Preparing for a baby — for women

Having a baby does not rest on the woman alone — but there really are a good many things a woman should know before she starts trying. This page gathers all fifteen of my articles on getting the woman ready. Read them straight through, or jump to whichever one fits you.

• Age and fertility
• Śakti supplement
• Prebiotics
• Ovarian rejuvenation
• Tubal patency test
• A normal period
• Ovulation timing
• The first hCG result
• PRP
• DHEA
• Diet and weight
• Probiotics
• NAC
• Bromelain
• CoQ10 and egg quality

Age and female fertility

I once surveyed people walking around the Suan Oi neighbourhood outside Vajira Hospital, to see how many knew that a woman's fertility falls with age. Only 20% had any inkling of it. The rest were rather in the dark — some of them thought a woman could get pregnant right through her life.

A woman's egg supply peaks at 20 weeks of gestation, while she is still inside her own mother — about two million. From then on it only falls. By the day of her first period she has roughly two to four hundred thousand eggs left. After that, batches of eggs are woken up and put to work all the time, but in each cycle only one of them ripens and is released to wait for fertilisation.

It is not only the number that falls. The longer an egg has been in the body, the longer it has been exposed to environmental toxins, to genetic wear and to free radicals. Chromosomes get damaged, and the mitochondria — the power plant of the egg cell — start to misfire. The result is more chromosomally abnormal eggs, and embryos that divide poorly because there is not enough energy to divide well. That is why pregnancy rates fall and miscarriage rates rise with age.

On average this reproductive ageing begins at about 32, becomes clearly visible after 37, and after 45 the chance of conceiving is very small indeed. And it is not only the ovary. The uterus changes with age too — the muscle contracts less in concert, the lining receives an embryo less well than it used to, and there is more chronic inflammation inside the cavity.

As the forties approach, egg numbers have dropped a long way and hormone levels start to shift — and that reaches the rest of a woman's health as well:

• Metabolism slows, so weight goes on very easily — on average half a kilogram a year even when you eat exactly as before.
• Body fat redistributes, collecting more in the abdomen — abdominal obesity.
• Insulin resistance sets in, which can raise blood sugar, disturb the lipids and cholesterol, and push blood pressure up.
• In the long run bone thins, and can reach osteoporosis — which costs height, rounds the back, and lets a bone break on even a light knock.
• Once hormones drop far enough, menopausal symptoms can appear — hot flushes, sweating, poor sleep, dry skin, vaginal dryness. If they are bad enough to disturb daily life, they should be treated.

We cannot stop the birthdays, but some things can still be done. Women at risk of losing their eggs early — Turner syndrome, a Fragile X premutation, anyone facing chemotherapy, ovarian surgery or pelvic radiotherapy — may want to consider fertility preservation: freezing eggs, freezing embryos, or freezing ovarian tissue. And for a woman with no plans for a child now but who expects to want one later, egg freezing is one option. Live healthily; avoid alcohol, tobacco and recreational drugs. And let me say it plainly: no supplement and no treatment beats your age.

Full article: Age and female fertility

Śakti — a comprehensive supplement for women

Patients are forever asking me which supplement is worth taking when you are having trouble conceiving. The market is full of them — from the serious ones all the way down to half-belief and outright pseudoscience. So I put together a formula of my own, Śakti, so that a patient can take it once a day and get the lot: one capsule, once daily, before food. I built the formula out of the research, went to see a GMP-standard factory, registered it with the Thai FDA, chose the packaging myself and designed the label myself. Every one of those steps is so that the patient can be confident she is getting the full benefit, safely, and without paying through the nose.

In the article I lay the research out nutrient by nutrient, so you can see what each ingredient is doing there:

• Coenzyme Q10 — a fat-soluble antioxidant that protects DNA from oxidation and helps the cell make energy efficiently. After 8–12 weeks of use it was found to raise the pregnancy rate significantly, to give more mature eggs, a higher fertilisation rate and more good-quality embryos, both in women with low ovarian reserve and in women with PCOS.
• Vitamin C — a water-soluble antioxidant. Women taking vitamin C during an IVF cycle had a significantly higher pregnancy rate than those who did not.
• Vitamin D — fat-soluble, involved in bone and muscle, and it also bears on the reproductive system in both sexes. Women with low blood vitamin D were found to have a lower chance of pregnancy from IVF than women with normal levels.
• Folic acid — a B vitamin that guards the baby against neural tube defects. Even though studies in IVF patients found no relationship between blood folate and the pregnancy rate, it should still be taken, for the baby's sake.
• Vitamin B3 (niacinamide) — research has found it can slow the death of egg cells and help with early menopause.
• Zinc — a mineral that matters for normal egg-cell division, for fertilisation itself (at the moment of fertilisation there is a flash of zinc, the so-called zinc spark), for normal embryo division, and on through to implantation.
• Vitamin E — antioxidant and anti-inflammatory. Research found that vitamin E improved egg and embryo quality: the embryos divide cleanly, with less fragmentation. And in endometrial preparation cycles, women given vitamin E had a thicker lining than those who were not.

Full article: Śakti — a comprehensive supplement for women

Prebiotics and female fertility

Prebiotics are substances the human gut cannot digest or absorb, so they reach the large bowel unchanged — where they become the food supply for the probiotics, the friendly bacteria living in the gut. They count as functional food. You find them in certain vegetables, fruits and grains: onion, garlic, soy bean, red bean, chicory root, artichoke, asparagus, banana and apple.

Probiotics, for their part, are live beneficial microorganisms which, taken in the right amount, support the working of the body's systems. Besides living in the gut and the vagina, they turn up in food: cultured milk, yoghurt, kimchi, pickled cucumber, miso and fermented tea. When prebiotics and probiotics work together, we call the pair synbiotics.

So what has this to do with having a baby? Studies have found that taking prebiotics and probiotics reduces inflammation and can restore normal ovulation, because:

• it normalises the working of the granulosa cells and lowers inflammation;
• it supports the growth of the follicle and the egg cell;
• and it keeps the hormonal and immune systems working normally.

Good health from the inside, in other words — and fertility follows along with it.

Full article: Prebiotics and female fertility

Ovarian rejuvenation — for low ovarian reserve or premature ovarian insufficiency

This one is specifically for patients with a low egg count — DOR, diminished ovarian reserve — or with premature ovarian insufficiency, POI. A review in Reproductive BioMedicine Online gathered together the three treatments that actually do something to rescue the ovary in these two groups. (And please don't ask me about supplements. If you have reached the point where stimulation yields one or two eggs, or none at all, you are well past where a supplement can help.)

1. In vitro activation (IVA)

The ovarian tissue is taken out by laparoscopy and worked on outside the body, to wake up the sleeping primordial follicles — either by cutting the tissue into small fragments, or by culturing it with certain drugs or agents such as a PTEN inhibitor. Then a second laparoscopy is needed to graft the tissue back onto the ovary. It is done in several countries, Japan among them, with reasonably satisfying results. The drawbacks are that it means going into the abdomen twice, and that the long-term effects of the drugs used in culture — on the patient herself and on any baby born afterwards — are not known. So it has not become popular.

2. Stem cell infusion

Here stem cells are used to restore the follicles. They may come from the patient's own bone marrow (BMDSC), from filtering her blood after she has been given a drug that stimulates blood-cell production (HSC), or from umbilical cord blood (UCMSC). They can be delivered through the artery that supplies the ovary, or injected straight into ovarian tissue. A great many studies have found more eggs, better hormone levels, and pregnancies do occur. The drawback: donor cells have to be cultured in a high-grade laboratory and tested thoroughly before they reach the patient, which makes them expensive — tens of thousands of baht per treatment — and the result may take three to four months to show.

3. Platelet-rich plasma (PRP)

Blood is taken from the patient herself, spun down to a high concentration of platelets, the platelets are activated, and the preparation is injected back into her ovary. This has been found to raise the antral follicle count, to give more eggs at retrieval, to improve the chance of pregnancy, and also to produce more chromosomally normal embryos. How long it takes to show depends on whether the problem is DOR or POI. With a low count (DOR) you may see something one to three months after treatment. Where the ovary has all but stopped (POI) it can take three to five months, because PRP has to wake the follicles right down at the sleeping stage, and those may need up to five months to grow to the point where ultrasound can see them at all — the antral stage. As things stand, I think PRP is the best value of the three.

You can see that in DOR and POI, getting the ovary to come back is genuinely hard work. So if you think you may be having trouble conceiving, come and get it looked at early, before time does any more damage than it already has.

Full article: Ovarian rejuvenation — for women with low ovarian reserve or premature ovarian ageing

Checking that the fallopian tubes are open (tubal patency test)

The fallopian tubes run straight off the uterus, one on each side, and they do several jobs in conceiving: they catch the egg as it leaves the ovary, they are the road the sperm travel, they are where fertilisation happens, they carry the embryo for its first four or five days after ovulation, and then they move it into the uterus to implant. You could say the fallopian tube is the incubator we use in the IVF lab — except it is the original.

When the tubes do not work — blocked tubes, hydrosalpinges, or inflammation — the opening moves of pregnancy simply cannot happen. That is tubal factor infertility, and it accounts for 15–30% of infertile couples. It also decides the treatment: abnormal tubes are a contraindication to intrauterine insemination (IUI), because there is nowhere suitable for sperm to meet egg. A woman with damaged tubes has to be treated with IVF or ICSI.

Assessing the tubes has a long history: hysterosalpingography (HSG) was first reported in 1895, and many methods have come along since — some gone, some still with us. The ones in common use now are:

• X-ray contrast study of the tubes (hysterosalpingography, HSG)
• Ultrasound assessment — hysterosalpingo-contrast sonography (HyCoSy)
• Foam-contrast ultrasound (hysterosalpingo-foam sonography, HyFoSy)
• MRI assessment (MR HSG) and virtual CT assessment (CT HSG)
• Laparoscopy with dye passed through the cervix (laparoscopic chromopertubation)

HSG was the first method reported. Low-dose X-ray is combined with contrast pushed through the cervix, so the shape of the uterine cavity and both tubes can be judged from how the contrast spills. There are two kinds of contrast — water-soluble (WSCM) and oil-soluble (OSCM) — and OSCM may even be therapeutic where a mucus plug is blocking the tube. Against HSG: it hurts and is uncomfortable, it puts radiation through the pelvis, and it is not very accurate — for proximal tubal occlusion in particular, HSG is right only about 40% of the time.

Laparoscopic chromopertubation — looking inside the abdomen with a laparoscope while dye is pushed through the cervix — is the gold standard, and it is highly accurate. But it is invasive: general anaesthesia, a breathing tube, and a stay in hospital. So we do it only when the patient needs a laparoscopy for something else anyway.

HyCoSy uses ultrasound while saline carrying tiny air bubbles is injected into the uterine cavity. You watch the bright bubbly saline come out of the fimbrial end of the tube and gather around a normal ovary — the ovarian rim sign. Its advantages: almost no pain, low cost, no hospital stay, and it can be done in nearly any fertility clinic, since the ultrasound is there already. Add 3D ultrasound (3D-TVUS) and you can show contrast leaving both tubes at once, just as HSG does. HyFoSy differs only in using a foam-textured contrast, which holds more bubbles than saline, so it shows up whiter and clearer. Both are very accurate — close to laparoscopic chromopertubation. As for MR HSG and CT HSG, I find them cumbersome, the machines are few, and they cost a great deal; they are not worth ordering.

In short: which method to choose depends on the experience and skill of the centre doing it, and on the patient's own situation.

Full article: Checking that the fallopian tubes are open (tubal patency test)

What counts as a normal menstrual cycle?

Did you know that inside one period there are actually two cycles running at once? There is the menstrual cycle — the cycle of the endometrium, which builds itself up and gets ready to receive an embryo. And there is the ovulatory cycle — the making of the egg and of the sex hormones, which go off to talk to the pituitary and to the hypothalamus, and to the uterus and the rest of the reproductive tract.

A normal period has four characteristics:

• Interval — from the first day of one period (the first day of bleeding) to the first day of the next is normally about 21 to 35 days.
• Duration — bleeding lasts about 3 to 7 days.
• Amount — one period loses about 80 ml of blood, roughly six tablespoons (nobody is going to sit there measuring it), or about four to five pads on a heavy day.
• Regularity — if your period comes every 21 days, it should be the same gap every month. Twenty-one days this time, then nothing for two months, then thirty days — that is not regular.

There are a great many things that can go wrong with periods. If something is not right, go and talk to a gynaecologist.

Full article: What counts as a normal menstrual cycle?

How to work out when you ovulate

A study going back to 1995 found that if you have intercourse only once in a cycle, the best chance of pregnancy falls on the two days before ovulation, the day before, and the day of ovulation itself. The day after ovulation the chance is zero. Why? Because sperm can live three to five days in the uterus and the tubes, while the egg, once released, lives only 12 to 24 hours. If no sperm arrives to fertilise her, she shrivels and is gone, and we start counting again next month.

So how do people track ovulation? Anyone who has been trying for a while has used at least one of these:

• marking the calendar (desk, wall, whichever);
• basal body temperature (wake up, do not get out of bed, measure first, write it down — every single day);
• watching the cervical mucus (clear and stringy — off you go);
• urine LH tests (every brand under the sun, from the five-baht strip to expensive gadgets that link to an app);
• smearing saliva on a slide and looking for fern-shaped crystals (see a fern, get on with it);
• and phone apps, on both the App Store and Play Store, now beyond counting.

Every one of my patients has heard me say: turn your attention to something else, and do not lie at home doing nothing after an embryo transfer. Stress is one of the biggest reasons a pregnancy does not happen. And ovulation tracking is exactly that — stressful.

Several studies have compared taking it easy — intercourse two or three times a week — against tracking ovulation and then going hard at it during the fertile week. The easy-going approach wins. Here are the numbers:

• every day through the cycle — 75% pregnant within 3 months;
• every other day through the cycle — 66% within 3 months;
• an easy two or three times a week — 60% within 3 months;
• and busy counting ovulation days — down to just 30–40% within 3 months.

So stop counting. If your cycle is regular — 24 to 35 days, not "regularly every three months" — then whenever you like is fine. Steady, two or three times a week: that is where the odds are best. Loving each other regularly is the best method there is.

Full article: How to work out when you ovulate

What does the first pregnancy-hormone test after embryo transfer tell us?

Lately a lot of patients have come to me after having their pregnancy hormone measured — human chorionic gonadotropin, hCG. Sometimes they have decided by themselves that the number looks too low; sometimes it is a member of the medical staff who tells them the level looks too low. Either way it leaves the patient, and her family, badly worried.

I would like everyone to take a breath first. In the article I go through this with diagrams — what that first result does and does not tell us. Do go and have a look.

Full article: What can a single pregnancy-hormone test tell us?

Few eggs, poor egg quality — and is PRP new hope for infertility?

Few eggs. Poor egg quality. Unattractive embryos, too few embryos, embryos with the wrong chromosome count, transfers that do not take. These can come from age, which does us no favours at all; from stimulation drugs that are not yet the right ones; or from the egg collection and the handling in the laboratory. Treatment has to start with whatever we can actually identify — and then there are the add-ons, of which there are three worth discussing.

DHEA

DHEA is a weak androgen normally made by the adrenal gland. Abroad it sits on the supplement shelf, and the dose for a woman is 25 mg a day — that is all. In small doses it can raise the number of antral follicles; research found it gave one or two more eggs at retrieval. (Do not sniff at a single egg: studies suggest each extra egg may add as much as 5% to the chance of pregnancy.) The drawbacks: it takes two to three months to show anything, and — this matters — even 25 mg may be too much for a Thai woman. At high doses DHEA and androgens do not give you better eggs; they drive egg cells to die.

Growth hormone (GH)

Growth hormone comes from the pituitary, mostly while we sleep, and it repairs the body's wear and tear. Production falls as we get older, so people have tried using it to raise the egg count. The effect is small — one or two more eggs. The drawbacks are substantial: a daily injection for a month, a high price (tens of thousands up to a low six figures in baht), and in Thailand only a paediatric endocrinologist may prescribe it. No other specialty can.

Platelet-rich plasma (PRP)

PRP is made from your own blood: it is drawn, spun in the lab until the platelets are two to three times as concentrated as in ordinary blood, and injected back into the ovary. Platelets are the body's first responders to injury; when activated they release a range of substances, in particular platelet-derived growth factor (PDGF), which has a real part to play in rejuvenating tissue. PRP has been used for decades in age-related conditions — knee osteoarthritis before a knee replacement, hair loss, even facial rejuvenation. An ageing ovary is an age-related condition too, so PRP might turn its clock back as well.

Research has found that injecting PRP into the ovary may raise the antral follicle count, raise AMH — the hormone that reflects how many eggs are left — increase the number of eggs retrieved, and improve embryo quality, all of which ought to improve the chance of pregnancy. It has been studied both in women who produced few eggs on a previous stimulation and in women with premature ovarian insufficiency. The patient numbers are not large, but the studies all point the same way, and since the cells are the patient's own it should be safe. PRP has also been put into the uterine cavity for a thin endometrium, for women whose transfers have repeatedly failed, and after surgery for intrauterine adhesions (Asherman syndrome) — with good results there too.

Full article: PRP — new hope for infertility?

Say "NO" to DHEA — please do not go and buy it, I am warning you

Honestly I did not much want to write this one — I will be treading on somebody's toes. But it has to be written, because patients keep asking, and I keep meeting women who are taking DHEA in the hope that it will give them more eggs. Let me say up front: there is still not much good-quality research here. Use your judgement.

DHEA is a weak androgen made by the adrenal gland. The reason anyone tried it is this: women with slightly raised androgens — those with PCOS, for instance — tend to have more follicles than usual. So someone thought to give DHEA to women with few eggs, hoping the count would go up. But if the androgen level goes too high, instead of more eggs you get the opposite: it drives the egg cells to die off.

So who might it suit? A woman aged 40 or over who is about to be stimulated, and a woman whose previous cycle gave an antral follicle count under five to seven. And starting it today will do nothing — it has to be taken for at least two to three months before stimulation to have any effect.

Here is what set me off: people are selling the 100 mg strength to women with fertility problems. That is far too much — the 100 mg is meant for men, for weight loss or a bit of vim. And a man with fertility problems must not take it either: his sperm will vanish entirely. It upsets me to see patients buying this in good faith. There is no benefit in it, only harm. Talk to a doctor before you start. Do not let someone take your money for nothing — money gone, heart broken, no eggs, and time wasted.

And one published study found that adding DHEA conferred no additional benefit over growth hormone alone, on either pregnancy rates or live birth rates, in IVF patients categorised as poor prognosis.

Full article: Say "NO" to DHEA

Diet and weight loss, and having trouble conceiving

If you are a patient of mine you have probably been told — or nagged — to go and exercise and lose some weight. There are broadly three camps of weight-loss diet.

1. The low-carb camp

Eat less starch and sugar. There are many versions — ketogenic, Atkins and so on — differing in how far they cut the carbohydrate. The idea is that less insulin is made, so the body draws more of its energy from fat and stores less surplus. It sounds good. The downside is that burning protein and fat leaves more waste — ketones, ammonia — which over the long run may not do your health any favours. And some low-sugar products have to use non-nutritive sweeteners to keep tasting the same, which people with certain genetic conditions cannot have.

2. The low-fat camp

Eat a smaller proportion of fat. This comes from what we know about heart attack and stroke: long-standing high cholesterol in the vessels, together with arteries that have lost their elasticity with age. These days the shelves are full of low-fat and fat-free products. What has happened, though, is that some of them turned to plant fats containing trans fat, which the body cannot use and which may block vessels more readily than animal fat does. And for patients of reproductive age, men and women both, let me say this plainly: you need cholesterol. It is the precursor of every sex hormone in your body — oestrogen, progesterone and testosterone alike.

3. The low-calorie camp

This one I think makes the most sense. Everything you eat, carbohydrate or fat, is energy, and the body balances itself. This camp is calorie counting in its various forms, including the apps that count for you and work out what your body needs; intermittent fasting sits roughly here too. Weight goes up because you eat more than your body needs and use less energy. So eat less and move more. Some people cut the food and skip the exercise — then the body decides it is starving, metabolism drops with it, and the weight will not shift.

Really, if you eat in moderation you can eat anything at all. Have what makes you happy.

Full article: Diet and weight loss

Probiotics and female fertility

Probiotics are bacteria that do the body good. They help balance the friendly and the unfriendly bacteria, both in the digestive tract and in the vagina.

Lactobacillus is the beneficial species found in abundance in the vagina. A balanced Lactobacillus population there helps keep infection away and holds the vaginal pH where it should be.

A healthy endometrium matters for pregnancy too, and Lactobacillus may help support it. Taking a probiotic containing Lactobacillus may encourage a richer lining, and with it a better chance of conceiving. I hope this is useful to women who are planning a pregnancy.

Full article: Probiotics and female fertility

Let's detox with NAC

N-Acetyl Cysteine (NAC) is an antioxidant. In medicine it is used to thin mucus, and as the antidote in paracetamol overdose. On the fertility side, there is research into using NAC as a supplement to help fertility — besides helping to detox a liver that has been working hard filtering every hormone thrown at it.

Full article: Let's detox with NAC

Bromelain — a new helper in the embryo transfer cycle

For those having trouble conceiving, miscarrying repeatedly, or whose embryo transfers have not worked: bromelain is an enzyme extracted from pineapple. Without a coating that survives stomach acid, all it does is aid digestion and settle bloating. But if it gets past the acid it is absorbed, and then it:

• reduces inflammation (anti-inflammatory);
• reduces blood clotting (anticoagulant) — and those first two are exactly what aspirin does, the aspirin patients are so often given around the time of transfer;
• reduces pain;
• and reduces the formation of adhesions, whether from disease such as endometriosis or after surgery.

Full article: Bromelain — a new helper for embryo transfer

CoQ10 and egg quality

Following on from what I have written before about antioxidant supplements for women: a study has just been published on what CoQ10 does to the quality of the cumulus cells, the nurse cells around the egg. It compared three groups — young mice, old mice, and old mice given CoQ10 at a dose already shown to treble the CoQ10 concentration in the ovary.

The results:

• the number of cumulus cells per egg was higher in the young mice and in the old mice given CoQ10 than in the old mice without it;
• degenerative cell death in the old mice given CoQ10 was as low as in the young mice, and lower than in the old mice without it (measured by caspase-3);
• DNA damage in the old mice given CoQ10 was close to that of the young mice, and less than in the old mice without it (by TUNEL);
• and cumulus cell function — judged by mitochondrial number, glucose uptake and progesterone production — was similar between the young mice and the old mice on CoQ10, and better in both than in the old mice without it.

In short: in mice, CoQ10 supplementation can slow the ageing of the cumulus cells. In humans, the data are as I have presented before — taking it is better than not taking it.

Full article: CoQ10 and egg quality

With my best wishes — Dr. Patsama