Female Infertility Treatment Options: Western And Traditional Chinese

ABSTRACT

This paper explores and contrasts the western medical (WM) and the traditional Chinese medical (TCM) approaches to fertility management. Although the likelihood of success using the WM approach has been well researched and TCM has not, it appears that, based on the best available evidence, the TCM approach may be just as effective as well as more economical. Moreover, the combination of WM and TCM may provide the best outcome for some couples. Treatment protocols using prepared Chinese herbal medicines are provided in Appendix 1. Additional information on IVF is provided in Appendix 2.

INTRODUCTION

As more couples in western countries delay having a family until the woman is in her early to mid-30’s, there is an increasing demand for assistance with conception, due to the age related decease in fecundity. This situation is exacerbated by contemporary cultural expectations, leading to an increasing number of couples seeking help after only six to eight months of unwanted non-conception. Under increasing pressure from their patients, WM practitioners tend to investigate female infertility too early, with the danger of false positive test results, leading to unnecessary overtreatment, which may expose women to unnecessary medical complications and unnecessary expense. (Brosens, et al., 2004; Gnoth et al, 2005)  While WM may have superior diagnostic capabilities, it has limited tools available to assist the subfertile couple. On the other hand, TCM appears to be much better equipped, with its emphasis on supporting normal healthy bodily and mental functioning.    

Owing to the difficulty in establishing whether a woman is truly infertile or only sub-fertile, this article uses the term ‘infertility’ to cover both clinical scenarios. It is also unfortunate that the currently accepted medical definition of ‘infertility’, does, in fact include both. I say ‘unfortunate’ because many women are encouraged to seek expensive and possibly risky treatments for ‘infertility’, when the majority would become pregnant in due course, without any outside assistance. These matters are the subject of an ongoing debate within the medical profession. (Gnoth et al., 2005)

INFERTILITY IN WESTERN MEDICINE

Up until recently infertility was defined as the inability to conceive after 2 years of unprotected sexual intercourse. (European Society for Human Reproduction and Embryology, 1996) More recently the time limit has been truncated, (Hall, 2007, Jairo, Nelson & Wallach, 2006; Al-Inany, 2005) most likely due to the tendency in developed countries to delay procreation. In these populations 80–90% of couples attempting to conceive are successful after 1 year and 95% after 2 years. (Brosens, et al., 2004; Gnoth et al, 2005)  This trend towards a delay in child-bearing has important implications because of an age-related decrease in fecundability, which begins at age 35 and is exacerbated after age 40. Currently, about 17% of couples in developed countries seek medical advice for infertility. (Cahill & Wardle, 2002).[1]

The implications of the above statistics for a couple seeking assistance with pregnancy after less than one year of trying are as follows:

• They are likely to be part of the 20% who do not achieve pregnancy within this time (assuming that 80% of couples will be successful after six months of fertility timed intercourse)
• Of these couples, around 25% (5% out of 20%) will be truly infertile and in most of these a cause will be found.
• The remaining 75% of these couples will eventually achieve a pregnancy, and will be found, retrospectively (and only retrospectively) to have been subfertile but not truly infertile.[2]

Causes if infertility

Various authors give slightly different figures for the allocation of causes in infertility. In order of less recent to more recent, these are:

• ‘10 – 20% of infertility cases are unexplained; the rest are caused by ovulatory failure (27%), tubal damage (14%), endometriosis (5%), low sperm count or quality (19%), and other causes (5%)’. (Al-Inany, 2005)
• ‘Female factors account for 32% of infertility; male factors account for 18.8% of infertility; male and female factors combined cause 18.5% of fertility; and the etiology is unknown in 11.1%, and other causes are identified in 5.6%’. (Jairo, Nelson & Wallach, 2006)
• ‘infertility can be attributed primarily to male factors in 25%, female factors in 58%, and is unexplained in about 17%.’ (Hall, 2007)
• Ovulatory failure (27%); tubal damage (14%); endometriosis (5%); low sperm count (10%); other causes (5%); unexplained (20%) (Bhattacharya et. al, 2010)
• Ovulatory disorders (25%); tubal damage (20%); male factors (30%); uterine or peritoneal disorders (10%); unexplained (no identified male or female cause (25%). Disorders are found in both the man and the woman in about 40% of cases. (NICE, 2013)

It should be noted that the acknowledgement of male factors has gained an increased prominence in recent years.

Normal fertility depends upon the following factors:

• The integrity of the female and male reproductive tracts
• The release of a normal preovulatory oocyte
• The production of adequate spermatozoa
• The normal transport of the gametes to the ampullary portion of the fallopian tubes for fertilization
• The subsequent transport of the cleaving embryo up to the endometrial cavity for its normal implantation and further development.

Disruption at any of these levels will lead to the inability of a couple to conceive or have a normal pregnancy. The three major known mechanisms underlying female infertility are ovulatory failure, tubal damage and endometriosis. In addition various drugs, such as, non-steroidal anti-inflammatory drugs (CSM, 2006; Aronson, 2006) can reduce fertility.

The main etiologic factors associated with an increased risk of infertility include pelvic inflammatory disease (PID); endometriosis; environmental and occupational factors; toxic effects related to tobacco, marijuana, or other drugs; excessive exercise; inadequate diet associated with extreme weight loss or gain; and advanced age. (Jairo, Nelson & Wallach, 2006)

Initial Evaluation of Infertile Couples

In all couples presenting with infertility, the initial evaluation includes discussion of the appropriate timing of intercourse and discussion of modifiable risk factors such as ‘recreational’ drug use (e.g. tobacco, cannabis and alcohol), caffeine intake and obesity. A description of the range of investigations that may be required and a brief description of infertility treatment options, including adoption, should be reviewed. Initial investigations are focused on determining whether the primary cause of the infertility is male, female, or both. These investigations include a semen analysis in the male, confirmation of ovulation in the female (measurement of mid-luteal phase progesterone), and, in the majority of situations, documentation of tubal patency in the female. Although frequently used in the past, recent studies have not supported the efficacy of postcoital testing of sperm interaction with cervical mucus as a routine component of initial testing. In some cases, after an extensive evaluation has excluded identifiable male or female causes of infertility, the disorder is classified as unexplained infertility. (Hall, 2007)

Ovulatory Failure

Ovulation may be inhibited due to various factors, e.g. PCOS, adenoma in the anterior pituitary, thyroid disorders and adrenal disorders (NICE, 2007). Treatments for women in whom this has been detected include the following:

1. Clomifene.
2. Tamoxifen
3. Metformin.
4. Cyclofenil.
5. Gonadotrophins (human menopausal gonadotrophin, recombinant follicle-stimulating hormone)
6. Gonadotrophin releasing hormone (gnrh) agonists plus gonadotrophins.
7. Gonadotrophin releasing hormone (gnrh) antagonists.
8. Ovarian wedge biopsy. .
9. Laparoscopic ovarian drilling.
10. Pulsatile gonadotrophin releasing hormone. .
11. In vitro fertilization (IVF)
12. Intrauterine insemination (IUI) plus controlled ovarian stimulation.
13. Gonadotrophin priming of oocytes before in vitro maturation.

Out of these Clomifene, IVF and Metformin are likely to be beneficial. Gonadotrophins are likely to cause adverse events such as multiple pregnancies or ovarian cancer. The efficacy of the other treatments is at present unknown. (Al-Inany, 2005; Bhattacharya et. al, 2010)

Tubal Damage

Tubal damage is primarily due to previous pelvic surgery or endometriosis. (NICE, 2007). Treatments for women in whom this has been detected include the following:

1. Selective salpingography plus tubal catheterisation.
2. Tubal flushing with oil soluble media.
3. Tubal flushing with water soluble media.
4. Tubal surgery.
5. IVF

Of the above treatments, in IVF has been shown to be beneficial, while tubal flushing with oil soluble media and tubal surgery before IVF are likely to be beneficial. Selective salpingography plus tubal catheterization and tubal flushing with water soluble media are of unknown benefit. (Al-Inany, 2005; Bhattacharya et. al, 2010)

Endometriosis

Endometriosis may be suspected from the case history and physical examination, and it is confirmed by laparoscopic examination. (Kapoor & Davila, 2007).

Treatments for women in whom this has been detected include the following:

1. Drug-induced ovarian suppression.
2. IUI plus gonadotrophins.
3. Laparoscopic ablation.
4. IVF
5. Tubal flushing

Of the above treatments, IVF, intrauterine insemination plus gonadotrophins, laparoscopic ablation of endometrial deposits and tubal flushing are likely to be beneficial. Drug-induced ovarian suppression is likely to be ineffective or harmful. (Al-Inany, 2005; Bhattacharya et. al, 2010)

Outcomes of Western treatments for Infertility with known cause

1. IVF: 21.8% live birth rate per treatment cycle. If the woman’s age is less than 38 years this is increased to 25.1%. After five attempts, approximately 50% of women under 34 years will have conceived. (NICE, 2007).[3]
2. Tubal surgery: 5% – 50% depending on the initial extent of tubal damage. (NICE, 2007).
3. Clomiphene citrate:  With the achievement of 3 consecutive ovulatory cycles, 40-50% of women will become pregnant. However, endometrial thinning, which is associated with a lowered pregnancy rate in IVF cycles, is a possible adverse event. (Petrozza & Styer, 2006).

Treatment outcomes for cases with unexplained infertility (from Petrozza & Styer, 2006)

PROTOCOL	PREGNANCY RATE, %
No treatment	1.3-4.1
IUI alone	3.8
Clomiphene with timed coitus	5.6
Clomiphene with IUI	10
Gonadotropins with timed coitus	7.7
Gonadotropins with IUI	17.1
IVF	35-50

Thus, IVF is the treatment of choice in these cases.

In vitro fertilization (IVF)

IVF is also known as assisted reproduction technology (see Appendix 2). It is extremely difficult to get an idea of potential outcomes in IVF as different authors used different end points (i.e. some used pregnancy, and others live births). Moreover, the figures quoted were sometimes per cycle and sometimes per couple (presumably over several cycles until a pregnancy was achieved or, in the cases that were unsuccessful, until the couple gave up) and sometimes it was not specified.  The most recent NICE guidelines avoid giving any estimates for outcomes and simply provide some relatively meaningless charts[4] that reveal the fact that after age 36 the live birth rates for IVF decline sharply.

The outcomes of IVF treatment, in terms of live deliveries per embryo transfer cycle, vary considerably depending on age.

• 30 – 34 years: 32.8%
• 35-39 years: 23.1%
• 40 – 44 years: 9.2%

(Macaldowie, Lee, Chambers, 2015)

The overall success rate for a course of IVF treatment in 2010 was 35.4%, with the average number of cycles of IVF needed to achieve a live birth, being 1.3 cycles (in the UK). (The Human Fertilization and Embryology Authority, 2010)

Although some couples may continue for up to nine cycles if they have been unsuccessful, the generally accepted number of IVF cycles is three to five. By the third cycle around 70 – 90% will result in a live birth, and after the fifth there is minimal increase in successful outcomes. (Macaldowie, Lee, Chambers, 2015; Luke et al., 2012)

INFERTILITY IN TCM

Female fertility depends upon several factors. Firstly the arrival of the tian gui, which is related to the 7 year cyclical development (and orderly decline) of the Kidney Qi in a woman’s body. This has been an essential part of TCM perspective on a woman’s ability to conceive since the time of the Huang Di Nei Jing in the early Han dynastic period.  ‘In general the reproductive physiology of woman is such that at seven years of age her Kidney energy becomes full, her permanent teeth come in and her hair grows long. At fourteen years the tian gui, or fertility essence, matures and the ren and the chong channels responsible for conception open, menstruation begins and conception is possible…..At forty nine years the Chong and the Ren channels are completely empty, and the tian gui has dried up. Hence the flow of the menses ceases and the woman is no longer able to conceive’. (Ni, 1995, p. 2) Other factors which have a strong influence on fertility include an abundant supply of Qi and Blood, absence of pathogenic factors (which may obstruct the chong–ren channels and the uterus), and normal movement of the Qi and Blood, particularly in the lower Jiao. Thus, any disruption to these processes may lead to infertility. (Ye, 2001, p.2; 45-46; Xuan & Li, 1990, p. 260; Maciocia, 1998, pp. 15-18, 25-26)

Early methods of classification for causes of female infertility were based on deficiency and excess syndrome patterns in accordance with the three basic causes of disease (i.e. External, Internal and neither External nor Internal). (Yang 1993, p.391; Ye, 2001, pp.2-4) Contemporary authorities further elaborate on this to distinguish three deficiency and four or five excess types of pathodynamics underlying female infertility. (Maciocia, 1993, pp.695-696; Xuan & Li, 1990, p. 260-268) Other authorities focus on the Western diseases that may cause infertility, classifying each of these according to TCM syndrome pattern identification. (Yu, 1998, pp.55-69; 73-77, 171-177; Yin & Liu, 2000, pp.438-443, 443-447, 454-457; Blue Poppy Enterprises, 2008)

Taking a purely traditional perspective we can describe the following pathodynamics that underlie female infertility:

1. Kidney Essence deficiency: predominantly Kidney Yin deficiency or Kidney Yang deficiency. Having sufficient Kidney Essence is crucial, as it underlies every aspect of a woman’s ability to conceive and to nurture the growing fetus.
2. Blood deficiency: including Liver Blood deficiency, and Qi-Blood dual deficiency. In this scenario the uterus and the chong-ren channels lack the nourishment required to nurture the fertilized ovum.
3. Liver Qi constraint: leading to Qi stagnation and/or Blood stasis which affect the chong–ren channels and the uterus.
4. Internally generated pathogens, which obstruct the uterus and the chong-ren: Phlegm-Damp, Damp-Heat, Cold due to Yang deficiency.
5. Exogenous pathogens, which obstruct the uterus and the chong-ren: Cold (the most common one), summer-Heat, Damp-Heat.

Acupuncture and IVF

Considering that IVF is the major treatment option for all types of female infertility, (as discussed above) it would be advantageous if acupuncture were to improve the outcome of this procedure. The results of trials so far are mixed: some positive (e.g. Dieterle et al., 2006; Westergaard et al., 2006) and some negative. (e.g. Smith et al, 2006; Wang et al, 2007) Thus, a recent review concluded that that ‘Limited but supportive evidence from clinical trials and case series suggests that acupuncture may improve the success rate of IVF and the quality of life of patients undergoing IVF and that it is a safe adjunct therapy.’ (Anderson et al., 2007)

Chinese Herbal Medicine

Dharmananda provides a review of Chinese studies conducted up to 1996:

‘clinical studies conducted in China indicate that about 70% of all cases of infertility (male and female) treated by Chinese herbs resulted in pregnancy or restored fertility. Depending on the particular study and the types of infertility treated, success rates ranged from about 50% up to more than 90%. Included in these statistics are cases of infertility involving obstruction of the fallopian tubes, amenorrhea, absent ovulation, endometriosis, uterine fibroids, low sperm count, non-liquefaction of semen, and other causes. In China, due to the greater experience with using herbs, the ability to directly integrate traditional and modern methods of therapy, and the willingness of individuals to consume relatively large doses of herbs, the success rates are probably somewhat higher than can be achieved in the U.S. at the present time. Nonetheless, U.S. practitioners have had many experiences of success in treating infertility…… In the Chinese clinical studies, daily or periodic use of herbs usually resulted in restored fertility within three to six months. Many Chinese doctors feel that if pregnancy is not achieved within about eight to nine months, then it is unlikely that the treatment will be successful with continued attempts. In Japan, where doctors give lower dosages of herbs and are restricted to using a smaller range of herbs, treatment time is usually longer: from six to fifteen months. In the U.S., nearly the full range of Chinese herb materials are accessible, but the dosage to be used is usually lower than in China; as a result, it is estimated that pregnancy can be achieved within six to twelve months. It must be remembered, however, that approximately one-third of infertility cases may fail to respond to all reasonable attempts.’ (Dharmananda, 1996)

It is reasonable to assume that these observations apply equally in an Australian clinical setting.

Recent studies on Chinese herbal treatments coming out of China, although lacking the methodological rigor of Western trials, may in fact provide a model that more realistically represents the clinical scenarios and treatment strategies of Western TCM practitioners (some examples are given below).

Integration of WM and TCM

Given the high costs of the common Western treatments (e.g. IVF, tubal surgery) it would be advantageous if results could be improved through combining with TCM therapies. There is a burgeoning body of research in China based on WM diagnostic categories of female infertility. Many of such reports involve the comparison of standard WM treatments with the same treatment augmented by CHM or acupuncture. Although most of these trials do not meet Western standards, there is some indication that a combined TCM and WM approach may produce superior results. While the magnitude of such results is uncertain, the following examples of recent research lend support to this idea.

1. Chinese herbal medicines that tonify the Kidney and activate Blood circulation together with tubal surgery. (Jiang et al., 2006)
2. Acupuncture on the point Shenque (CV- 8) with tubal surgery. (Huang, 2005)
3. Chinese herbal medicine with clomiphene in cases of PCOS that are resistant to clomiphene. (Yang & Zhang, 2005).
4. Chinese herbal medicine with clomiphene. (Ma et al., 2005)
5. Chinese herbal medicine that tonify the Kidney and activate the Blood circulation with clomiphene in Stein-Leventhal syndrome. (Shao et al, 2004)
6. Chinese herbal medicine with IUI. (Lian et al, 2002)

In addition, some Chinese studies highlight the possibility that Chinese herbal treatment may provide at least as good a result as some Western therapies, e.g.

Chinese herbal medicine for nourishing the Blood and tonifying the Kidney compared with clomiphene (Xia et al., 2004); Chinese herbal medicine to tonify the Kidney and resolve Blood stasis for infertility due to endometriosis (Liu et al, 1998)

Considerably more and better research is needed in the future to confirm the above findings, following which we may see an increased co-operation between Western obstetricians and TCM practitioners. At present it is the decision of the woman (possibly informed by her TCM practitioner) whether or not to opt for TCM, Western or combined therapies. In comparison to the high cost of Western treatments for infertility and the uncertain outcomes (e.g. for IVF: a five months course can cost in the region of $20,000 and still only offers around 50% chance of pregnancy) a preliminary course of TCM treatment over the same time period is a safe and much less expensive option (i.e. the cost would be less than $1800, counting $30 per week for herbs and $60 consultation fee over 20 weeks). Thus, in accordance with the present state of our knowledge, if the initial TCM treatment is not successful, say over 6-12 months, it may be advantageous for the woman to try combined Western and TCM therapy.

APPENDIX 1

A generalised TCM approach to treatment using prepared herbal formulas

As discussed above, one or more of the following pathodynamic factors may underlie female infertility:

1. Kidney Essence deficiency: either Kidney Yin deficiency or Kidney Yang deficiency
2. Blood deficiency: including Liver Blood deficiency, and Qi-Blood dual deficiency
3. Liver Qi constraint: leading to Qi stagnation and/or Blood stasis
4. Internally generated pathogens: Phlegm-Damp, Damp-Heat, Cold due to Yang deficiency.
5. Exogenous pathogens: Cold (most commonly), summer-Heat, Damp-Heat.

In general, women with a mild to moderate degree of Qi-Blood deficiency or Liver constraint, are more likely to be subfertile. On the other hand women with pronounced features of Blood stasis and/or Kidney Essence deficiency are more likely to be truly infertile – and hence require a longer treatment course as well as a realistic prognosis i.e. she should be prepared to accept that the outcome may not be favorable.

Kidney Essence deficiency (Yang deficiency type)

Long menstrual cycle, cold signs (intolerance of cold, cold extremities and lower abdomen), urination is copious and clear, tongue is pale swollen and moist

pulse is deep, weak and slow; general signs of Kidney Yang deficiency, e.g. sexual hypofunction (low libido, lack of vaginal secretions), low back pain with a cold sensation, cold knees, weakness of the legs and knees, severe fatigue.

P/T:   Warm-tonify the Kidney Yang and enrich the Kidney Essence to nourish the Chong and Ren Channels.

Select one or more of the following:

Ba Ji Yin Yang Wan (Morinda Combination)

You Gui Wan (Right Returning Formula)

MOTHERHOOD FORMULA (Nuan Gong Cheng Yun Fang)

MOTHERHOOD 2 FORMULA (Yang Shen Cheng Yun Fang)

Kidney Essence deficiency (Yin deficiency type)

Early menstruation (i.e. short cycle), dry mouth, night sweating, red tongue with little or no coat, thread-rapid pulse. General signs of Kidney Yin deficiency (e.g. dry vagina, dizziness, tinnitus, pain and weakness of the low back and knees, night sweating, heat in the five centers, malar flush, afternoon fever, dry mouth).

P/T:   Nourish the Kidney Yin and enrich the Kidney Essence.

Zuo Gui Wan (Left Returning Formula)

Plus

Si Wu Wan (Dang-gui Four Combination) a.k.a. NOURISH THE BLOOD FORMULA

Qi-Blood dual deficiency

Scanty menstrual flow, which is pale in colour, pale or sallow complexion, fatigue, muscular weakness, poor appetite, loose stools and other signs of general Qi-Blood deficiency (e.g. pale tongue with a thin white coat, thread-weak pulse).

P/T:    Tonify the Qi and nourish the Blood

Shi Quan Da Bu Wan (Ginseng & Dang-gui Ten Formula)

OR

QI & BLOOD TONIC FORMULA (Ren Shen Yang Rong Tang)

Variation:

• With history or prior miscarriage or with threatened miscarriage.

MOTHERHOOD FT-2 FORMULA (An Gong Gu Tai Fang)

• With stress and emotional strain

+ Xiao Yao San (Bupleurum & Dang-gui Formula) a.k.a. STRESS RELIEF 2 FORMULA

Liver constraint, Qi stagnation

Irregular menstruation, lower abdominal pain before and during menstruation, breast distension and pain before the period (i.e. PMS), depressed mood, irritability, stress and emotional strain, discomfort in the hypochondria and/or chest, wiry pulse.

P/T:   Soothe the Liver and relieve constraint, regulate menstruation (by regulating the Qi and Blood).

Xiao Yao San (Bupleurum & Dang-gui Formula) a.k.a. STRESS RELIEF 2 FORMULA

Plus

Tao Hong Si Wu Wan (Persica, Carthamus & Dang-gui Combination) a.k.a. BLOOD MOVING 2 FORMULA

Phlegm-Damp retention

Overweight or obesity, prolonged menstrual cycle with scanty flow, greasy tongue coat, slippery pulse. There may also be prolonged menstrual cycle with scanty flow or amenorrhea, excessive vaginal discharge.

P/T:   Resolve Phlegm and dry Damp, regulate the Qi to readjust menstruation

Wen Dan Tang (Bamboo & Hoelen Formula) a.k.a. CLEAR THE PHLEGM FORMULA

Plus

Chai Hu Shu Gan Wan (Bupleurum & Cyperus Combination) a.k.a. QI MOVER FORMULA

Qi stagnation and Blood stasis

Irregular or infrequent periods, dark menstrual flow with clots, dysmenorrhea, premenstrual syndrome, low back pain, fatigue, pale complexion, tongue is dark or purple or may have dark spots, pulse is choppy or wiry and may also be thready and deep. There may also be a long menstrual cycle.

P/T:   Activate the Blood and dispel stasis, regulate menstruation.

MOTHERHOOD FT-1 FORMULA (Cu Luan Cheng Yun Fang)

Cold in the Uterus

Long menstrual cycle with scanty bleeding and small clots, dysmenorrhea that is alleviated by the application of heat, sensations of cold, pallor, low back pain,  tongue is pale with a thick white coat, pulse is weak-taut or choppy. There may also be hot flushes (in spite of feeling cold).

P/T:  Warm –tonify the Kidney Yang and warm the Uterus to dispel Cold

Wen Jing Tang (Dang-gui & Evodia Formula)

How long to continue treatment

Based on reports from practitioners, the treated woman generally falls pregnant within three to nine months, and the establishment of a normal, regular menstrual cycle is usually the first indication that there will be a positive outcome. Once there is evidence of a pregnancy the treatment protocol should be reviewed. In cases with ‘morning’ sickness, treatment should be directed primarily towards promoting normal digestion, and tonifying formulas should be minimized or avoided as they may aggravate this condition.

Practitioners who have been taught that all Blood-moving herbs should be avoided in pregnancy may fear that even formulas that contain relatively mild Blood-moving ingredients, such as Angelica polymorpha (dang-gui) and Ligusticum wallichii (chuan xiong), may carry an increased risk of harming the embryo or fetus if taken for too long, especially during the time that conception has actually occurred and the time that the woman discovers that she is pregnant. However, in clinical practice this is not the case. In the gynecology departments of Chinese hospitals, the use of these herbs is common, both before pregnancy and in the early stages. Moreover, there is no clinical evidence that the commonly used Blood-moving herbs (as used in the above formulas) cause any harm when taken during pregnancy.

APPENDIX 2

Assisted Reproductive Technologies (ART)

(From: Assisted Reproductive Technology in Australia and New Zealand, 2013)

‘Assisted reproductive technology (ART) is a group of procedures that involve the in vitro (outside of body) handling of human oocytes (eggs) and sperm or embryos for the purposes of establishing a pregnancy. Each ART treatment involves a number of stages and is generally referred to as an ART treatment cycle. The embryos transferred to a women can either originate from the cycle in which they were created (fresh cycle) or be frozen and thawed before transfer (thaw cycle).’

‘A typical fresh in vitro fertilization (IVF) cycle involves the following five steps:

1. Controlled ovarian stimulation during which an ovarian stimulation regimen, typically using follicle stimulating hormone (FSH), is administered to a woman over a number of days to induce the maturation of multiple oocytes 
2. Oocyte pick-up (OPU) where mature oocytes are aspirated from ovarian follicles
3. Fertilization of the collected oocytes using the woman’s partner or donor sperm 
4. Embryo maturation during which a fertilized oocyte is cultured for 2–3 days to form a cleavage stage embryo (6–8 cells) or 5–6 days to create a blastocyst (60–100 cells).
5. Transfer of one or more fresh embryos into the uterus in order to achieve pregnancy.’

‘Over the last three decades, ART has evolved to encompass complex ovarian hyperstimulation protocols and numerous variations to the typical fresh IVF treatment cycle described above. Some of these variations include:

• Intracytoplasmic sperm injection (ICSI), when a single sperm is injected directly into the oocyte
• Assisted hatching, when the outer layer of the embryo, the zona pellucida, is either thinned or perforated in the laboratory to aid ‘hatching’ of the embryo
• Gamete intrafallopian transfer (GIFT), when mature oocytes and sperm are placed directly into a woman’s fallopian tubes so that fertilization may take place in vivo (inside the body). While once popular, this procedure now accounts for only a very small percentage of ART cycles
• Preimplantation genetic diagnosis (PGD), when one or more cells are removed from the embryo and analysed for chromosomal disorders or genetic diseases
• Oocyte donation, when a woman donates her oocytes to others 
• Oocyte/embryo recipient, when a woman receives oocytes or embryos from another woman
• Cryopreservation and storage of embryos that are not transferred in the initial fresh treatment cycle. Once thawed or warmed, the embryos can be transferred in subsequent treatment cycles. Cryopreservation techniques include both the traditional slow freezing method and a newer technique called ‘vitrification’. Vitrification can be used to cryopreserve gametes and embryos, and uses an ultra-rapid temperature change with exposure to higher concentrations of cryoprotectants
• Cryopreservation and storage of oocytes and embryos for fertility preservation 
• Surrogacy arrangements, where a woman, known as the ‘gestational carrier’, agrees to carry a child for another person or couple, known as the ‘intended parent(s)’, with the intention that the child will be raised by the intended parent(s).

Along with ART, a number of other fertility treatments are undertaken in Australia and New Zealand. Artificial insemination is one such treatment by which sperm are placed into the female genital tract (for example, intracervical or intrauterine), and can be used with controlled ovarian hyperstimulation or in natural cycles. Artificial insemination can be undertaken using a partner’s sperm, or donated sperm, also known as ‘donor sperm insemination’ (DI).’

(Macaldowie, Lee, Chambers, 2015)

How many cycles?

(From: Cumulative Birth Rates with Linked Assisted Reproductive Technology Cycles, 2012)

Data collected for the period from 2004 through 2009 from the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System (CORS) database, from clinics providing assisted reproductive technology in the United States.

‘The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used.’

‘Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment.’ (Luke et al., 2012)

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[1] Please note that the figures vary from study to study and, as some are retrospective, there is a considerable margin for error. I would therefore advise that you read any statistics related to fecundity as ±10%. The figures given by the NICE, 2013 on causes of infertility, in the next section, are a good example (add them up!). As all of the figures in this article have been gathered from various sources, the same advice also applies.

[2] The attentive reader will have spotted the good news here: in most cases the couple will achieve pregnancy regardless of whether or not they receive a treatment, or, indeed a medical investigation and a diagnosis. The bad news is that the statistics will never be able to inform a clinician whether or not a particular couple will be able to achieve a pregnancy followed by a live birth.

[3] With the recent improvements in technique, these figures are now a little higher (see below and Appendix 2)

[4] ‘Relatively meaningless’ from the couple’s point of view. In this connection I am reminded of the statement by John Ioannidis (2005): ‘… for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias.’ This would also apply to clinical practice guidelines that are based on such research findings.