which an instrument is inserted though a small incision in the abdomen so that the reproductive organs can be examined.

* Ultrasound tests – to check for the presence of fibroids.

Treatment

The treatment of infertility has made enormous progress in the last decade as a result of advances in assisted reproductive technology, or ART. This technology combines the use of fertility drugs – hormonal therapy – with artificial insemination using any of a group of techniques: intrauterine insemination (IUI), in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), or oocyte (egg) donation.

Acupuncture may be helpful in the treatment of some cases of female infertility due to problems with ovarian function. In a preliminary trial, women who did not ovulate were treated with acupuncture 30 times over three months. Effectiveness was determined by a combination of measures indicating ovulation was returning to normal.

How can I help prevent infertility?

You may not be able to prevent infertility resulting from genetic problems or an illness. However, you can do the following to reduce the risk of infertility:

* Prevent sexually transmitted diseases by using latex or polyurethane condoms. Also, have just 1 sexual partner who is not sexually active with anyone else.

* Limit the amount of alcohol you drink to no more than 1 or 2 drinks a week.

* Avoid the use of street drugs (such as heroin) and overuse of prescription and nonprescription drugs.

* Do not smoke.

* Maintain good personal hygiene and health practices.

Infertility is a tough situation for women. Many of them conclude that they can’t conceive, but that is not true. At times it takes long to conceive and even if then one is not able to, and then these medical aids are there to help one out of these difficult situations.



Brent

Cindy Heller asked:


Infertility is often thought as related to female but the facts are otherwise as up to fifty percent of the causes are due to male. From the underlying statistics, it is essential for the male to get tested as much as it is for the female. It could put men in a very compromising and embarrassing situation but early testing can save the women a lot of unnecessary pain and provide the couples with ready and definite answers to their infertility.

Many solutions are available for men who are infertile and you just need to know where to seek help. For conception to take place, the male have to be able to fertilize the egg in the right manner. If this does not take place, the causes are numerous and varied, therefore seeking solutions and treatments are essential in order for the couples to conceive.

There are wide varieties of treatment choices that can be found in today context and whichever treatments are dependable on the kind of infertility problems that you are encountering. In order for the right kind of treatments to be applied, you and your physician have to understand the type of infertility problem you are facing.

The infertility cause has to be indentified and not some unknown causes. Once the cause is found, the physician will have to determine how defective the ***** is and then the age of the female partner. Upon determination, the course of male infertility treatment can begin.

Certain causes of infertility are because of problems with the ***** and the seminal fluid or what is known as the reproductive organs. Generally there are definite causes and the right male infertility treatments are applied. A very widespread cause of male infertility is Varicocele and it is the result of problem with the varicose veins that are located in the path of the spermatic journey.

The varicose veins will be bigger than usual and do not dilate like before and there are a few signs to look out for. One of the symptoms is bigger than usual dilated veins that are found in the *******. Another symptom is a big swell, protuberance or inflammation on the ******* area that is unproblematic.

Some do not show any signs but for those problems, get an examination and remove the blockages to let the blood to flow normally. Surgical procedure is also used to repair the problem veins. With that the rate of pregnancy can be up to forty percent and it can take place in nine month after undergoing the treatment.

Another common problem is low ***** count and it is known as oligiospermis. With that a test will be carried out to determine the right ***** count, in addition to seeking out abnormality in shape and movement of the *****. For those with low ***** count, wearing loose clothing, doing on diet, abstaining from smoking and stop taking hot bath and saunas will be helpful. Absence of ***** is known as azoospermia but most issues can be treated if the right infertility treatment is applied.

For that form of male infertility treatment, an infertility pill known as Clomiphene citrate is used to stimulate the production of ***** in male as well as assisting the female to ovulate. Such treatment will greatly improve the ***** count in six months but there is a need to re-examine once every three months.

Besides that, a few changes in your behavior can be effective, such as lesser *********** for low ***** count to make certain that the ***** is increase dramatically in the ensuing period.

One of the better treatments for male infertility is through artificial insemination where the ***** and eggs are taken out with the fertilization occurring outside the womb. It is usually for those with low ***** count as just one ***** is needed to be injected to the egg. The age of the female will also be a determining factor as women get older; the success rate is much lower. On the other hand a combination of infertility treatment can be effective.

Seek the help of the health care providers for your male infertility problem and with the right type of treatments and the proper diagnosis, conception can occur. With so many diverse treatment options available, the percentage of conceiving is greatly enhanced. If all else fail, there is always adoption and the joy you bought forth to the orphaned child can greatly compensate your inability to conceive.



Anna