Endometriosis, a painful condition in which the lining of the womb grows outside of it, robs many women of their capacity to conceive children.
Overseas studies show as many as four in 10 who seek help for infertility will have it.
And now, a study by the National University Hospital (NUH) suggests that women who have ovarian cysts because of endometriosis have a lower supply of eggs than women with other kinds of ovarian cysts.
Not only that, an operation which is commonly performed to remove endometriotic cysts can compound the problem by reducing the "ovarian reserve" of these women even more.
Having had the debilitating pain taken care of, women with endometriosis could continue to be frustrated by its effects long afterwards. It was a "surprising finding", said Dr Fong Yoke Fai, senior consultant and head of the division of benign gynaecology at NUH. It underscores the importance of diagnosing the condition before it progresses to causing cysts, at which point surgery may be unavoidable.
The study of 40 women, aged 21 to 40, measured concentrations of a hormone called the anti-Mullerian hormone (AMH) before and after surgery to remove ovarian cysts.
This hormone is produced by cells in women's ovaries to control the development of follicles in the ovaries from which eggs develop, making it a suitable marker of women's ovarian reserve.
In the NUH study, the ovarian cysts in 23 women were caused by endometriosis, with the rest stemming from other causes.
Dr Anupriya Agarwal, a consultant at the department of obstetrics and gynaecology at NUH, said the endometriotic cyst group started out with a mean AMH level of 23.9 picomoles per litre (pmol/L), compared with 33.7pmol/L for the other group.
An ovarian reserve of at least 6.5pmol/L is considered normal, while a level 19.8pmol/L and above is considered good. But a week after surgery to remove the endometriotic cysts, the women's average AMH level fell to 15.6pmol/L, which is below the "good" level.
Six weeks later, it inched up only to 16.2pmol/L.
In contrast, the other group of women maintained their ovarian reserve in the "good" range at both points of time, at about 27pmol/L.
Dr Agarwal said any type of surgery injures the ovaries. This, in turn, affects hormone levels. The slight rise for the endometriosis group may be due to ovarian tissues regenerating, although they would "never return to the baseline level".
Given that there is no screening tool for endometriosis, the most telling sign of the problem is menstrual pain, said Dr Fong.
His team is on a drive to educate primary care doctors to be on the lookout for endometriosis, which affects about 10 per cent of women.
NUH held its second forum for general practitioners last Saturday and its specialists will visit seven National Healthcare Group polyclinics this year to speak to doctors there.
Perhaps women can be spared the experience of Sandy (not her real name), who endured the pain for years, taking at least a day's leave from school or work each month - just to stay home doubled up in pain.
Doctors would give her painkillers and the 32-year-old engineer thought she was just "unlucky".
When Sandy failed to conceive a year after she got married, she went for a check-up at NUH and learnt that the source of her misery was endometriosis. She underwent surgery to remove four ovarian cysts but it was too late to help her.
A year later, she was still childless. Dr Fong encouraged her to try assisted reproduction methods. After three cycles of treatment, she finally gave birth to a boy last December.
Sandy had no idea that the condition could affect her fertility.
"It was coincidental that the doctor picked it up. Otherwise, I don't know for how long I would still be trying for a baby," she said.
CAUSE OF ENDOMETRIOSIS
The exact cause of endometriosis is not known, but one of the more popular theories is that some back flow of menstrual blood lands on and implants in abnormal sites in the pelvic region, such as the ovaries.
Dr Peter Chew, a senior consultant obstetrician and gynaecologist at Gleneagles Hospital, said most women have some retrograde menstrual flow, though not all have endometriosis.
It is believed that factors such as one's genes, the presence of environmental or man-made toxins, a weakened immune system and delayed childbirth increase one's risk of developing endometriosis, he said.
Endometriotic lesions release chemicals that cause pain and inflammation in the body, which then create a hostile environment for the egg, sperm or embryo (fertilised egg) to thrive for pregnancy.
Dr Steven Teo, a consultant at the department of reproductive medicine at KK Women's and Children's Hospital (KKH), said inactive lesions may also result in permanent scarring and distort the anatomy of organs, making pregnancy difficult.
An earlier study done in Taiwan that was published in the journal Reproductive Biology And Endocrinology in 2011 also showed that both ovarian cysts and the cystectomy procedure (ovarian cyst removal) are associated with a significant reduction in women's ovarian reserves.
The findings of the NUH study have prompted a follow-up study on how surgical techniques may protect a patient's ovarian reserve. For instance, whether bleeding can be stemmed using non-electrical means and if the surgical approach can be gentler, said Dr Agarwal.
CHALLENGES OF SURGERY
There is no cure for endometriosis, but it can be treated with pain medication or hormonal therapy.
Surgery is called for when the patient's symptoms cannot be relieved with medicine and are debilitating, when the cyst is so big that it may rupture or when there is a fertility problem.
Dr Yu Su Ling, senior consultant at the department of obstetrics and gynaecology at the Singapore General Hospital (SGH), called it a "fine balancing act" to remove as much abnormal tissue as possible to reduce the risk of recurrence, while keeping normal ovarian tissue intact.
Identifying and prising a cyst caused by endometriosis from the rest of the ovary can be challenging. Due to sticky scar tissue, it is more firmly stuck than other types of cysts.
Cysts in the ovary can be removed using manual or robotic methods.
Dr Anthony Siow, medical director of minimally invasive surgery at Parkway Gynaecology Screening & Treatment Centre at Gleneagles Hospital and a visiting laparoscopic trainer at KKH and SGH, said doctors first drain the cyst of blood before peeling it off the ovary. Surgery is considered a success when the cyst wall comes off in one piece with minimal bleeding spots.
To stop the bleeding that results, doctors use diathermy, which is the deep heating of tissues with a high frequency electrical current. But that can injure healthy ovarian tissues.
Dr Siow said he teaches trainees to scratch off about 30 per cent of the edges of a cyst - much like scratching a price tag off with one's fingernails - before peeling the whole cyst off cleanly. A cyst which comes off in strips will lead to more bleeding and results in more burning and damage to ovarian reserve, he said.
Dr Loh Seong Feei, medical director of Thomson Fertility Centre, said it is crucial that surgeons "be taught to respect ovarian tissues".
He said they should be meticulous during surgery and stop bleeding at its source, instead of burning the ovary indiscriminately.
Doctors say the magnified view offered by laparoscopy is why it is commonly used for endometriosis surgery. Four hospitals- NUH, SGH, KKH and Mount Elizabeth Hospital - now also offer robot-assisted surgery for severe endometriosis, though at least one doctor, Dr Loh from Thomson Medical, feels that robotic arms cannot replace the tactile sensation in the human fingers.
Six doctors told Mind Your Body that the NUH study should not deter doctors and suitable patients from a cystectomy.
Dr Siow said AMH levels do not solely determine one's fertility, which also depends on factors such as whether the fallopian tubes are open as well as the quality of eggs and the sperm.
Dr Teo said women are "very unlikely" to end up with no eggs after endometriosis surgery.
Those who started out with very few eggs and wish to conceive may first be offered in-vitro fertilisation to harvest their eggs before having their endometriosis treated through surgery.
Get a copy of Mind Your Body, The Straits Times or go to straitstimes.com for more stories.