This chapter should be cited as follows:
Ashiru OA, Loto OM, et al, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.421073

The Continuous Textbook of Women’s Medicine Series – Gynecology Module

Volume 15

Reproductive medicine for the obstetrician and gynecologist

Volume Editors: Professor Luca Gianaroli, S.I.S.Me.R. Reproductive Medicine Institute, Italy; Director of Global Educational Programs, IFFS
Professor Edgar Mocanu, RCSI Associate Professor in Reproductive Medicine and Surgery, Rotunda Hospital, Ireland; President, IFFS
Professor Linda Giudice, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, USA; Immediate Past President, IFFS

Published in association with the
International Federation of
Fertility Societies

Chapter

Female Infertility

First published: November 2024

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INTRODUCTION

Infertility is defined as a disease of the reproductive system in which there is the inability to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse by a heterosexual couple.¹

Infertility could be primary or secondary. In primary infertility, the couple has never achieved a pregnancy, while in secondary infertility, the couple has had at least one previous pregnancy, irrespective of the outcome. The chances of spontaneous conception in any given menstrual cycle are less than 20%. The cumulative probability of conception, however, increases with the duration of cohabitation, from about 25% in the first month to about 85% at the end of the first year.²

Large numbers of people are affected by infertility in their lifetime, according to a new report published by the WHO. Around 17.5% of the adult population – roughly 1 in 6 worldwide – experience infertility, showing the urgent need to increase access to affordable, high-quality fertility care for those in need. The new estimates show limited variation in the prevalence of infertility between regions. The rates are comparable for high-, middle-, and low-income countries, indicating that this is a major health challenge globally. Lifetime prevalence was 17.8% in high-income countries and 16.5% in low- and middle-income countries.³

Causes of infertility may be related to the female partner, the male partner, or both. There may be no abnormality in about 10% of the couples with infertility after undertaking the basic investigations, and this is termed unexplained infertility. The major female causes of infertility are utero-tubal and anovulatory factors, while abnormalities in sperm quality and concentration are the male causes.

HISTORY TAKING IN PATIENTS WITH INFERTILITY

History taking in infertility aims to identify the point in the hindered reproductive process and elucidate the possible pathology leading to the impediment in conception. The main events in conception are ovulation, fertilization, and implantation. Any condition that prevents these processes may result in infertility. After obtaining the biodata of the couple, taking note of the age of the woman and the man and the duration of infertility, efforts are made to identify the possible pathology resulting in infertility.

At the first consultation, the couple should be seen together to obtain the history so that they can corroborate each other in the history that is obtained, after which they may be seen apart to delve into more sensitive matters that a spouse may not want to disclose to the partner as yet, if necessary. The essential aspects of the history include the following:

• Coital frequency
  There is a positive correlation between the frequency of coitus and pregnancy rates. Coitus once per week gives an approximate probability of conception in 6 months of 17%, while it increases to 50% for coital frequency of thrice a week.
• Knowledge of ovulation
  It is essential to ask the couple if they have knowledge of the ovulation period and whether they time sexual intercourse accordingly. Spermatozoa survive for about three days in the female genital tract, while the ovum survives for about 24 hours. The fertilization window is about four days around the ovulation period.
• Menstrual history
  An irregular menstrual pattern makes it difficult to predict the ovulation period and may be a pointer to anovulation. Most women with polycystic ovary syndrome (PCOS) have irregular menstruation. The history of milky breast discharge associated with amenorrhea suggests hyperprolactinemia. Absent menstruation may indicate ovarian failure or the onset of menopause. Severe menstrual pain may be an indication of endometriosis. Superficial and deep dyspareunia may also suggest a pelvic pathology. A history of heavy menstrual bleeding may be a pointer to submucous fibroids.
• Previous pelvic surgery
  History of previous pelvic surgery may be a pointer to compromise of the fallopian tubes or the endometrium. These include surgical procedures like previous myomectomies, ovarian cystectomies, ectopic gestation, appendicitis, or even cesarean sections, as well as complicated dilatation and curettage (D&C) for termination of pregnancy. In males, some surgeries may also predispose to infertility, especially when complicated, including herniotomy, orchidopexy, and herniorrhaphy.
• Previous pregnancy
  Relevant history of pregnancies with current or prior partners should be obtained, including events in the pregnancy and labor; the history should include details about termination of pregnancies and complications, prolonged rupture of membranes and prolonged labor, manual removal of placenta, cesarean section, puerperal sepsis, and complicated wound healing process. Also, the history of whether the man has fathered children outside this relationship is essential.
• History of pelvic inflammatory disease (PID) and sexually transmitted infections (STIs)
  History suggestive of the above may be a pointer to tubal factor infertility. A history of lower abdominal swelling may indicate uterine fibroids or ovarian masses.
• Male partner history
  The male partner should also be asked about history concerning erectile function, premature ejaculation, previous groin surgery, previous STDs, mumps orchitis, and tuberculosis.
• Medical history
  Medical history of both partners concerning chronic medical illnesses such as diabetes mellitus (DM), hypertension, obesity, and other conditions that require regular drug intake, as well as the side effects of the drugs, are also significant. Symptoms of thyroid dysfunction should also be elucidated, such as heat or cold intolerance.
• History of investigation and outcome
  It is essential to ask about the investigations they have undertaken and the result of such investigations, as this may help to establish trends, response to treatment, and the next line of action.
• History of treatment and outcome
  Any treatment the couple has received before the presentation needs to be inquired into and the outcome. Information about using unorthodox and alternative medicines and inserting corrosive pessaries into the vagina, which often results in gynaetresia, should be obtained. The outcome and contributory factors should be documented for those who had previously undertaken any assisted conception.
• Physical examination
  Following the history, a detailed physical examination is carried out on the couple, which should include a general physical examination taking note of the hair distribution pattern, assessment of the abdomen to detect big fibroid masses as well as ovarian masses, breast examination to exclude galactorrhoea and inspection of the male external genitalia to assess the testes if indicated. A bedside ultrasound scan will complement the examination.

LIFESTYLE AND ENVIRONMENTAL FACTORS

Couples who find it challenging to conceive should be made aware that they must examine their lifestyle, environment, and occupation, and evaluate what needs to be modified to achieve conception. There is growing evidence that lifestyle choices contribute to the overall quality of health and life (QoL), reflecting many potential lifestyle risks widely associated with alterations of reproductive function up to infertility.⁴ Recently, female fertility problems and spontaneous miscarriages have increased, and it has become a matter of particular concern among women of childbearing age. The rise in adverse reproductive health outcomes above is partly attributed to exposure to hazardous factors ubiquitously in the environment and workplace.⁵ Some of these factors are listed below and further discussed in details in subsequent chapters:

• Dietary
• Substance abuse
• Exercise
• Environmental toxins-I Endocrine Disruptor Chemicals (EDC)
• Environmental toxins-II (oil & gas)
• Household dust
• Industrial waste

Comprehending the detrimental impact of environmental pollutants on reproductive health has led to notable advancements, including the development of testing techniques for detecting these toxins and the adoption of modern Mayr medicine as a holistic approach to effectively mitigate their effects and promote better reproductive well-being.^6,7

AGING AND FERTILITY

It is an established fact that females are born with all the oocytes that they will have throughout their lifetime, and additional oocytes cannot be created after birth. These oocytes experience a reduction in quantity right from in-utero till menopause sets in. There is also the hypothesis that there is an accompanying decline in quality as well, over the years, and this is believed to be responsible for the higher incidence of chromosomal abnormalities in children born to women older than 35 years old.^8,9

Follicular depletion

The female baby while in utero has 600,000 germ cells at about 2 months old and this number peaks at 7 million at about 5 months. The number then gradually declines to 2 million at birth and 400,000 at the onset of puberty.^8,10

Endocrinology of aging

The peptides such as LH and FSH, as well as steroids like estrogen, progesterone are the hormones largely responsible for the control of reproduction in females. The hormone levels are usually quiescent until pulsatile release of GnRH signals the onset of puberty via secretion of pituitary peptides, which subsequently leads to the production of ovarian steroids.^8,10

In very simplistic explanation, at the onset of every menstrual cycle, FSH is secreted leading to gradual recruitment of primary oocytes, one of which becomes the dominant follicle while the others become atretic. The gradual increase in growth of the follicle under the action of FSH leads to increase in the quantity of estrogen elaborated by the growing follicle. The increasing estrogen levels serve as negative feedback to the FSH, leading to lower levels of FSH and withdrawal of support for the other follicles recruited in that cycle.

Thus, at the onset of the menstrual cycle, FSH and estrogen levels are at their lowest. High basal level of FSH at the beginning of the menstrual cycle thus signifies absent negative feedback due to absent growing follicles that can elaborate enough estrogen to suppress the FSH levels. In a similar vein, AMH levels are low when there’s a depletion in the quantity of primary oocytes in the ovary, because there are not enough of the oocytes secreting AMH.^8,9,10

Genetics of reproductive aging

Aging in female mammals is associated with reduced oocyte quantities in the ovary, reduced quality of the oocytes and higher chances of chromosomal anomalies.¹¹

Considering reproductive aging is an aspect of overall aging, it has been propounded that the passing of time leads to the inability of the body to repair damage at the genetic level, thus accounting for the decline in the quality of oocytes as well as increased risk for chromosomal anomalies.^8,10,12,13

ASSESSMENT OF OVARIAN RESERVE

Ovarian reserve and reproductive aging

Female fertility declines with age. The ovary contains a finite number of eggs, which decreases exponentially with age.¹⁴ The decline in ovarian reserve becomes more pronounced and accelerated, especially in the late 30s and early 40s.^14,15,16 Aside from age, the ovarian follicular pool is also further influenced by other factors, including genetics, race/ethnicity, ovarian surgery/diseases, chemotherapy, and exposure to environmental pollutants.^16,17 At birth, the ovary is estimated to contain about 2 million eggs, which declines to about 200–400 thousand at menarche (10–13 years of age); and about a few thousand at age 50–51 at menopause.^14,16 The older a woman becomes, the lesser the number of eggs she has in reserve and the higher the number of poor-quality eggs she possesses in her ovary. There is a strong correlation between the age of a woman and the quantity and quality of her eggs.¹⁶ It has been proven by epidemiologic and scientific research.¹⁷ With increasing female age, apart from infertility and declining ovarian reserve, the closer a woman gets to menopause, the risks of menstrual irregularities, abnormal uterine bleeding, uterine pathologies like fibroids, and risks of miscarriage are higher.^18,19 Poor ovarian response is associated with increased female age, a significant decline in the quality and quantity of oocytes in the ovary, and a reduced chance of spontaneous pregnancy or following IVF. Therefore, accurate prediction of ovarian response could be of value in triaging women into poor-, normal- and hyper-responders to mitigate individualization of ovarian stimulation protocols, initiate cost-effective IVF interventions (when necessary), and avoid outcome complications like OHSS in hyper-responders.²⁰

Ovarian reserve test (ORT)

Ovarian reserve tests predict ovarian reserve reproductive potential and ovarian response to control ovarian stimulation COS. ORT does not indicate conception spontaneously or through assisted reproduction.^20,21 The lower the ovarian reserve, the lower the likelihood of achieving pregnancy spontaneously or with ART stimulation. Ovarian reserve estimates are also valuable to predict or estimate the dose of gonadotropin in ART, making tailored, risk-free, individualized treatment regimens possible. ORTs, including anti-Müllerian hormone (AMH) blood test, ultrasound scan estimation of the number of follicles in the ovary (antral follicular count, AFC), and ovarian volume, are reported as the most reliable markers of ovarian reserve. In the literature, several research studies reported AMH, AFC, and ovarian volume as the best markers of ovarian reserve, in contrast to basal D2 to 3 FSH/E2 and inhibin B.^22,23 AMH and AFC, in particular, accurately reflect the quantity and functional capacity of the ovary.^22,23 However, FSH, E2, and inhibin-B are now regarded mainly as poorer markers of ovarian reserve assessment and are often unreliable. A decisive advantage supporting the use of AMH as a measure of ovarian reserve is the fact that it does not fluctuate throughout the menstrual cycle, in contrast to FSH, LH, and estradiol, which have fluctuating personal, interpersonal, and significant intra- and inter-cycle variabilities.²⁴ Ovarian reserve tests include biochemical tests and ultrasound imaging of the ovaries.²² Biochemical tests of ovarian reserve can be divided further into early-follicular-phase measurements of FSH, E2, or inhibin B; serum AMH measurement, which is cycle-day-independent and dynamic ovarian reserve tests, including clomiphene citrate challenge test (CCCT) EFORT, and GAST.

Static biochemical ORT

Basal FSH and E2 concentration

Biochemical measures of ovarian reserve are intended to directly or indirectly measure the follicular pool.²⁵ Basal serum FSH, LH, and E2 levels in the follicular phase of the menstrual cycle are low. They are often used to test ovarian reserve to prepare for controlled ovarian stimulation in assisted reproduction. On days 2, 3, or 4 of the menstrual cycle, FSH and LH gradually increase in the follicular phase, leading to the resumption and growth of a cohort of early pre-antral follicles. The rise in serum E2 and inhibin B secreted by the granulosa cells of the growing follicles leads to negative feedback and a fall in the FSH concentration, resulting in monovulation. In a normally cycling reproductive age woman, the basal serum FSH and LH concentrations on days 2 to 3 are low <10; values >10 can predict DOR.^26,27,28,29 However, because of their intrinsic significant inter- and intra-cycle variability, FSH, LH, and E2 levels have limited value and reliability as a marker of ovarian reserve. In women at about 37–45 with diminished follicular pool and those in the climacteric or menopausal stages, the basal FSH and LH are elevated with a simultaneous decline in the serum concentration of E2. Elevated basal serum FSH and LH in combination with falling E2 levels are specific but not sensitive tests for DOR.^16,30 Also, serum FSH, E2, and inhibin B values in the early follicular phase are unsuitable for predicting infertility, ovarian response to ART stimulation, or outcome.¹⁶ Notably, a serum value above 10 in the follicular phase is associated with DOR and a poor ovarian response to control ovarian stimulation during IVF treatment. Therefore, serum values of FSH >10 can be used to counsel women going for IVF treatment about the likelihood of diminished ovarian reserve and poor response to gonadotrophin stimulation.

Anti-Müllerian hormone (AMH)

Anti-Müllerian hormone belongs to the TGF-β superfamily. It is a homodimeric glycoprotein linked by disulfide bonds with a molecular weight of 140 kDa. It is secreted by the granulosa cells of the primary, preantral, and early antral follicles in contrast to inhibin B, which is secreted by the granulosa cells of the preantral follicles. Both hormones belong to the TGF-β superfamily and are direct measures of the follicular pool in the ovary. AMH levels significantly correlate with AFC and age.^31,32,33,34 It is undetectable in neonates and infants and rises in the reproductive age period in consonant with the size of the ovarian follicular reserve and becomes gradually undetectable during menopause.^35,36 In contrast to FSH, LH, and estradiol, serum values of AMH are reported as the most reliable markers of ovarian reserve because it has no intra- or inter-cycle variabilities. It can, therefore, be used anytime during the menstrual cycle, on its own or combined with antral follicular count (AFC) and ovarian volume.^37,38,39,40 In women using hormone contraceptives, AMH as a marker of the ovarian reserve should be interpreted cautiously, as it may be lower in such situations.⁴¹ AMH serum concentrations do not correlate with the quality of ovarian oocytes, and therefore, it is neither a predictor of clinical pregnancy nor a measure of oocyte quality.^20,21,42 Even though AMH is a reliable predictor of poor and excessive ovarian stimulation with gonadotropins in contrast to age, BMI, FSH, and inhibin B, it is a poor predictor of pregnancy or live birth in IVF.^20,21

Inhibin B

Inhibin B is a heterodimeric glycoprotein released by the granulosa cells of the growing antral follicular pool responsive to FSH. With increasing female age and in women with a diminishing number of recruitable follicular pools or those in or near menopause, inhibin B secretion declines, leading to a concomitant rise in FSH concentration, a decreased response to ovarian stimulation, and lower fertility potential are observed.^43,44 It negatively inhibits the secretion of FSH in the anterior pituitary and is regarded as a better predictor of ovarian activity rather than a reliable marker of ovarian reserve and infertility.^44,45,46

Dynamic ovarian reserve tests

Clomiphene citrate challenge test CCCT

CCCT is a dynamic test for ovarian reserve assessment wherein serum FSH and E2 are measured before (cycle day 3) and after (cycle day 10) following oral administration of clomiphene citrate (100 mg daily, on cycle days 5–9). In a woman with normal-responsive ovaries, a rise in serum inhibin B and E2 levels from the growing cohort of ovarian follicles suppresses FSH. However, with DOR, the smaller follicular cohorts available for recruitment will generate less inhibin B and E2 and a decreased negative feedback response, resulting in higher FSH serum levels. Therefore, an elevated FSH concentration after CCCT will suggest DOR. CCCT has a lower sensitivity and is less reliable than ORT compared to days 2–3 FSH and USS AFC measurements for predicting diminished ovarian response, pregnancy, and LB.^28,47 For this reason, it is not a commonly recommended test.^48,49,50

Exogenous FSH ovarian response test (EFORT)

This test is simple and can be used to predict poor responders before IVF treatment, but it cannot reliably predict infertility, ovarian response, and the outcome of IVF treatment. To improve the predictability of the static measurement of D3 FSH to detect a poor responder; improve the clinical efficiency and the outcome of IVF treatment, basal D3 FSH and E2 were measured before administering 300 IU of FSH intramuscularly; 24 h later (on D4 of the menstrual cycle) a repeat serum E2 is measured. Increased serum E2 on D4 >30 pg/ml and basal FSH levels <10–11 predicts a regular responder and DOR if basal FSH is >11 and D4 E2 measurement <30 pg/ml. EFORT is no longer preferred to AMH and AFC, which are now regarded as better predictors of ovarian reserve and are more reliable with no intra- and intercycle variability compared to FSH and E2.^24,47

Gonadotropin agonist simulation test (GAST)

The gonadotropin agonist simulation test (GAST) assesses ovarian reserve by measuring FSH and E2 concentrations on D2–3 of the menstrual cycle before and 2 h after 100 μg GnRH agonist (buserelin injection). GAST gives an indirect estimation of ovarian reserve. A diminished rise in FSH and E2 concentration following the administration of GnRHa in the early follicular phase of the cycle suggests a smaller recruitable ovarian follicle in DOR. Like EFORT, the diagnostic accuracy of GAST is not superior to AMH and AFC; therefore, it is not preferable in most clinical situations as a reliable ovarian reserve test and is not recommended.^47,49,50

Biophysical ultrasonographic measure

Antral follicular count (AFC)

AFC is the sum of the number of antral follicles 2–10 mm in diameter counted during 2D transvaginal ultrasonographic evaluation of both ovaries in the early-follicular phase D2–5 of the menstrual cycle. Several research studies have reported it as a reliable and sensitive predictor of poor ovarian response compared to basal serum values of FSH, E2, and inhibin B or ovarian volume on D2–3 of the menstrual cycle.^22,23 The number of antral follicles counted directly correlates to ovarian response following gonadotropin stimulation. AFC count of 8–10 and >10 reliably predict normal or hyper-response during ovarian stimulation, respectively.³⁴ However, like AMH and other ovarian reserve tests, AFC lacks the sensitivity and specificity to a priori predicting pregnancy or livebirth in spontaneous or assisted reproduction.⁵⁰ AFC has low intercycle variability and high interobserver reliability in experienced centers, and it is a cost-effective and reliable single marker of ovarian reserve or in combination with ovarian volume and AMH.^{31,32,33,34,46}

Ovarian volume

A strong correlation exists between the primordial follicle population and ultrasound ovarian volume.^51,52 OV is measured by transvaginal ultrasonography using the formula the ellipsoid formula (D1 × D2 × D3 × π/6). The volume of each ovary is measured in three perpendicular directions. The sum of the estimated ovarian volume for each ovary is added together to give the basal ovarian volume. With increasing age and decreasing the number of recruitable primordial and antral follicles, especially during menopause, the ovary has a notable volume reduction or atrophies. It forms the basis of its relevance as a measure of ovarian reserve. OV, however, has a high inter- and intra-observer variability. Therefore, it is neither a very sensitive nor a reliable estimate of ovarian reserve and is not commonly recommended.

ROLE OF ULTRASOUND IN THE RADIOLOGICAL INVESTIGATION OF FEMALE INFERTILITY

Imaging is essential in diagnosing female infertility, with pelvic ultrasound as the initial modality followed by HSG for tubal assessment.^53,54 Transvaginal ultrasound offers superior resolution for gynecological evaluations. Advanced techniques like HyCoSy (hysterosalpingo contrast sonography) and 3D/4D ultrasound further enhance diagnostic capabilities, aiding in the detection of endometrial pathologies and congenital uterine anomalies. This section will describe these latest advances in the context of infertility treatment, focusing on sonohysterogram, HyCoSy as an alternative to HSG, and the role of 3D and 4D in diagnosing endometrial pathologies and congenital uterine anomalies.

Saline infusion sonography

Saline infusion sonography (SIS) serves as a valuable adjunct to conventional transvaginal ultrasound, offering enhanced visualization and characterization of endometrial pathologies.⁵⁵ By instilling saline fluid, SIS improves the detection of abnormalities like submucosal myomas, endometrial polyps, and intrauterine adhesions, aiding in the differentiation of lesions and defining their extent within the endometrial cavity. A normal SIS will produce an image like the one in Figure 1. Despite being underutilized, SIS demonstrates comparable precision to hysteroscopy in assessing endometrial lesions, with the added advantages of being minimally invasive, well-tolerated, and cost-effective. As an accessible alternative to diagnostic hysteroscopy, SIS enables better operative planning and patient triaging, addressing the need for safe, affordable, and effective methods for evaluating endometrial pathology.^{55,56,57,58,59,60,61,62} Saline infusion sonography (SIS) is indicated during infertility assessment for cases of poor endometrial visualization with a standard 2D probe or the need to characterize focal lesions, but contraindicated in active pelvic infections, pregnancy, and with intrauterine device presence, with post-procedural infection being the most common complication, advocating some practitioners for routine prophylactic antibiotic use.^58,63 Intrauterine adhesions are a recognized cause of infertility and recurrent pregnancy losses.⁶⁴ Enhanced ultrasonography using SIS helps to differentiate these entities. Examples of sonographic appearance of endometrial pathologies using SIS is presented in Figures 2 and 3.

3D reconstruction of the uterus

In recent times, the addition of 3D has significantly improved the diagnostic value of 2D and even fluid instillation (Figure 4); 3D saline infusion sonography is believed to provide the ultimate image, thereby enhancing diagnostic confidence and accuracy.⁶⁵ There is substantial evidence demonstrating that 3D and 3D SIS yield more accurate results than their 2D counterparts, suggesting their potential to replace conventional 2D ultrasound and saline infusion sonography in evaluating women with infertility, with clear advantages including high patient acceptability and accuracy comparable to hysteroscopy.^{58,61,62,66,67} Examples of images produced with 3D and 3D SIS are shown in Figures 5–8.

Congenital uterine anomalies

Congenital uterine anomalies, stemming from Müllerian duct developmental issues, afflict 8.0–13% of infertile and recurrent pregnancy loss patients, potentially leading to infertility, recurrent miscarriages, and preterm birth. Hysteroscopic septoplasty shows promise in improving pregnancy outcomes. Diagnosis is critical for timely intervention. A consensus advocates 3D ultrasound as the primary diagnostic tool, augmented by MRI, hysteroscopy, and laparoscopy for complex cases. 3D ultrasound offers non-invasive, reproducible, and office-based assessment, positioning it as the preferred method for detecting congenital uterine anomalies.^68,69,70 Image of anomalies identified on 3D positioned alongside their respective diagnosis as illustrated by ASRM Müllerian classification⁷¹ is shown in Figure 9.

Adenomyosis and the junctional zone

Adenomyosis, characterized by ectopic endometrial gland invasion into the myometrium, raises concerns regarding fertility due to its impact on the endometrial-myometrial junction. Research underscores its association with implantation issues, early pregnancy loss, and reduced IVF success rates, particularly in cases with a disrupted junctional zone. The mechanism likely involves altered uterine peristalsis and endometrial receptivity. Routine screening of the junctional zone, especially in adenomyosis patients, is advocated, with 3D ultrasound offering valuable insights into its appearance and thickness alterations, aiding in fertility management.^{72,73,74,75,76} Images of normal and abnormal junctional zones are shown in Figure 10.

Tubal patency assessment

Abnormalities in Fallopian tubes are prevalent causes of female infertility, prompting the necessity for tubal patency assessment early in fertility workup. While traditional methods like HSG have been customary, their limitations have led to the emergence of HyCoSy as a viable alternative. HyCoSy offers comparable diagnostic accuracy, ultrasound pelvis assessment, and enhanced patient comfort, prompting its recommendation as a replacement for HSG. Advances like 3D and 4D HyCoSy, along with innovations like HyFoSy (hysterosalpingo-foam sonography), further enhance tubal assessment. Meanwhile, pelvic ultrasound, especially transvaginal, remains fundamental, with its integration with other modalities streamlining infertility evaluations.^77,78,79,80 Images of tubal assessment using HyFoSy are shown in Figures 11 and 12.

ROLE OF LAPAROSCOPY AND HYSTEROSCOPY IN THE INVESTIGATION OF THE INFERTILE COUPLE

The role of laparoscopy in assessing female infertility extends beyond tubal patency evaluation. It offers direct visualization of pelvic anatomy, enabling the diagnosis of conditions like peritubal adhesions and endometriosis, which may persist despite normal findings on HSG. Laparoscopic assessment provides valuable insights into tuboperitoneal factors contributing to infertility, aiding in tailored management approaches for affected individuals.⁸¹ Figure 13 shows abdominopelvic adhesions at laparoscopy.

Intrauterine pathologies contributing to infertility encompass intrauterine adhesions, submucous fibroids, endometrial polyps, bones in the endometrial cavity and uterine septum.^82,83 Figures 14 and 15 show intrauterine adhesions and bone removal during a hysteroscopy, respectively. Hysteroscopy, regarded as the gold standard for assessing and treating these abnormalities, offers superior diagnostic accuracy and therapeutic potential, often conducted without anesthesia in an office setting.⁸⁴

CONCLUSION

Female infertility evaluation begins with a thorough history, examination, and assessment of ovarian reserve and ovulation. Pelvic ultrasound, particularly 3D ultrasound, is the initial imaging modality for detecting uterine anomalies, followed by HSG for fallopian tube evaluation. Advanced techniques like HyCoSy offer superior results over traditional HSG.

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