Have you conceived naturally before, but now struggle to get pregnant again? You’re not alone — secondary infertility is more common than many realise.
In this webinar, Dr Elias Tsakos, MD, FRCOG – Medical Director of Embryoclinic, Thessaloniki, explained why this can happen, how it’s diagnosed, and what options are available to help you grow your family.
In this presentation, Dr Elias Tsakos explained that secondary infertility refers to difficulty conceiving after a previous pregnancy, regardless of whether that pregnancy ended in a live birth or miscarriage. While definitions vary slightly in medical literature, the core concept remains the same: a pregnancy was achieved in the past, but conception is no longer happening.
Secondary infertility affects couples, single women, and people who previously conceived either naturally or with assisted reproductive technologies. According to Dr Tsakos, these patients are often among the most determined because they have already experienced parenthood and are deeply motivated to have another child.
He also highlighted that secondary infertility is likely more common than statistics suggest, as many couples delay seeking help, assuming that conception will eventually happen again simply because it happened before.
Dr Tsakos pointed out that delayed childbearing plays a major role. Across Europe, the average fertility rate is around 1.4 children per woman, meaning many families stop after one child, sometimes not by choice but because fertility has declined.
Many couples underestimate how much fertility changes with time. “It happened once, so it will happen again” is a common assumption, but age-related fertility decline often makes a second pregnancy much harder to achieve.
Age was repeatedly emphasised as the most significant factor affecting secondary infertility. Dr Tsakos stressed that age matters for both women and men.
In women, increasing age is linked to declining ovarian reserve, reduced egg quality, and higher rates of chromosomal abnormalities. In men, fertility also declines with age. Men over 40 are more likely to experience reduced sperm quality, increased DNA fragmentation, and poorer fertilisation potential, even if standard semen analysis appears normal.
Dr Tsakos noted that sperm analysis alone is not enough to assess male fertility.
It tells us whether sperm can walk, he explained, but not whether they can run.
One of the most important questions Dr Tsakos asks his patients is how long it took to achieve the first pregnancy. Many couples with secondary infertility report that it took several years to conceive the first child.
This often indicates that a mild or moderate fertility factor was already present. When combined with advancing age, that underlying issue can become more pronounced, making conception significantly more difficult the second time.
Dr Tsakos outlined several female-related causes, many of which may already have been present before the first pregnancy.
Tubal factors can arise from infections, adhesions, ectopic pregnancy, or previous surgery. Even subtle tubal damage can affect fertility. Today, advanced ultrasound techniques, such as foam sonography, allow clinicians to assess tubal patency accurately without invasive procedures in most cases.
Uterine factors are often overlooked. Dr Tsakos emphasised that the uterus is more than just endometrial thickness or shape. Conditions such as fibroids, polyps, adhesions, adenomyosis, and even endometrial cancer can affect fertility. With advanced ultrasound technology, many of these conditions can be detected early, sometimes even in women who present simply for IVF.
Chronic endometritis is another important and underdiagnosed cause. It may not always be visible on imaging and often requires hysteroscopy with biopsy. According to Dr Tsakos, hysteroscopy combined with histology and microbiome testing remains the gold standard for assessing endometrial health.
Declining ovarian reserve is one of the most common reasons for secondary infertility. Dr Tsakos shared real clinical examples where women conceived naturally years earlier but later developed premature ovarian insufficiency, resulting in very low AMH levels and poor egg quality.
On the other end of the spectrum, polycystic ovarian syndrome can also contribute to secondary infertility, particularly if ovulation is irregular or poorly managed.
Hormonal imbalances, including thyroid disease, are frequently missed. Dr Tsakos noted that thyroid disorders can affect up to 20% of fertility patients and cannot always be diagnosed by TSH alone. Antibody testing is often necessary.
Endometriosis is a condition Dr Tsakos described as both common and frequently underdiagnosed. It affects around 10% of the general population and up to 50% of women with infertility.
Even women without classic symptoms may have endometriosis. Infertility itself can be the only sign. Dr Tsakos explained that with modern imaging and careful assessment, subtle signs of endometriosis or adenomyosis can often be identified.
Male factor infertility plays a role in up to half of infertility cases, either alone or in combination with female factors. Dr Tsakos acknowledged that male fertility has historically been underestimated, partly because ICSI was thought to bypass most sperm-related issues.
However, poor sperm DNA quality, oxidative stress, and high DNA fragmentation can negatively affect embryo development and pregnancy outcomes, even with ICSI. This is why advanced male testing, including DNA fragmentation analysis, is now an essential part of fertility assessment.
Lifestyle factors were described as critically important. Smoking, poor diet, obesity, stress, lack of sleep, and environmental exposures can all impair fertility in both men and women.
Dr Tsakos emphasised that small lifestyle changes can make a meaningful difference, especially in cases of mild to moderate infertility. Improving overall health is always the first goal, not IVF. Many couples achieve a natural pregnancy after relatively simple interventions, such as lifestyle optimisation, counselling, supplements, and cycle tracking.
Secondary infertility requires a systematic evaluation of both partners. According to Dr Tsakos, this should include:
– detailed medical and reproductive history
– full hormonal profiling
– advanced ultrasound assessment
– tubal evaluation when indicated
– hysteroscopy and endometrial testing where appropriate
– comprehensive male assessment, including DNA fragmentation
Many of these tests are non-invasive and can identify the majority of underlying causes when performed thoroughly.
Treatment depends on identifying and addressing the underlying cause. Options may include lifestyle changes, medical treatment, surgical correction, timed intercourse, or assisted reproductive technologies such as IVF.
Dr Tsakos highlighted that IVF, including PGT-A or donor options, may be appropriate in some cases, especially when age is a significant factor. Interestingly, he noted that couples with secondary infertility are often more open to donor options, driven by their strong desire to provide a sibling for their child.
Prognosis depends on age, duration of infertility, underlying causes, and how early intervention begins. With appropriate management, most couples have a good chance of achieving another pregnancy.
Dr Tsakos concluded by stressing that secondary infertility is common, often underestimated, and highly treatable. Many couples delay seeking help, losing valuable time.
Secondary infertility deserves the same attention as primary infertility. With early assessment, thorough investigation, and personalised care, most patients can achieve their goal of expanding their family.
Four miscarriages indicate that, by definition, there is a mild to moderate underlying fertility factor present. This is an important point.
Another factor is sperm DNA fragmentation at 21%, which is on the higher side, particularly if the male partner is over 40. Proceeding with hysteroscopic laparoscopy for suspected endometriosis or adenomyosis is appropriate, as these conditions are often diagnosed in women in their forties.
Given your age and reproductive history, the highest chance of pregnancy would likely come from IVF, ideally with ICSI and PGT-A. At 40, one might expect to retrieve four to five eggs, potentially resulting in one chromosomally normal blastocyst. Transferring such an embryo with appropriate support could give success rates closer to those seen in younger women. From a clinical perspective, this is the quickest route to pregnancy, although practical considerations such as cost and access must also be taken into account.
An AMH of 0.47 is very low for a 38-year-old, although collecting four follicles is still a positive sign. Empty follicles can happen and may be due to cycle timing or other unpredictable factors.
I would recommend baseline testing, including hormonal evaluation, basic genetic testing such as karyotype and cystic fibrosis screening, and male factor testing. Vitamin D levels should be optimised, ideally above 50. A healthy lifestyle, prenatal vitamins, and possibly DHEA supplementation may help improve ovarian response.
Careful monitoring of stimulation is essential. In some cases, daily or even twice-daily monitoring close to the trigger is required to ensure optimal timing. Adjusting stimulation dose or protocol may also be helpful. Given your history of natural conception, it is reasonable to continue IVF with close optimisation.
It is difficult to draw firm conclusions from immune testing alone, and strong scientific evidence for lymphocyte immunotherapy is limited. In my practice, I do not routinely offer it.
At the age of 40, the key question is which approach offers the highest and fastest chance of pregnancy. In my opinion, IVF with PGT-A provides the most direct and evidence-based route.
This should not be ignored. Thrombophilia can be congenital or acquired, and thrombotic risk may change over time and with factors such as estrogen treatment, infection, obesity, or prolonged immobility.
I recommend a full thrombophilia work-up to assess individual risk. In my practice, I use low-molecular-weight heparin liberally in higher-risk cases. It is relatively inexpensive, has minimal side effects, and offers both anti-thrombotic and anti-inflammatory benefits. With appropriate prevention, thrombosis risk can be significantly reduced.
My standard male assessment includes semen analysis, culture, DNA fragmentation testing, general biochemistry, hormonal tests, vitamin D, lipid profile, karyotype, cystic fibrosis screening, and thalassaemia testing.
Any identified abnormalities should be optimised before treatment. Generally, donor-egg cycles are not significantly compromised by moderate male factor issues. The key indicator of male contribution is blastocyst development rate and quality.
At 43, miscarriages are most commonly chromosomal. A previous pregnancy 16 years ago does not reliably reflect current fertility. Both partners should be thoroughly investigated.
Time is a critical factor, and IVF with PGT-A should be strongly considered to reduce miscarriage risk by ensuring chromosomally normal embryos.
Absolutely. Andrology should work alongside embryology within IVF units. Male fertility has a significant impact on outcomes, and specialised laboratories with trained andrology experts are essential.
Sperm quality reflects overall male health, and a comprehensive assessment benefits both fertility treatment and general well-being.
Preventive measures include avoiding unnecessary obstetric interventions and addressing complications promptly. Importantly, long intervals between pregnancies should be avoided where possible, as age has a significant impact on fertility.
In our clinic, we use a one-step fertility assessment: in one visit, we take a full clinical history, perform advanced ultrasound and tubal assessment, collect blood for hormonal and genetic testing, and assess semen parameters. This approach identifies around 90% of potential causes efficiently.
This happens more often than expected. Some individuals conceive despite underlying anatomical or male factors, essentially “winning with a losing hand.” Later, fertility may decline when circumstances change.
A key clinical question is how long it took to conceive the first child. Difficulty at that stage often predicts future challenges.
Patients with secondary infertility are often highly motivated because they have experienced the joy of parenthood before. Unfortunately, many delay seeking help, and by the time they do, age has become a major limiting factor.
Secondary infertility is common and deserves greater attention. Many couples could achieve pregnancy more easily if they sought assessment earlier. We are here to support them and provide solutions.
