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

Bertil Hjert asked:


Nothing is more beautiful and satisfying then giving birth to a new life. A woman considers this as the best moment of her life. However, unfortunately, every woman cannot fulfill her dreams to give birth to the bundle of joy. Some suffer from infertility problems.

Medical science refers infertility to the lack of capacity of a person; male or female to conceive or let conceive a child via the process of sexual ***********.

When it comes to women, this condition is very severe and usually occurs in almost one out of six women. According to a research conducted, it is clear that female infertility is responsible for only about 40% of all cases of infertility. The most common causes of female fertility are endometriosis, blocked fallopian tubes and ovulation problems.

Fortunately, there are several infertility treatment options available these days. One of the most common among these options includes solutions from non-drug treatments.

Acupuncture can work wonders to treat infertility problems. However, most people have under estimated the power of this miraculous treatment option available for infertility.

Acupuncture can be effectively used in cases of infertility treatment where the actual cause of the problem is functional and not structural. Functional infertility can be referred to as a condition where the main problem lies with hormones or emotions of a person. Structural infertility on the other hand, is a condition of a blocked fallopian tube.

The main job of an acupuncturist is to observe the causes of infertility and then act accordingly.

Several studies have proved that acupuncture as an infertility treatment is extremely effective when used in combination with several infertility procedures including ‘in vitro’ fertilization.

When the acupuncture needles are inserted inside the female body there is a stimulation of some specific vital gender oriented chemicals existing in the body. This also accompanies with a feeling of good mental health as well as confidence that works towards making acupuncture more helpful.

Usually, the acupuncturist analyzes the reasons behind the increase in the success rate when the restoration of the flow of blood towards the reproductive organs proceeds. This finally results in the hormonal level normalization inside the body.

This facilitates ovulation and enhances the overall chances of conception. The best part is that there are no risks involved in going for acupunctures as a treatment for infertility.

Acupunctures treatments can also be carried out in combination with a wide variety of herbal medication specially prescribed for treating infertility. This increases the chances of treating the disease more effectively and successfully.

You can even go for a healthy diet and lifestyle change options in conjunction with acupuncture in order to treat infertility problems successfully. This increases the chances of achieving better results.

Acupuncture is also known to reduce the chances of miscarriages and trouble in pregnancies.

Remember that acupuncture is only effective in cases where the treatment is carried out by an experienced acupuncturist.

Make a thorough research prior to deciding on going for acupuncture as a treatment for infertility.



Georgia

Darrell Miller asked:


Infertility is typically defined as a failure to conceive after a year or more of regular intimate activity during the time of ovulation. This term can also refer to the inability to carry a pregnancy to term. About 6.1 million American couples are impaired when it comes to their ability to have children, with 2.1 million of these couples being infertile. The exact cause of the problem can be extremely difficult to pinpoint, as ovulation, fertilization, and the passage to the fertilized ovum through the fallopian tube and to the uterus are extremely complex processes. In order for pregnancy to occur, many events must work together perfectly.

In 40 percent of infertile couples, problems that affect the male partner are either partially or wholly the cause of infertility. Infertility in men is usually the result of a low ***** count or an anatomical abnormality. There are a variety of factors that can result in a low ***** count. Among these factors are alcohol consumption, endocrine disorders, exposure to toxins, radiation or excessive heat, recent acute illness or prolonged fever, testicular injury, and rarely, mumps-induced wasting of the *********. An abnormal enlargement of veins that drain the testicles, referred to as varicoceles, can cause infertility in men. This is because the veins of the testes are no longer able to moderate the temperature of the ********* correctly, which can negatively affect *****.

The most common causes of infertility in women include an ovulatory failure or defect, blocked fallopian tubes, endometriosis, and uterine fibroids. Additionally, some women are able to develop antibodies to their partners’ sperm, which causes the woman to almost be allergic to them. Chlamydia, a transmitted disease which affects 4 million Americans each year, also causes many cases of infertility. There are also psychological issues, such as stress or fear of parenthood, which can also contribute to infertility.

However, in most cases, stress is usually the result of infertility, not the cause of it. ***** abnormalities account for about 41 percent of infertility cases. The following reasons are the most common to explain why couples cannot conceive: the woman has endometriosis; the man has abnormal sperm, a low ***** count, or erectile dysfunction; the woman’s fallopian tubes are blocked; ovulation takes place rarely or irregularly; the couple is unable to have complete intimate relations; the cervical mucous attacks and kills the sperm; the woman does not manufacture enough progesterone to carry a baby to term; the woman is over thirty-four; and/or one or both members of the couple eats a poor diet and experiences too much stress.

The following nutrients are extremely beneficial in helping one or both partners deal with infertility: selenium, vitamin C with bioflavonoids, vitamin E, zinc, DMG, octacosanol, phosphatidyl choline, essential fatty acids, l-arginine, manganese, proteolytic enzymes, pycnogenol, raw orchic glandular, raw ovarian glandular, 7-keto DHEA, vitamin A, and vitamin B complex. Also, the following herbs have been shown to be beneficial in dealing with infertility: astragalus, damiana, ginseng, sarsaparilla, saw palmetto, yohimbe, dong quai, false unicorn root, gotu kola, licorice root, wild yam root, green oat, and yin-yang-huo. It should also be noted that heavy use of Echinacea, ginkgo biloba, and St. John’s wort may cause infertility in men, and should be avoided.

Infertility can be a complicated and mentally depressing due to lack of pregnancy by both men and women. Depression can lead to more stress and needs managed by a health care provider. Always consult your doctor when you think you are infertile. Natural vitamins like the ones listed above are available at your local or internet health food store. Look for name brands vitamins to ensure you receive quality supplements.

*Statements contained herein have not been evaluated by the Food and Drug Administration. Vitamins and herbs are not intended to diagnose, treat and cure or prevent disease. Always consult with your professional health care provider before changing any medication or adding Vitamins to medications.



Alex

Dr. Eric Daiter asked:


Infertility is defined by most as the inability to become pregnant or sustain pregnancy after one year of regular sexual activity without the use of contraceptives. Pregnancy can only occur when a chain of events happens uninterrupted. First, the woman must ovulate. The egg must be able to travel down the fallopian tube and be fertilized by a viable *****. Then the fertilized egg must be implanted into the uterus. The uterus must be able to support the pregnancy. If any of these systems are interrupted, then infertility may occur.

Male infertility can be caused by problems with producing sperm, ***** count or ***** mobility. Sometimes the ***** produced can be misshapen or distorted in a way that prevents it from moving correctly. This prevents it from reaching the egg. Sometimes men are born with this problem. Other times there are other factors causing the ***** count or mobility to be low. Illness, injury and disease can cause problems with the ***** that result in male infertility.

A man’s lifestyle can affect his infertility as well. Alcohol, drugs, poor diet, smoking, medications, extreme inactivity or too much exercise can all affect a man’s fertility. Age may be a significant factor. The older a man gets, the more likely he is to experience fertility problems. A fertility specialist may be able to help you diagnose what is causing your infertility, although sometimes a cause can not be determined.

Female infertility is often caused by problems with ovulation. Ovulation is when an egg is released from the ovary. Problems with ovulation can usually be detected by monitoring the menstrual cycle of the woman. If the cycle is irregular or has ceased, then there may be an ovulation problem.

If there is an egg to be fertilized, then it must be able to travel down the fallopian tube. If there is a blockage, then implantation in the uterus can not occur. If a fertilized egg gets stuck in the fallopian tube, then it can cause an ectopic pregnancy. Endometriosis, pelvic inflammatory disease and uterine fibroids can be other causes of infertility in women. Sometimes the uterus itself can be structurally misshapen or too distorted to support a pregnancy.

Many lifestyle factors should be considered when determining the cause of a female’s infertility. Age, illness, hormonal changes or imbalances, smoking, weight, alcohol use, smoking, exercise level and diet should all be evaluated. Sexually transmitted diseases can also cause infertility. Weight is a common cause of infertility. If a woman weighs too little or too much, it can affect the signal from the brain that tells the ovary to release the egg.

There are many causes of infertility for men and women that are not discussed here. You should talk with your doctor or infertility specialist about what specific causes of infertility you might be experiencing. Careful planning, lifestyle changes, hormonal treatments or surgery could help you conceive. The best thing to do is to come up with an infertility treatment plan that is right for you.



Todd