Empty Follicle Syndrome

The empty follicle, or not getting any eggs on an egg collection is one of the most distressing things that tends to happen.  Does empty follicle syndrome occur, the answer is yes.

There are three types of empty follicle syndrome;

In a case presented in Human Reproduction they evaluated a woman who underwent nine cycles of IVF with HCG trigger. In the eighth cycle there were no eggs, in the ninth cycle an analogue trigger was given 40 hours before and a double trigger was done, and 16 eggs were obtained after eight cycles of IVF, thus signifying that sometimes changing the trigger significantly changes the outcome of pregnancy.

Folic Acid & IVF

Studies among sub-fertile women suggest a variable outcome in women taking foliate supplementation on ART outcomes.

In small randomised control trials women who took folic acid 0.4 mg had 16 per cent higher probability of pregnancy compared to placebo. In addition, two studies, the MTHFR mutation (low MTHFR allele activity and low serum foliate levels) was associated with poor ovarian response, fewer oocytes and lower gonadotrope cell production. An ART study in Boston, the EARTH study, showed that consuming more than 0.8 mg foliate compared to consuming less than 0.4 of foliate before conception had a higher rate of pregnancy. This has also been challenged by other studies which show in three European studies that it did not show a benefit, but this study may be challenged that certain patients were excluded.

In summary we could say that folic acid supplementation before and during pregnancy is not associated with the risks of miscarriage, but may still improve the chances of women achieving and maintaining pregnancy.

The Effectiveness of Aspirin in Women Undergoing IVF

In a study done in Human Reproduction in 2011, this question was answered to a meta analysis, is aspirin effective in women undergoing in vitro fertilisation? Aspirin has often been given to women undergoing IVF with the hope that it improves blood flow of the endometrium and allows the embryo to implant.

In the study ten studies were looked at in which aspirin was given and it confirmed that it did not improve blood flow in IVF patients and it did not improve pregnancy rates. There is some evidence that aspirin prevented the occurrence of preeclampsia during pregnancy, though the evidence is small. It is concluded that aspirin does not improve pregnancy rates in IVF and its routine prescription in IVF cycles is not good.

When Is The Right Time to Trigger With Clomiphene?

It is common practice to trigger ovulation at 18 mm size follicle.  Surprisingly all this has been standardised, and all the evidence which has been obtained has been obtained on the basis of studies done in the 1980s and 1990s, however many of the studies were done on those of IVF rather than on Clomiphene or Letrozole.

In an analysis of 988 cycles published in Fertility and Sterility, in a retrospective analysis they looked at the best time to trigger ovulation, rather than triggering at 18 mm; triggering at 22 and 23 mm seemed to give the best chance of success as well as improving the endometrial lining. By waiting for the follicles to grow larger, the endometrial thickness varied and improved, thus it may be important to wait and trigger ovulation around a slightly later time so as to improve the chances of pregnancy.

Fresh or Frozen Embryo Transfer

We are often asked which is best; fresh or frozen embryo transfer.  At Fertility Plus, we often favour frozen embryo transfers as this allows us to manage the timing better, but let’s understand a bit more about the evidence behind fresh and frozen transfers.

A large study published in a New England Journal of Medicine in January 2018 using women in China who did not have polycystic ovaries in their first IVF cycle between 20 and 35, had a stimulation and were given an HCG trigger. Of these women, 1077 had a frozen transfer and 1080 had a fresh transfer, results showed no difference between the live birth rates between fresh (50%) and frozen transfer (49%).  The first trimester loss (miscarriage) was similar, though in a frozen cycle the second trimester loss was significantly lower at 1.5 per cent compared to 4.5 per cent fresh embryo transfer.

Whilst showing no significant difference between fresh and frozen in the case of women without polycystic ovaries, in the cases of polycystic ovaries freezing of embryos would significantly improve pregnancy rates.

The advantage of a frozen cycle is whereby the acute stage of hormonal treatments are phased out and embryo transfer is done at a much better time when the ovaries do not have to work extra, hence at Fertility Plus we generally favour frozen embryo transfer.

Declining Sperm Counts in the Western World

Sensationalist media sometimes even call it ‘the end of civilisation’ which is nothing more than scaremongering, but the question does remain …. “have sperm counts declined?”

This question has been a controversial question, and the first time it was mentioned was in 1992, where it was suggested that there is a genuine decline in sperm quality over the past 50 years. This controversy has progressed unabated and has never been answered due to the lack of proper studies which have been conducted.


Why do we need to know the reason?

The reason why it’s important is that sperm counts are linked to male fertility, and semen analysis may be the only accepted way of assessing, or rather being the first stance of assessing male infertility. There are reports that suggested the economic burden that male infertility gives. It is also known that these sperm counts are the cause of male infertility and also the cause of multiple environmental factors such as endocrine disrupting chemicals, pesticides, heat, lifestyle factors, diet, stress, smoking, body mass index, all may be responsible for a decline in sperm counts.

In one of the largest systematic reviews done, published in Human Reproduction Update in November 2017, a team looked at 2510 full articles and looked at a huge number of studies between 1973 and 2011. This statistical evaluation reported a significant decline in sperm counts between 1973 and 2011, driven by a 50 to 60 per cent decline among men unselected by fertility from northern Europe to America, Europe, Australia and New Zealand. The research also indicated that there is no evidence of levelling off which means of slowing down of that declining trend.


What is the cause of the decline in sperm counts?

The causes which could be environmental or lifestyle in early childhood as well as in adult life, the endocrine disruption that comes in men from chemical exposures or maternal smoking during the critical times of male reproductive development, the exposure to pesticides that may have a role in adult life. The worrying factor is that we don’t know. At present, research is inadequate, but it is concerning that sperm counts are declining. A more robust long-term study is needed, and while this is on, it may be time to improve on how men look at health.

If you are considering starting a family it is worth the male partner doing the following:

If any medications are being taken they should be reviewed with a doctor.

Endometrial Scratch and IVF Success Rates

As part of a patient’s treatment sometimes additional fertility procedures can be recommended; endometrial scratch is fertility procedure that we can recommend in certain cases, especially where there have been failed cycles.  In this article, I explain endometrial scratch and the evidence supporting it.


What is Endometrial Scratch

Endometrial scratch is an additional fertility procedure where the endometrium (lining) is disturbed prior to an IVF cycle. This helps the embryo implant in the womb which is an essential part of fertilisation.


How Does Endometrial Scratch Work?

Before IVF, the womb lining is scratched with a small sterile plastic tube, which triggers the body to repair, releasing chemicals and hormones that make the womb lining more receptive to an embryo implanting.


What are the Success Rates?

There is reasonably good evidence that suggests that by doing an endometrial scratch prior to an IVF cycle or prior to embryo replacement success rates may be improved.  This evidence now comes from previous two or more failed cycles where this intervention could be helpful.


Are there any risks associated with Endometrial Scratch?

There are no risks associated with endometrial scratch, so it is considered a safe procedure.


Endometrial Scratch and IUI

Endometrial scratch is still relatively new and we are unaware whether there may be an improvement in pregnancy rates if it is done before an intrauterine insemination cycle.

In one of the largest studies which was published in Fertility and Sterility in 2017, an analysis was done of 23 studies of a total of 1871 cycles in which the endometrial scratch was done in the cycle prior. The evidence suggested that a scratch may improve the chances of a pregnancy in an intrauterine insemination cycle.

Though doing this may seem better, its evidence is not as good as that in IVF. The studies also concluded that the evidence was not as robust as performed in the IVF studies, and thus this should be taken more cautiously.

The HFEA regard endometrial scratch as a procedure which consistently shows benefit however further evidence is needed and as such there is a large clinical trial underway in the UK called the Endometrial Scratch Trial.

The Enigma of Endometriosis and Fertility

Is oocyte quality affected by endometriosis?

Endometriosis is one of the most common diseases found in reproductive women, with a significant impact on quality of life as well as fertility. For a long time, we are not entirely certain if oocyte quality is affected by endometriosis. In one of the reviews of literature published in 2017 in the general ovarian research, the effect of endometriosis was discussed. It is known that endometriosis causes distortion of the pelvis and also may release inflammatory markers (cytokines). It’s also known that it may impair endometrial receptivity.

The impact of endometriosis could be on mitochondrial content (the battery of the cell), show granulation, which is the breakdown of cytoplasm, measure spindle abnormalities in the cell and also may harden the zona, the outer shell of the cell. It is known that women with endometriosis have an imbalance in oestrogen, seen in IVF. They have lower levels of oestrogen during the IVF cycle, and it seems that the progesterone requirements are also altered in an IVF cycle.


Endometriosis and markers of egg quality

It is known that in women with endometriosis the eggs obtained have a hardening of the outer shell. There seem to be more immature than mature eggs, and also the spindle which is required to maintain the apparatus of the oocyte also seems to be altered in some cases of endometriosis. Mitochondria which are the batteries of the cell seem to be lower in endometriosis. In simple terms, is oocyte quality in endometriosis affected? Yes, there is a seven per cent more reduction in fertilisation, we get fewer eggs, fewer oocytes and less fertilisation.


Can we change oocyte quality?

The answer is no. Surgical intervention seems to have a negative impact on the ovary. Three to six months of long down regulation was suggested to improve pregnancy rates, but this has not been proved. There is some evidence that ICSI, rather than IVF, must be done to improve chances of fertilisation.
































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