The Evaluation of Unexplained Infertility

An infertility evaluation is usually initiated after one year of regular unprotected intercourse in women under age 35 and after six months of unprotected intercourse in women age 35 and older. However, the evaluation may be initiated sooner in women with irregular menstrual cycles or known risk factors for infertility, such as Endometriosis, Tubal Disease, Premature Ovarian Aging, Immunological Infertility, a history of pelvic inflammatory disease, or reproductive tract malformations.

The basic evaluation can be performed by an interested and experienced primary care physician or an obstetrician-gynecologist. The primary care physician generally should refer the patient to a specialist for treatment of infertility. Many gynecologists initiate treatment prior to referral to a reproductive endocrinologist. This decision depends upon the results of infertility tests and clinician experience.

Multiple tests have been proposed for evaluation of female infertility. Some of these tests are supported by good evidence, while others are not. This topic will provide an evidence-based approach to the evaluation of female infertility. The etiology and treatment of female infertility, as well as the etiology, evaluation, and treatment of male infertility

Over the past decade, significant advances have occurred in the diagnosis and treatment of reproductive disorders. In this review, we discuss the routine testing performed to diagnose unexplained infertility. We also discuss additional testing, such as assessment of ovarian reserve, and the potential role of laparoscopy in the complete workup of unexplained infertility. Finally, we outline the available therapeutic options and discuss the efficacy and the cost-effectiveness of the existing treatment modalities. The optimal treatment strategy needs to be based on individual patient characteristics such as age, treatment efficacy, side-effect profile, and cost considerations.

Both partners of an infertile couple should be evaluated for factors that could be impairing fertility. The infertility specialist then uses this information to counsel the couple about the possible etiologies of their infertility and to offer a treatment plan targeted to their specific needs. It is important to remember that the couple may have multiple factors contributing to their infertility; therefore, a complete initial diagnostic evaluation should be performed to detect the most common causes of infertility, if present. When applicable, evaluation of both partners is performed concurrently. The recognition, evaluation, and treatment of infertility are stressful for most couples. The clinician should not ignore the couple's emotional state, which may include depression, anger, anxiety, and marital discord. Information should be supportive and informative.

Significant advances have occurred in the diagnosis and, more importantly, in the treatment of reproductive disorders over the past decade. The overall incidence of infertility has remained stable; however, the success rates have markedly improved with the widespread use of assisted reproductive technologies. Treatment options and success vary with the cause of infertility. Approximately 15% to 30% of couples will be diagnosed with unexplained infertility after their diagnostic workup.

Infertility is customarily defined as the inability to conceive after 1 year of regular unprotected intercourse. The infertility evaluation is typically initiated after 1 year of trying to conceive, but in couples with advanced female age (> 35 years), most practitioners initiate diagnostic evaluation after an inability to conceive for 6 months. The Practice Committee of the American Society for Reproductive

History and physical examination and Diagnostic tests - Findings on history and physical examination and Diagnostic tests may suggest the cause of infertility and thus help focus the diagnostic evaluation.

Important History points:

·         Duration of infertility and results of previous evaluation and therapy.

·         Menstrual history (cycle length and characteristics), which helps in determining ovulatory status. For example, regular monthly cycles with molimina (breast tenderness, ovulatory pain, bloating) suggest the patient is ovulatory and characteristics such as severe dysmenorrhea suggest endometriosis.

·         Medical, surgical, and gynecological history (including sexually transmitted infections, pelvic inflammatory disease, and treatment of abnormal Pap smears) to look for conditions, procedures, or medications potentially associated with infertility. At a minimum, the review of systems should determine whether the patient has symptoms of thyroid disease, galactorrhea, hirsutism, pelvic or abdominal pain, dysmenorrhea, or dyspareunia. Young women who have undergone unilateral oophorectomy generally do not have reduced fertility since young women have many primordial follicles per ovary; however, prior unilateral oophorectomy may impact fertility in older women as they may develop diminished ovarian reserve sooner than women with two ovaries.

·         Obstetrical history to assess for events potentially associated with subsequent infertility or adverse outcome in a future pregnancy.

·         Sexual history, including sexual dysfunction and frequency of coitus. Infrequent or ineffective coitus can be an explanation for infertility.

·         Family history, including family members with infertility, birth defects, genetic mutations, or mental retardation. Women with fragile X premutation may develop premature ovarian failure, while males may have learning problems, developmental delay, or autistic features.

·         Personal and lifestyle history including age, occupation, exercise, stress, dieting/changes in weight, smoking, and alcohol use, all of which can affect fertility.

Physical Examination:

·         The physical examination should assess for signs of potential causes of infertility. The patient's body mass index (BMI) should be calculated and fat distribution noted, as extremes of BMI are associated with reduced fertility and abdominal obesity is associated with insulin resistance.

·         Incomplete development of secondary sexual characteristics is a sign of hypogonadotropic hypogonadism. A body habitus that is short and stocky, with a squarely shaped chest, suggests Turner syndrome.

·         Abnormalities of the thyroid gland, galactorrhea, or signs of androgen excess (hirsutism, acne, male pattern baldness, virilization) suggest the presence of an endocrinopathy (eg, hyper- or hypothyroidism, hyperprolactinemia, polycystic ovary syndrome, adrenal disorder).

·         Tenderness or masses in the adnexae or posterior cul-de-sac (pouch of Douglas) are consistent with chronic pelvic inflammatory disease or endometriosis. Palpable tender nodules in the posterior cul-de-sac, uterosacral ligaments, or rectovaginal septum are additional signs of endometriosis.

·         Vaginal/cervical structural abnormalities or discharge suggest the presence of a müllerian anomaly, infection, or cervical factor.

·         Uterine enlargement, irregularity or lacks of mobility are signs of a uterine anomaly, leiomyoma, endometriosis, or pelvic adhesive disease.

·         Pathogenesis, clinical features, and diagnosis of endometriosis

·         Clinical features and diagnosis of pelvic inflammatory disease

·         Clinical manifestations and diagnosis of congenital anomalies of the uterus

·         Clinical manifestations and diagnosis of hyperprolactinemia

·         Diagnosis of and screening for hypothyroidism in nonpregnant adults

·         Diagnosis of hyperthyroidism

·         Clinical manifestations of polycystic ovary syndrome in adults

·         Clinical manifestations and diagnosis of Turner syndrome (gonadal dysgenesis)

·         Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)

Diagnostic Tests:

In addition to the history and physical examination, the initial diagnostic evaluation consists of:

·         Semen analysis to detect male factor infertility.

·         Documentation of normal ovulatory function. Women with regular menses approximately every four weeks with moliminal symptoms are almost always ovulatory.

·         A test to rule out tubal occlusion. We usually perform a hysterosalpingogram (HSG), but laparoscopy with chromotubation may be more appropriate in women suspected of having endometriosis. Indigo carmine can be used for the chromotubation dye.

Risk factors noted from the couple's history may indicate the need for additional testing after the initial infertility evaluation. When the results of a standard infertility evaluation are normal, practitioners assign a diagnosis of unexplained infertility. Although estimates vary, the likelihood that all such test results for an infertile couple are normal that the couple has unexplained infertility is approximately 15% to 30%.

A thorough but time-efficient investigation of the infertile couple is required prior to a diagnosis of unexplained infertility. Couples should undergo a semen analysis, ovulation testing, assessment of ovarian reserve, and imaging to assess for tubal and uterine factors before a diagnosis of unexplained infertility is made. This workup can be completed within 1 menstrual cycle. In the couples with unexplained infertility, various treatment modalities are available, including expectant management with lifestyle changes, operative laparoscopy, COH (clomiphene citrate or gonadotropins) with IUI, and IVF (with or without ICSI). The optimal treatment strategy needs to be based on individual patient characteristics such as age, treatment efficacy, side-effect profile such as multiple pregnancy, and cost considerations.

·         Couples should undergo a semen analysis, ovulation testing, assessment of ovarian reserve, and imaging to assess for tubal and uterine factors before a diagnosis of unexplained infertility is made.

·         The principal treatments for unexplained infertility include expectant observation with timed intercourse and lifestyle changes, clomiphene citrate and intrauterine insemination (IUI), controlled ovarian hyper stimulation with IUI, and in vitro fertilization (IVF).

·         Although expectant management is associated with the lowest cost, it results in the lowest cycle fecundity rates. It may provide an option for a couple with unexplained infertility in whom the female partner is young and the problem of oocyte depletion is not an immediate concern.

·         The most expensive, but also most successful treatment of unexplained infertility consists of the spectrum of assisted reproductive technology including IVF, with or without intracytoplasmic sperm injection. IVF is the treatment of choice for unexplained infertility when the less costly, but also less successful treatment modalities have failed.

·         The optimal treatment strategy needs to be based on individual patient characteristics such as age, treatment efficacy, side-effect profile such as multiple pregnancy, and cost considerations.

Why no eggs collected during IVF eggs retrieval process?

The number of eggs retrieved at egg collection can be predicted by the monitoring ultrasound scans, but very occasionally no eggs are collected from the fluid filled sacs in the ovaries (follicles), despite a satisfactory ultrasound appearance. Omission, delay or incomplete injection of the treatment that should be administered 36 hours before egg collection is sometimes responsible. Rarely, despite the injection, no eggs are collected. This is a poor prognostic sign that indicates a problem with poor egg quality and may prompt a discussion about using an egg donor to achieve pregnancy. When having IVF, most patients will grow a few follicles and the doctor will successfully retrieve eggs from most of these follicles.  However, sometimes no eggs are retrieved at the egg collection.   There are essentially five possible reasons as to why this may happen.

1.    The follicle may have ruptured (ovulated) prior to the egg collection. This may happen if the trigger injection is mistimed (i.e. given earlier than instructed); or if the egg collection is delayed beyond 37 hours of trigger injection administration. If the trigger timing is not correct or the egg collection procedure takes place 37 hours or more after the trigger injection is administered, there is a high chance that the follicles present on the ovaries can rupture.  This can result in the eggs being lost in the follicular fluid that is released from the ovary at the time of ovulation.

2.    The doctor may experience technical problems during the egg collection procedure. This may happen when the patient is very obese; or if there are adhesions (scar tissue) in the pelvic region.  Both obesity and scar tissue make it more difficult for the vaginal ultrasound probe to access your ovaries.  This can be a major problem if difficulties arise and the egg collection is not done under general anesthesia.  In these situations, it may be technically impossible for the doctor to access the ovaries to drain the follicles in search of eggs.

3.    Generally speaking the number of eggs expected from follicles seen on ultrasound scan is approximately 80-90%. It is important to remember that there will never be more than one egg per follicle. Unfortunately, when there are lower numbers of follicles, there is a higher chance that the egg is not collected in the follicle fluid.

4.    Another reason for the failure to retrieve eggs from mature follicles is due to empty follicle syndrome.

5.    Finally, another possible reason for no eggs being collected during the egg collection procedure is a patient may have low ovarian response.  This is more commonly seen in older women having IVF.  Apart from performing an Anti Mullerian Hormone test (AMH), there is no other way of predicting this in advance.

One in every three women is infertile but the causes of infertility vary. One of the most common causes is poor egg quality decreasing the chances of your eggs developing into a baby. You can still get pregnant but poor egg quality can make things more difficult. Thanks to modern technology, more and more options are becoming available to women who want to conceive.

Your eggs must respond to hormones in order for ovulation to start. Before your eggs can produce an embryo, they must be fertilized and cell divisions must begin. Internal issues such as production and chromosomal problems can prevent you from producing healthy embryos.

The older you get the lower quality eggs your body will produce. When you are in your 20s, or early 30s, you will have more good quality eggs than poor quality eggs. As you grow older these changes and the bad eggs outweigh the good eggs. Although you still have eggs left in your late 30s and early 40s, the chances of conception are more difficult, and the risk of miscarriage is higher. Other causes of poor egg qualities are:

·         Smoking

·         Cancer

·         Genetic Conditions

·         Health

·         Ovarian Surgery

·         Caffeine

·         Alcohol

·         Weight

Tests can be done to determine the quality and quantity of your eggs. Follicle-Stimulating Hormone (FSH) tests are completed to detect your levels of FSH. If they are low, specialists can prescribe fertility drugs (like Clomid) to increase your eggs’ quality. The ovarian reserve test reveals your remaining egg supply. Although males produce more sperm, females cannot produce more eggs. You are born with a specific number of eggs that does not increase over the years.

Do not be under the misconception that if you have a lot of eggs you will become pregnant. That is not always the case. Remember that the quality of your eggs is just as important as the quantity.

Age plays an important factor in the quality and quantity of your eggs but it is not always the deciding factor. For instance, a woman who is 25 can have poor quality eggs and a woman who is 45 can have good quality eggs. This is rare, but it is not impossible.

Do not let your menstrual cycle determine the quality of your eggs. Even though your menstrual cycle comes each month on time that does not necessarily mean you have high-quality eggs. It is also a myth that your eggs are only lost during ovulation. In fact, more of your eggs will be lost due to degeneration than ovulation.

Even though you have poor quality eggs, you are still able to get pregnant. There are also options available to you and your partner in the event that you do not get pregnant. One option is In Vitro Fertilization (IVF). During this procedure, your eggs are fertilized outside of your body before they are planted into your uterus. Alternatively, if your eggs are of poor quality, you can choose a donor who has a better quality of eggs, which can increase your chances of pregnancy.

What exactly is the difference between fresh vs. frozen eggs?

Researchers found that those who received eggs that had been donated by another woman and then frozen were just as likely to have a baby as women given fresh donor eggs. A difference that could have been due just to chance, the findings add to evidence that egg-freezing can work; whether it's a woman's own eggs or a donor's eggs. This is more positive reinforcement that egg-freezing is here, While it has long been possible to freeze sperm or embryos for future use in fertility treatment, the technology for freezing a woman's eggs is relatively new. Freezing eggs is trickier. 

The eggs tend to form ice crystals that damage their structure. But through a modern quick-freeze process, it has become possible to keep eggs in storage and use them later. One goal is to allow women to freeze their own eggs. A woman might want to do that ahead of a cancer treatment that could harm her fertility. In other cases, a woman in her 30s who cannot have a baby right now because of her career or because she doesn't have a partner may want to freeze eggs to use in the future.

For those of us involved in the world of donor egg, fresh donor egg cycles vs. frozen egg cycles are the talk of the town. What to do? Which one gets better results? What exactly is the difference between fresh vs. frozen?

Let’s first be clear on the difference. A fresh donor egg cycle is when you are working with a live donor that you picked just for you. You get the entire yield of her cycle, good or bad. If they retrieve 26 eggs from the donor, all those eggs are yours to use now or in the future. If the cycle only yields 8 eggs, then you get only those 8 to work with.

A frozen egg cycle is different from a frozen embryo cycle or thaw cycle. A thaw cycle is when you freeze embryos from a fresh cycle and either uses those embryos (fertilized eggs) for another biological sibling in the future or to try again if the first cycle was unsuccessful. Your frozen embryos are thawed for another transfer, thus, a thaw cycle.

A frozen egg cycle is when you work with an egg bank and only get a lot of eggs, unfertilized eggs, not embryos, from the egg bank. You then fertilize these eggs. You only get a lot of 6(usually) no matter how many were retrieved from the donor. If there were 24 eggs retrieved, these eggs will be divided into 4 lots of 6 eggs each and each lot goes to a different recipient.

Whether one way to go is better or not is really a very individual decision. It depends on your circumstances and what your particular needs are. Do you want only one child? Are you going to try for siblings or biological siblings? Do you have insurance? Are you an international recipient? Is your time very limited? Are you trying to match with a particular ethnicity?

Most people think doing a frozen egg cycle from an egg bank works out to be cheaper, well it depends. A single transfer frozen egg cycle is cheaper, yes, but there are many things you must take into account before making this choice. If you choose the one cycle option, you will receive a lot of about 6 eggs, from the egg bank. Out of these 6 eggs, you hope at least 4 fertilize, it may be less. You will most likely transfer two. Hopefully it will work and you will get pregnant. It is unlikely that the remaining two will freeze for another cycle. It is possible but unlikely. If you do not get pregnant, you have nothing left and need to pay for another donor egg bank cycle.

Many say, well there is another guaranteed option. Yes, there is, but this is very expensive, more than a fresh cycle. If you do not get pregnant on the first try you can try and try again, up to 6 times. Something to consider, do you really want to go through this 6 times? Once you have done it once, you will see that this prospect is far from appealing. Secondly, if it does work the first or second try, you have now paid a fortune for a guaranteed option that you did not need to use. This does not mean you got pregnant on the first cycle and now you want a sibling and get to do it again, at no cost. You got pregnant. If you want a sibling, you pay for a complete new lot of eggs and it is very unlikely the same donor eggs will still be available for a biological sibling cycle.

If you do a fresh donor egg cycle, you pick your donor and this donor is only doing this cycle for you. All her eggs go to you. They are not shared with 4 other couples all over the country. If the cycle yields 26 eggs and even just 15 fertilize, you transfer 2 and have let’s say have 6 frozen, well, those are 6, healthy, good quality, fertilized embryos. You can try again and do a thaw cycle if it does not work the first time or save them for a biological sibling in the future at no extra cost to an agency or egg bank.

Some other things to consider when making this decision:

v  Egg banks have a very low number of donors. Their donors match very quickly. If you are looking for a particular donor, their selection is very limited. You must make a fast decision or the donor you liked may be gone.

v  You will not have the option of meeting the donor or negotiating with the donor in any way. You cannot ask more questions or get more photos.

v  You do not know how many other couples were or will be successful with this donor and there may be several live, half siblings.

v  Frozen egg cycles are much faster so if time is a concern, doing frozen eggs may be the best option for you.

v  Most frozen eggs are pre-screened so you are not taking the risks of working with a fresh donor, certainly if you are working with a repeat donor. No medical surprises. Although using a repeat fresh donor offers the same benefits.

v  With frozen eggs you do not have to sync your cycle with the donor’s therefore, the cycle is quick and easy. You do not have to stress and worry if the donor’s retrieval will go well. That part is already done.

It used to be that once you made a decision to do donor egg, the decision was made. Now, you have to decide on what type of donor eggs you will use.

The psychosomatic impacts and effects of infertility on infertile couples

It is a widely held expectation that if and when we choose to, we will be able to have a family. We do not challenge this assumption until difficulties in conceiving are encountered and for some this presents a major life crisis. The pain and loss can be immense. And, not surprisingly, infertility can have a significant negative impact on marital and sexual relationships. It is a multilayered and complex phenomenon and a number of issues are involved for the individual and couple going through it, as it spans the biological, emotional, physical, relational, social, financial and psychological domains.

The Impact and effects of infertility

This differs between males and females, regardless of the cause. It is the nature of these different experiences, in addition to the actual infertility issue, that can exert a significant strain on the couple relationship. The extent to which infertility exerts a negative psychological impact can differ between individuals and couples and is likely to be due to a number of factors, including: their desire for a child/family; past experience; family history; relationships past and present; diagnosis; cultural beliefs; and treatment outcome. These factors are also likely to contribute to whether infertility becomes an experience that prompts individuals and/or couples to seek counseling, at what stage and for how long.

The impact of infertility in females and males outlined below describes the key characteristics that are experienced by each member of the couple regardless of the cause of infertility; like male factor, female factor or unexplained. The experience is doubtless more complex than the descriptions suggest and each individual and couple will have their own unique experiences – not to mention diagnosis or lack of one – that feed into their responses to infertility, and which ideally need to be established and explored in the course of counseling.

Impact and effects on females

The female experience can be both complex and painful. It is generally characterized by periods of intense feelings of isolation – from her partner, her social circle and society. As more than one female client has reflected, it can feel as if they are ‘on the outside looking in on the rest of the world’. Females can feel unsupported and misunderstood throughout the experience, which adds to their despair and isolation. Pregnancy and motherhood is inextricably wrapped up in perceptions of femininity, and infertility can evoke a pervasive sense of failure as a woman, a person, and, in cases of unexplained and female factor infertility, she can feel that her body has failed her. 

All of which can have a devastating effect on self esteem. For those females who desire a child, this desire can increase as the possibility of having one reduces and for some it can become overwhelming, which creates a sense of urgency about finding a ‘solution’ to the problem. The result of this can be that treatment is pursued without pausing to consider the impact of this route on them, their body, their partner and their relationship. Treatment can be an unpredictable, long drawn-out rollercoaster of hoping, waiting and disappointment, which may or may not result in the birth of a child, and which can take a serious toll on females in a number of ways. Ultimately the experience for females can be one of grief.

Impact and effects on males

Whilst many males have a strong desire for a child and a family, unlike many females they tend to have a ‘pragmatic ambivalence’ towards fatherhood and children. That is, they will be happy if it happens; yet can come to accept if it does not. A symptom of their pragmatic ambivalence is that they consciously adopt a compliant position in relation to treatment. One consequence of this and their inability to ‘fix the problem’ – as perhaps they can in other situations – is that they tend not to express their negative feelings about the treatment process or how they feel about having/not having children, to their partner. This can be mistaken by their partner as ‘not caring’, but, on the contrary, it is often because they care about their partner so much that they adopt this position. This, in combination with the medical focus on the female, can leave males feeling marginalized and inadequate throughout the experience, and this is further compounded in cases of male-factor infertility. It can also lead to a build-up of resentment, which is mirrored by their partner.

The experience for males can be an anxiety-filled one that poses a major threat to their masculinity. However, it is not necessarily an experience they either want or feel able to share with their partner, or anyone else. And unfortunately, this can lead people around them to make the assumption that they are ‘OK’ and ‘coping fine’. This is often not the case and, moreover, it can add to their anxiety and sense of inadequacy. Another feature of the experience for males is that they worry about the pressure on their partner, and their partner’s increasing desire for a child, and the prospect of what might happen in the future if they do not achieve their goal. So it can be a time of great insecurity for males.

Impact and effects on the couple

A combination of factors, including female sense of isolation, male pragmatic ambivalence, growing resentments, the medical, emotional and financial pressures of treatment and uncertainty about what the future holds, can exert extreme stress on the couple relationship. This normally manifests in a distance between them. The result of this distance is at best a lack of communication and at worst a breakdown of communication, which for many couples can result in separation. Throughout the experience, couples tend to oscillate between periods of distance and closeness, and the nature and frequency of these distances is likely to be a key factor in whether couples stay together during and beyond the experience.

How can counseling helpful for infertile couples?

Given that infertility impacts on males and females in distinct ways and that they tend to deal with it in their own way, it follows that they each have distinct counseling needs. The couple unit also has its own distinct counseling needs. So there is a role for both individual and couple counseling, and, where there are older children involved, there is a case for family therapy.

How counseling helpful for females partner

The sense of extreme isolation in females can be a distressing time, during which they experience high levels of negative emotion and often feel unsupported and not understood. Here, counseling can be of great benefit, and a long-term counseling relationship may be of benefit throughout their journey, as and when they feel they need support. In addition, there are points which can be particularly difficult for females, where counseling can help. These include: the time around treatment eg immediately prior to, during and following, regardless of outcome; at critical points such as a miscarriage, anniversaries of due dates of lost pregnancies; when friends/family fall pregnant; and on being told treatment is not a viable option with their own eggs.

Following treatment, and regardless of whether they become mothers or not, females can experience a ‘delayed’ reaction in which they may be confronted with a host of issues that have been unresolved due to being on the ‘treatment treadmill’. Counseling can play an important role in terms of minimizing or preventing this reaction, which may also have a negative effect on the bonding process with a child or children.

How counseling helpful for males partner

As mentioned above, many males do not necessarily have a desire or need to discuss their feelings with anyone, let alone a ‘counselor’, and may run in the opposite direction if it is suggested, particularly in cases of male-factor infertility. However, this reaction is not as straightforward as it appears. Many males who do access counseling will reflect that if they had known ‘what counseling was’ they would probably have gone for it sooner, particularly in cases of male factor infertility. They also expressed their concerns about confidentiality – which their partner might ‘find out’ how they really felt. This can act as a deterrent. Yet many males say they do feel the need to talk, in private, to someone outside of their relationship about the trauma of the experience but that they did not necessarily know how to find a counselor or what to expect when they got there. 

Males who do access counseling, in addition to talking about their feelings, tend to want to gain some kind of understanding about infertility and its impact. This includes a desire to understand the medical diagnosis and procedures and what the female experiences emotionally and physically, so that they know how to help their partner. Males also have a desire for their partner to understand what they may be experiencing emotionally and psychologically so that they are not perceived as ‘not caring’ and ‘being fine’, when often they are not, despite outward appearances.

How counseling helpful for couples

Couples can benefit from counseling at each stage of the infertility journey, chiefly through the facilitation of communication and understanding between them. In addition, couples can use counseling to help them deal with a number of specific issues as they arise – such as decision-making around treatment options, miscarriages, failed cycles and when they achieve a pregnancy, for instance.

What are the limitations of counseling?

Given the distressing nature of infertility, it is not surprising that many individuals and couples express a desire to receive psychological support. Yet what is perhaps surprising is that less than 25 per cent tend to access it. There are the feelings of failure (females) and inadequacy (males) which contribute to the low uptake. But part of the explanation is that, unlike medical intervention, counseling cannot provide a ‘solution’ to the problem of infertility and so it is often not considered or offered.

Furthermore, counseling often tends to focus on realistic goals and objectives, which clients do not always find useful, and some can find this counterproductive. At the time of treatment, couples feel a need to be optimistic and strong to cope with the rigorous demands of it. They are also likely to be full of hope for the outcome of the treatment cycle and their future. They may not wish to discuss the more bleak and painful options at this stage. Counselors working with this client group need to be aware of this and be able to work with clients in a way they find beneficial.

Some queries and their replies regarding IVF

Query: Will the IVF technique damage my ovaries?

REPLY:  There is no evidence to suggest that either normal laparoscopy or ultrasound egg retrieval damages the ovaries. In fact, some reports in the medical literature suggest that following ovarian biopsy, pregnancies occur in couples with a long-term history of infertility.

QUERY: Will scar tissue around my ovaries make it impossible to retrieve the eggs?

REPLY:  Not ordinarily. The surgeon must be able to see the follicles in order to guide the needle to the proper spot for retrieval of the eggs whether by sonographic (ultrasound) or surgical methods.

QUERY: What if I ovulate before oocyte (also called egg or ovum) retrieval?

REPLY:  Once ovulation has occurred it is impossible to retrieve the eggs. The entire team of physician, nurse and embryologist will monitor your cycle very carefully to avoid premature ovulation.

QUERY: If an egg is not retrieved or if the technique does not produce a pregnancy on the first attempt, how soon can the procedure are repeated?

REPLY:  This depends on the individual. The primary reason for delay is to allow the patient's normal menstrual cycle to resume, which may take 2 to 3 cycles.

QUERY: How many times will IVF be repeated per couple?

REPLY:  There is no specific number. This is determined by the couple together with the physician.

QUERY: Can we have intercourse during the two-week period before an IVF procedure is performed?

REPLY:  Most definitely. We recommend that the husband refrain from ejaculation for at least 48 hours, but for no more than 5 to 6 days preceding egg retrieval. This precaution assures that the semen sample obtained for IVF will contain a maximum number of healthy, motile sperm.

QUERY: After the IVF procedure, how long must we wait to have intercourse?

REPLY:  Although a definite time of abstinence to avoid damage to the pre-embryo has not been determined, most experts recommend abstinence for two to three weeks. Theoretically, the uterine contractions associated with orgasm could interfere with the early stages of implantation. However, intercourse the night before pre-embryo transfer is acceptable. Some physicians will advise intercourse before transfer as they feel that this will improve the chances of a pregnancy.

QUERY: What about other activities? How soon can I resume my normal routine?

REPLY:  The IVF team recommends that the patient be sedentary for a full 24 hours following pre-embryo placement in the uterus. Strenuous exercises such as jogging, horseback riding, swimming, etc. should be avoided until pregnancy is confirmed. Otherwise, the patient is free to return to her regular activities.

QUERY: How soon will I know if I'm pregnant?

REPLY:  Pregnancy can be confirmed using blood tests about 13 days after egg aspiration. Pregnancy can be confirmed by ultrasound 30 to 40 days after aspiration.

QUERY: I had my tubes tied (tubal ligation) several years ago. Would I be a candidate for IVF?

REPLY:  Perhaps, in certain situations, IVF may be cheaper and physically less demanding than surgery to repair you fallopian tubes.

QUERY: What drugs are given to stimulate the ovarian follicles and to maintain the lining of the uterus prior to implantation of the pre-embryo?

REPLY:  Four to five medications normally are given:

1. Leuprolide acetate (Lupron), an injectable drug that blocks secretions of the pituitary gland, thereby optimizing the number of oocytes retrieved;

2. Human menopausal gonadotropin (Pergonal or hMG) or Follicle Stimulating Hormone (Metrodin or FSH), hormones that stimulate ovarian activity, are injected daily for about 6-10 days prior to the procedure;

3. Human chorionic gonadotropin (hCG), a hormone that mimics the action of the hormone which naturally induces ovulation, is injected 34 to 36 hours before retrieval and may be used after retrieval to supplement natural progesterone production;

4. Progesterone, a natural hormone that enables the uterus to support pregnancy, may be used as a daily injection after egg retrieval; and

QUERY: What side effects, if any, can these drugs cause?

REPLY: No pronounced side effects have been associated with any of these drugs. However, the patient should inform the physician of ANY allergies she has or of any previous adverse reactions to drugs.

QUERY: Will I have an egg in every follicle?

REPLY:  It varies from patient to patient . As many as half of the follicles may not contain an egg in some patients.

QUERY: Is there a possibility of multiple births with IVF?

REPLY: Yes, when multiple pre-embryos are transferred. 25%. of pregnancies with IVF are twins. (In normal population, the rate is one set of twins per 80 births.) Triplets are seen in approximately 2-3% of pregnancies.

QUERY: Is there an increased chance of birth defects if I become pregnant through IVF?

REPLY:  There are no known ill effects. Abnormal pre-embryos, even those produced through normal fertilization, do not seem to mature. However, any long-term effects of IVF remain to be determined.

QUERY: How much time does the entire procedure require?

REPLY:  Approximately three weeks (all as an outpatient). Fertility drugs are administered to stimulate the ovaries. Then during the four to six days prior to ovulation, the patient is monitored by ultrasound as well as by hormone levels.

QUERY: What happens to any extra pre-embryos?

REPLY: A maximum of four pre-embryos will be transferred to the uterus for possible implantation. Patients will have several other options regarding the disposition of the remaining pre-embryos. One option is to freeze pre-embryos for your later use. Other options are to donate or simply dispose of them. Excess pre-embryos, if any, belong to you, and you will determine what is to be done.

Interpretation of Empty follicle syndrome

Empty follicle syndrome (EFS) has been defined as a condition in which no oocytes are retrieved from mature ovarian follicles with apparently normal follicular development and estradiol levels, after Controlled ovarian hyper stimulation (COH) for an assisted reproductive technology (ART) cycle, despite repeated aspiration and flushing. No oocytes are retrieved even after many ultrasounds; estradiol levels which show many potential follicles, Empty follicle syndrome are a frustrating situation at times.

It is not uncommon to hear women report that their IVF-egg retrieval yielded far fewer eggs than was expected and that when asking for an explanation they were told by their doctor that many of their follicles were “empty” and contained no eggs. This is at best an oversimplification of a complex situation, or at worst a flagrant misstatement; all follicles by definition must contain eggs.

True, it is not unusual or irregular for egg retrieval to yield a few less eggs than the number of follicles would suggest. However, when less than 50% of follicles >15mm fail to yield eggs, something is wrong. So how and why does it happen?

·         First, The LH surge that precedes spontaneous ovulation and also with the hCG trigger shot given to induce ovulation following the use of fertility drugs, the egg undergoes “ripening” to prepare for fertilization. This involves (among other events) a rapid halving in the number of its chromosomes (meiosis). At the same time, enzymes are released that loosen the cells (cumulus oophorus) that surround and bind the egg to the inner wall of the follicle. This is necessary to enable the egg to come free at ovulation and/or at the time of egg retrieval.

·         The problem is that with poorly developed eggs, the latter mechanism often fails, leaving such eggs tightly “stuck” to the follicle wall and unable to come free, often in spite of vigorous attempts to flush them loose. That is why the more difficult it is to successfully aspirate an egg at egg retrieval, the more likely it is that such an egg is chromosomally abnormal and “incompetent” i.e. incapable of developing into a normal pregnancy. This state of affairs is most commonly encountered in women with diminished ovarian reserve i.e. “poor responders”, women over 40 and in women with polycystic ovarian syndrome who do not receive an optimal protocol of controlled ovarian hyper stimulation.

So the term “Empty Follicle Syndrome” is a misnomer! Yet the circumstances surrounding failure of numerous follicles to yield the eggs they contain at the time of egg retrieval only serves to underscore the need to individualize COH protocols and to time the administration of the “hCG trigger”, precisely.

Risk Factors of Empty follicle syndrome:

·         The risk factor for Empty follicle syndrome increases with age.

·         About 24% of patients between the age of 35 to 39 years of age; 57% for those; 40 years of age.

·         It has also 20% chances of recurrence; the risk of recurrence increases with advancing age of the patient.

Causes of Empty follicle syndrome:

·         Inappropriate timing of hCG

·         PCOS

·         Dysfunctional folliculogenesis, in which oocyte atresia occurs with normal hormonal response

·         Genetic factors

·         Advanced ovarian ageing through altered folliculogenesis

Types of empty follicle syndrome:

Empty follicle syndrome can be classified into 2 types

·         Genuine Empty follicle syndrome (GEFS)

·         False Empty follicle syndrome (FEFS)

1.   Genuine Empty follicle syndrome (GEFS):

Genuine Empty follicle syndrome is defined as failure to retrieve oocytes from mature follicles apparently after Controlled Ovarian stimulation for IVF.

It may be due to dysfunctional folliculogenesis, the oocytes fail to retrieve even with normal follicular development; steroidogenesis in presence of optimal beta human choriogonadotrophin (bhCG) levels on the oocyte retrieval

2.  False Empty follicle syndrome (FEFS):

False Empty follicle syndrome (FEFS) is defined as failure to retrieve oocytes in presence of low beta human choriogonadotrophin hormone (bhCH) level on the day of oocyte retrieval

It is basically due to human errors or pharmaceutical reasons

The egg undergoes “ripening” to prepare for fertilization by LH surge which precedes spontaneous ovulation also hCG; various fertility drugs are given to induce ovulation. Enzymes are released at the same time that loosens the cells (cumulus oophorus) that surround and bind the egg to the inner wall of the follicle. This is necessary to enable the egg to come free at ovulation and/or at the time of egg retrieval. The problem is that with poorly developed eggs, the latter mechanism often fails, leaving such eggs tightly “stuck” to the follicle wall and unable to come free, often in spite of vigorous attempts to flush them loose.

That is why the more difficult it is to successfully aspirate an egg at egg retrieval, the more likely it is that such an egg is chromosomally abnormal and incapable of developing into a normal pregnancy. EFS do not represent a permanent patho-physiological condition and most cases occur only sporadically. The ovarian follicles of patients with so-called EFS may not actually be devoid of viable oocytes. The problem seems to be that of inadequate pre-ovulatory follicular changes arising from either poor bioavailability of LH or hCG or too short an interval between the onset of these changes and follicular aspiration.

EFS do not predict a reduced fertility potential in future cycles. Nevertheless, whatever the cause of EFS, such patients should be counseled regarding its possibility of recurrence and future poor prognosis.

The empty follicle syndrome (EFS) is a frustrating condition in which no oocytes are retrieved in an IVF cycle. Although this is an infrequent event in IVF patients, the economic consequences as well as the emotional frustration of a cancelled cycle due to the inability to obtain oocytes are enormous. The mechanisms responsible for EFS remain obscure, though many hypotheses have been put forward ranging from dysfunctional folliculogenesis to a drug-related problem. We found that the EFS is a rare event (1.8% of oocyte retrievals) but with profound implications for counseling the couple about their future reproductive performance. The chances of recurrence of EFS increase with the age of the patient (24% recurrence rate for the 35–39 year age group, and 57% for those over 40 years). We postulate that ovarian ageing, through altered folliculogenesis, may be implicated in the etiology of EFS and its recurrence.

Internet connected through Wi-Fi decreases male sperm motility

In recent years, the use of portable computers (laptops, connected to local area networks wirelessly, also known as Wi-Fi) has increased dramatically. Laptops have become indispensable devices in our daily life, offering flexibility and mobility to users. People using Wi-Fi may be exposed to radio signals absorbing some of the transmitted energy in their bodies. Portable computers are commonly used on the lap, therefore exposing the genital area to radio frequency electromagnetic waves as well as high temperatures. Infertility is a common worldwide condition that affects more than 70 million couples of reproductive age. It has been suggested that male fertility has declined during the past several decades. Such decline has been attributed to the direct or indirect exposure to certain environmental factors such as electromagnetic waves.

Extremely low frequency magnetic fields can initiate a number of biochemical and physiological alterations in biological systems of different species. Many of these effects have been associated with free-radical production. Free radicals are causative factors of oxidative damage of cellular structures and molecules such as lipids, proteins, and nucleic acids. Free radicals react with polyunsaturated fatty acids in cell membranes promoting a process called lipid peroxidation. In human spermatozoa the presence of unesterified polyunsaturated fatty acids is causally associated with the induction of reactive oxygen species (ROS) generation and lipid peroxidation. Damage may occur at the membrane level, leading to immotility and cell death, or at the DNA level. DNA integrity is essential to normal conception.

Sperm DNA fragmentation has been associated with impaired fertilization, poor embryonic development, high rates of miscarriage, and increased incidence of morbidity in the offspring, including childhood cancer. It has been proposed that genetic and environmental factors would be involved in the etiology of sperm DNA damage. The electromagnetic waves from mobile phones may cause DNA damage, in addition to decreased motility and viability. Increased levels of intracellular ROS would be the cause of these deleterious effects. Portable computers using Wi-Fi emit RF-EMW and are typically positioned close the male reproductive organs. Their potential negative effects on male germ cells have not been elucidated. To assess this potential association we used an in vitro model incubating human sperm in the presence of an active portable computer connected to the internet by Wi-Fi.

The use of laptop and PC computers wirelessly connected to local area networks (Wi-Fi) has increased dramatically in recent years. People using Wi-Fi may be exposed to radio signals. The use of portable computers (connected via Wi-Fi) on the lap exposes the genital area to radio frequency electromagnetic waves (RF-EMW) and high temperatures.

It has been postulated that declines seen in male fertility over recent years may be related to various environmental factors, including RF-EMW. The effects of extremely low frequency magnetic fields may be associated with oxidative damage of cellular structures and molecules. Oxidative damage to spermatozoa could affect motility or damage DNA. Deleterious effects on spermatozoa from mobile phone use have been reported.

Since the dawn of wireless technology, it's been a fear amongst the panic-prone that the technology emits radiation that causes brain tumors, mutant babies and plane crashes. Couple that with man's unorthodox paranoia that everything from underwear to Mountain Dew; can lower sperm count and we've heard our fair share of "wireless technology will destroy sperm" myths.

But according to a new study, this myth might have a basis in truth. They took sperm samples from 29 healthy men. They separated each sample into two containers. Motile sperm were selected by ‘swim up’. Each sperm suspension was divided into two aliquots. One sperm aliquot (experimental) from each patient was exposed to an internet-connected laptop by Wi-Fi for 4 hours, whereas the second aliquot (unexposed) was used as control, incubated under identical conditions (including the same temperature) without being exposed to the laptop. What they found was enough to make some men reconsider perching their laptops on their crotch.

Their findings stated that 25 percent of the sperm in the samples placed under the laptop stopped swimming as opposed to 14 percent from the control group. They also found that nine percent of the Wi-Fi exposed sperm showed DNA damage as opposed to three percent from the control.

While the experiment didn't conclusively prove that Wi-Fi is dangerous to sperm, there was enough of an effect that scientists recommended further testing. Our data suggest that the use of a laptop computer wirelessly connected to the internet and positioned near the male reproductive organs may decrease human sperm quality.

But before you invest in a lead codpiece, Ejaculated sperm are particularly sensitive to many factors because outside the body they don't have the protection of the other cells, tissues and fluids of the body in which they are stored before ejaculation. Therefore, we cannot infer from this study that because a man might use a laptop with Wi-Fi on his lap for more than four hours then his sperm will necessarily be damaged and he will be less fertile.

Some very Important Points to be note:

·         The data suggest that the use of a laptop computer connected wirelessly to the internet and positioned near the testes may decrease sperm quality.

·         The potential effects of the heat produced by the laptop were controlled for in this study, as other studies have shown increased scrotal temperatures from laptop use.

·         As this was an ex vivo study, the effects of laptop use on sperm in the body can only be speculative.

·         The effects seen were due to RF-EMW but they were not able to discount the possibility that it was the radiation from the laptop itself causing the effect.

·         Further in vitro and in vivo investigations are required to confirm these findings and the postulated mechanism.

·         Uses of laptop and computers which connected to internet through Wi-Fi decreases human sperm motility and increases sperm DNA fragmentation? It is very interesting to raise few curiosity and questions regarding this interesting matter.

Doctors and Scientists around the world have warned against unnecessary exposure of children to wireless technology and recommend safer wired internet connection instead, both in school and at home. We are parents who fully support the use of computers and the incorporation of technology in education, and we believe that it must be implemented in a safe manner.

How to get pregnant when Absence of Periods or Irregular Periods

The medical term used to describe "absence of periods" is amenorrhea. Women normally do not menstruate before puberty, during pregnancy, and after menopause. If a woman does not get her period when she normally should, it may be the symptom of a treatable medical condition.

There are two types of amenorrhea: primary amenorrhea and secondary amenorrhea. Primary amenorrhea is when a young woman has not had her first period by the age of 16. Secondary amenorrhea is when a woman who has had normal menstrual cycles stops getting her monthly period for three or more months. Amenorrhea can be caused by any number of changes in the organs, glands, and hormones involved in menstruation.

Possible causes of primary amenorrhea (when a woman never gets her first period) include:

·         Failure of the ovaries (female sex organs that hold eggs)

·         Problems in the central nervous system (brain and spinal cord) or the pituitary gland (a gland in the brain that makes hormones involved in menstruation)

·         Poorly formed reproductive organs

In many cases, the cause of primary amenorrhea is not known. Common causes of secondary amenorrhea (when a woman who has had normal periods stops getting them) include:

·         Pregnancy

·         Breast feeding

·         Stopping the use of birth control

·         Menopause

·         Some birth control methods, such as Depo-Provera

Other causes of secondary amenorrhea include:

·         Stress

·         Poor nutrition

·         Depression

·         Certain drugs

·         Extreme weight loss

·         Over-exercising

·         Ongoing illness

·         Sudden weight gain or being very overweight (obesity)

·         Hormonal imbalance due to polycystic ovarian syndrome (PCOS)

·         Thyroid gland disorders

·         Tumors on the ovaries or brain (rare)

·         A woman who has had her uterus or ovaries removed will also stop menstruating.

What are causes may increase your risk for problems from missed or irregular periods?

Many conditions, lifestyle choices, medications, and diseases interfere with your ability to heal or fight infection. You may be at risk for a more serious problem from your symptoms if you have any of the following. Be sure to tell your health professional.

Conditions

·         Eating disorders, such as anorexia or bulimia

·         Ectopic pregnancy or miscarriage

·         Menopause

·         Pregnancy

·         Recent gynecologic treatments or procedures:

·         Abortion

·         Dilation and curettage

Lifestyle choices

·         Alcohol abuse or withdrawal

·         Drug abuse or withdrawal

·         Endurance athletics

·         Smoking or other tobacco use

·         Unprotected sex

Medications

·         Corticosteroids, such as prednisone

·         Medications to prevent organ transplant rejection

·         Medications to treat cancer (chemotherapy)

·         Radiation therapy

Diseases

·         Cancer

·         Diabetes

·         Diseases that can affect hormone balance, such as:

·         Adrenal disease

·         Ovarian cysts

·         Pituitary disease

·         Polycystic ovary syndrome

·         Thyroid disease

·         Human immunodeficiency virus (HIV) infection

Irregular Periods and Getting Pregnant

Irregular or abnormal ovulation accounts for 30% to 40% of all cases of infertility. Having irregular periods, no periods, or abnormal bleeding often indicates that you aren't ovulating, a condition known clinically as anovulation. Although anovulation can usually be treated with fertility drugs, it is important to be evaluated for other conditions that could interfere with ovulation, such as thyroid conditions or abnormalities of the adrenal or pituitary glands.

Getting Pregnant With Ovulation Problems

Once your doctor has ruled out other medical conditions, he or she may prescribe fertility drugs to stimulate your ovulation. The drug contained in both Clomid and Serophene (clomiphene) is often a first choice because it's effective and has been prescribed to women for decades. Unlike many infertility drugs, it also has the advantage of being taken orally instead of by injection. It is used to induce ovulation and to correct irregular ovulation by increasing egg production by the ovaries.

Clomiphene induces ovulation in most women with anovulation. Up to 10% of women who use clomiphene for infertility will have a multiple gestation pregnancy usually twins. (In comparison, just 1% of the general population of women delivers twins.)

The typical starting dosage of clomphene is 50 milligrams per day for five days, beginning on the third, fourth, or fifth day after your period begins. You can expect to start ovulating about seven days after you've taken the last dose of clomiphene. If you don't ovulate right away, the dose can be increased by 50 milligrams per day each month up to 150 mg. After you've begun to ovulate, most doctors suggest taking Clomid for no longer than six months. If you haven't gotten pregnant by then, you would try a different medication or get a referral to an infertility specialist.

These fertility drugs sometimes make the cervical mucus "hostile" to sperm, keeping sperm from swimming into the uterus. This can be overcome by using artificial or intrauterine insemination (IUI) injecting specially prepared sperm directly into the uterus to fertilize the egg.

Depending on your situation, your doctor may also suggest other fertility drugs such as Gonal-F or other injectable hormones that stimulate follicles and stimulate egg development in the ovaries. These are the so-called "super-ovulation" drugs. Most of these drugs are administered by injection just under the skin. Some of these hormones may over stimulate the ovaries (causing abdominal bloating and discomfort); thus, your doctor will monitor you with frequent vaginal ultrasounds and blood tests to monitor estrogen levels. About 90% of women ovulate with these drugs and between 20% and 60% become pregnant.

Polycystic Ovary Syndrome (PCOS)

A common ovulation problem that affects about 5% to 10% of women in their reproductive years is polycystic ovary syndrome (PCOS). PCOS is a hormonal imbalance that can cause the ovaries not to work. In most cases, the ovaries become enlarged and appear covered with tiny, fluid-filled cysts. Symptoms include:

·         No periods, irregular periods, or irregular bleeding

·         No ovulation or irregular ovulation

·         Obesity or weight gain (although thin women may have PCOS)

·         Insulin resistance (an indicator of pre-diabetes)

·         High blood pressure

·         Abnormal cholesterol with high triglycerides

·         Excess hair growth on the body and face (hirsutism)

·         Acne or oily skin

·         Thinning hair or male-pattern baldness

Getting Pregnant When You Have PCOS

If you have PCOS and you're overweight, losing weight is one way to improve your chances of pregnancy. Your doctor also might prescribe medication to lower your insulin levels, since elevated insulin levels caused by your body's inability to recognize insulin has been found to be a common problem among many women with PCOS. Chronically elevated insulin levels can also lead to diabetes. Women with PCOS may be at higher risk for developing heart disease, 2 types of diabetes, and endometrial cancer, especially if PCOS is untreated.

PCOS can't be cured, but there are treatments available to treat the symptoms of PCOS and the infertility associated with this condition. By stimulating ovulation, especially in women trying to conceive, and treating insulin resistance, regular ovulation and periods often are restored. A procedure known as in vitro fertilization, or IVF, is another potential treatment for women with PCOS.

Stress and Fertility

For couples struggling with infertility, it's a particularly cruel fact: Not only can infertility cause a lot of stress, but stress can affect fertility. It's known to contribute to problems with ovulation. For many people, the longer you go without conceiving, the more stress you feel. Fears about infertility may also lead to tension with your partner, and that can reduce your chances of pregnancy even further. After all, it's hard to have sex if one of you sleeps on the couch.

While it's a fact that coping with infertility is stressful, that doesn't mean you have to give into it. If your doctor can't find a medical cause for your ovulation problems, consider finding support groups or a therapist who can help you learn better ways to cope with the anxieties that come with infertility.

Some tips for reducing stress:

·         Keep the lines of communication open with your partner.

·         Get emotional support. A couples' counselor, support groups, or books can help you cope.

·         Try out some stress-reduction techniques such as meditation or yoga.

·         Cut down on caffeine and other stimulants.

·         Exercise regularly to release your physical and emotional tension.

·         Agree on a medical treatment plan, including financial limits, with your partner.