Getting Pregnant with Premature Ovarian Failure

The word menopause refers to the last menstrual bleed. Menopause is clinically defined as amenorrhoea of 12 months' duration after the final menstrual period. Menopause does not usually occur until a woman has reached her late forties or early fifties. Symptoms of menopause include hot flushes, night sweats, sleep disturbance, depression and mood disturbance, memory and attention deficits, vaginal dryness, frequent urinary tract and Joint pain. For most women the symptoms spontaneously resolve within a few years (1-2 years). However, about one third of postmenopausal women will experience symptoms for longer periods and in about 10% women the symptoms are severe enough to warrant medical help. There are certain long-term health issues. Resulting from estrogen deficiency, these health issues primarily consist of an increased risk of cardiovascular disease and osteoporosis, which increases the risk of bone fractures.

What is Premature Ovarian Failure (Premature menopause)?

The term premature menopause (premature ovarian failure) is defined as the occurrence of menopause before the age 45. Premature ovarian failure can present at varying ages and in many forms. If premature menopause happens before puberty, the woman will present with lack of sexual developments and her periods will not started. If the condition presents after puberty, the woman will suffer from amenorrhoea and infertility. The diagnosis of premature menopause can be a shattering experience to the women and her family.

Since the woman's estrogen production is low, hormone replacement treatment is prescribed to put the brakes on the premature ageing effects of menopause such as hot flushes, night sweats, vaginal dryness, low mood and depression and osteoporosis. 

Premature Ovarian Failure, Early Menopause and Pregnancy

Pahlajani Test Tube Baby Centre is a leading fertility center in India with extensive experience in premature ovarian failure treatment for women who want to get pregnant with POF. With POF, correct diagnosis (distinction from premature ovarian aging) and treatment decision with which each patient feels completely comfortable are the two main pillars of our treatment philosophy. 

What is Premature Ovarian Failure (POF)?

Women with Premature Ovarian Failure (POF) also known as Primary Ovarian Insufficiency (POI), is a loss of ovarian function before the age of 40. POF can affect women at various ages from teenage years to thirties. Women with POF are at a greater risk of a range of health issues, including osteoporosis, estrogen deficiency (hot flushes, vaginal dryness, etc.) and heart diseases. These POF-related issues can usually be managed well with hormonal replacement. However, in an infertility context, POF poses a challenge, as the loss of ovarian function means that the probability of pregnancy in women with POF is greatly reduced.

Although it is sometimes called early menopause, POF is different from menopause in that POF is not a result of natural (normal) aging process of a woman. Women with POF, in addition, may continue to have menstrual cycles, though their cycles will be irregular. A small percentage of women with POF can conceive naturally, while menopausal women will never get pregnant.

Diagnosis of Premature Ovarian Failure (POF)

Even if you have been told that you have POF, it may be too soon to despair. Quite often, we are surprised who is diagnosed with POF. Many patients with a supposed diagnosis of POF actually don't really suffer from POF. Many "POF" patients, when tested at our clinic, turn out to suffer from premature ovarian aging (POA), not POF.

While these two conditions sound similar, correct distinction between POF and POA is crucial. Women with POA can get pregnant: CHR physicians have demonstrated, and reported in the medical literature, remarkably good pregnancy results in women with even severe POA (with DHEA supplementation and proactive ovarian stimulation). For women with true POF, chances of pregnancy with their own eggs remain, however, unfortunately quite small. Pregnancy attempts in POF, therefore, always involve experimental treatments, as no effective treatment has so far been established for POF patients.

·         The diagnosis of POF or POI is made with FSH hormone blood testing, often supplemented with AMH levels and ovarian antral follicle counts.

·         An FSH level above about 30-40 indicates ovarian insufficiency.

·         The serum AMH level is low

·         The antral follicle counts are very low

Symptoms of Premature Ovarian Failure

·         Periods becoming more irregular and farther apart

·         Hot flashes

·         Night sweats

·         Thinning and drying of the vagina

Incidence of premature menopause

About 1-3% of women will experience menopause before the age 40 years and 5% before the age of 45 years. The incidence of premature ovarian failure or the early menopause is on the increase. Premature ovarian failure accounts for about 10% of amenorrhoea and 1% of all cases of infertility.

What are the causes of premature menopause?

In the majority of cases no cause can be found. However, tobacco use, null parity, and family history are associated with earlier menopause. Some of the known causes include:

·         Congenital, if the ovaries failed to develop and are absent from birth.

·         Chromosomal abnormalities, such as Turner's syndrome, where the ovaries contain only a few follicles.

·         Genetic (Fragile X premutation). Some women's ovaries run out of eggs long before their middle age. This is possibly due to an increased rate of disappearance of follicles. The incidence of familial premature ovarian failure (POF) varies from 4% to 30%. The risk of a female relative developing POF may be as high as 100% in familial POF and as low as 1% in sporadic cases. 

·         Autoimmune disease. Thyroid disease and Addison disease are common in women with premature ovarian failure. Ovarian antibodies act against the ovaries.

·         The ovaries are physically damaged by infections, such as the mumps, or by cancer treatment, such as radiotherapy or chemotherapy. This later group is increasing in number because of the longer survival of cancer patients due to advances in both diagnostic modalities and treatment available.

·         The ovaries were surgically removed because of cancer or other causes.

What fertility options are available for women with PMM?

At present, the only realistic chance of a pregnancy for women with premature menopause lies through egg donation.

·         Many fertility centers are now offering ovarian tissue freezing and storage for women with a positive family history of premature menopause. The aim is restoration of ovarian function through the transplantation of ovarian tissue. Although the technique of transplantation remains experimental, successful transplantations has been reported that ovarian function was restored within 120 days. Furthermore, they reported six pregnancies. Some centre described freezing of a whole ovary from six women (age 26-35 years) prior to cancer treatment.  After a storage period of between 17 and 32 months, ovarian transplantation was performed. In all cases, the transplanted tissue restored menstrual cycles within 20 weeks of the transplantation. Four of the six women conceived following assisted reproduction: two of the women delivered a single healthy child one woman miscarried.

·         Egg freezing and storage is another option for women with a positive family history of premature menopause and has no partner. Many IVF centers are currently offering egg freezing. Technological improvements in egg vitrification offer young healthy women the possibility of preserving eggs until the less fertile years of life. The best age for egg vitrification is probably under 30 years. However, unrealistic reliance on the store of vitrified eggs may lead some women to defer pregnancy for many years only to experience disappointment when the stored eggs later fail to fertilize or implant.

·         IVF with donated eggs and nuclear transfer is another possible future treatment. Here the nucleus of a healthy donor egg is replaced with the nucleus taken from a skin cell that 'would be a mother'. The donor egg is then fertilized by the male partner’s sperm and the resulting embryo is subsequently transferred into the recipient.

·         Embryo donation is another option if the male partner is also infertile.

Getting Pregnant with Premature Ovarian Failure

As already noted above, even in the best of hands, pregnancy in women with POF is a rare event, and most will end up having to use egg donation. Our clinic does offer experimental treatments to POF patients, but we usually recommend donor eggs as the treatment of choice. However, at our clinic, it is always the patient who decides which way she wishes to go.

Most POA patients, in contrast, will have an excellent pregnancy chance with use of their own eggs at Pahlajani Test Tube Baby Centre. Our center has gained a world-wide reputation for treating women with premature ovarian aging, and our center's widely published pregnancy rates, even in women with very severely diminished ovarian reserve, have resulted in an ever increasing number of POA patients, from all over the world, seeking treatment at our clinic. Our success in treating POA patients is primarily based on the introduction of DHEA supplementation into fertility treatment. Indeed, today seven years later DHEA is used worldwide; but DHEA, alone, is only part of comprehensive treatment approach to POA. For example, if a POA patient were to receive the wrong DHEA or was treated for an inappropriate length of time and, especially, if ovarian stimulation is not adjusted to the POA patient's needs, DHEA effects will be disappointing. In other words, DHEA alone has only limited effectiveness, but within a comprehensive treatment paradigm, it has truly revolutionized the treatment of women with diminished ovarian reserve.

Unfortunately, DHEA appears much less effective and maybe even not effective at all, in patients with outright POF. Very low pregnancy rates in our past DHEA study in POF patients showed us that pregnancy chances in POF patients would, at best, be affected by DHEA only in a much more limited way, in comparison to POA patients.

Premature Ovarian Failure and Pregnancy through Egg Donation

In our opinion, nobody should enter an egg donation cycle without being absolutely convinced that it is their only realistic chance of having a child. We, therefore, not only respect our patients' desire to "at least try once" with their own eggs, but actually encourage such attempts if patients still believe they have what looks to them like a reasonable chance. Definition of "reasonable," of course, varies between patients, and what one patient considers reasonable may be too low for somebody else. We do not feel that we can make these judgments for our patients. We, instead, see our responsibility in making certain that our patients have accurate and comprehensive information when making these decisions. Only the patients can decide what represents a "reasonable" chance for them! Once they decide, Pahlajani Test Tube Baby will do its best to maximize pregnancy chances, whatever treatment patients choose. Egg donation is, undoubtedly, the most successful treatment option for women with POF. With their own eggs, POF patients have a pregnancy chance, at most, in the low single digits. In our egg donor program, the same POF patient will have a cumulative pregnancy rate in the high 80s to low 90s, from a single egg donation cycle. Since about 95% of an embryo's quality derives from the egg, and egg donors are typically young, recipients of donated eggs will have the pregnancy chances and miscarriage risks of a young woman. Imagine if we could do this in other areas of medicine!