Friday, 26 June 2020

Vol.16, JUNE 2020, Recurrent IVF failure: What to Do

Recurrent IVF Failure - What to Do

Mr J. Adeghe PhD, FRCOG., Consultant – Fertility & Gynaecology

St Jude Hospitals & Clinics, UK.

1. Attend for review with your Specialist/Consultant and ask specific questions:

  • His or her opinion on possible cause for treatment failure
  • What further tests should be performed to identify any underlying problems
  • Was the endometrial thickness adequate during treatment cycles?
  • Was embryo development and quality satisfactory
  • Was Blastocyst culture performed?
  • Would he / she consider referring you for a second opinion

2.   Lifestyle changes – it is very important to correct any unfavourable lifestyle features that exist

·        Stop smoking

·        Give up alcohol consumption

·        Achieve BMI <30 through diet control and exercises

·        Adopt good dietary plan – based on the Mediterranean diet

·        Reduce Stress in your life – at home and at work

3. Investigations to Consider:

  • Blood test for Thyroid Function - TSH, Thyroxine, Thyroglobulin Antibodies, Thyroid Peroxidase antibodies
  • Full Blood Count - Haemoglobin level and other blood indices
  • Blood test for Vitamin D & Calcium levels
  • Infection screen for Chlamydia, Gonorrhoea, Mycoplasma genitalium, Ureaplasma genitalia, Trichomonas vaginalis, Gardnerella vaginalis, Herpes Simplex I/II
  • Pelvic Ultrasound scan

4. Other Specialist Investigations to Consider:

  • Blood test for Immunological factor - Checking for Natural killer (NK) Cell activity
  • Laparoscopy to exclude Hydrosalpinx which will require Salpingectomy
  • Hysteroscopy to exclude endometrial polyp and also to take a biopsy to check for underlying inflammatory pathology
  • Uterine artery doppler studies – Poor uterine blood flow may be related to suboptimal endometrial thickening
  • DNA fragmentation test on semen sample – if sperm quality is poor

5. Treatment strategy:

·        A review of previous treatment cycles and results of investigations will influence the choice of treatment protocol:

a) Long protocol

b) Short protocol with agonist

c) Short protocol with antagonist

d) Elective freeze of all embryos and subsequent frozen embryo replacement (FET)

·        Depending on findings from previous treatment cycles, AMH result, and sperm quality, it may better to consider:

a)      Donor eggs

b)      Donor sperm

c)      Surrogacy

d)      Decide that further IVF cycles are unlikely to be successful, therefore Adoption should be considered


Friday, 12 June 2020

Vol.15, JUNE 2020, Effectiveness of a structured Fertility Diagnosis Package

Effectivenesss of a Structured Fertility Diagnosis Package

Sarah Baker – Fertility Midwife, Jackie Loveridge – Senior Fertility Nurse,

Jude Adeghe – Consultant Gynaecologist, Rasiah Sriskandakumar – Senior Clinical Embryologist.

 

Introduction

Without reaching a diagnosis, appropriate treatment of subfertility cannot be rationally determined. Therefore, an effective plan of fertility investigations to establish a diagnosis is a sine qua non for the management of subfertility.

St Jude’s Clinic offers the One Stop Fertility Diagnosis Package to facilitate the TTC (Trying To Conceive) journey for couples. The essence of the package is to assess the keys pillars of fertility – Ovarian reserve / function, tubal patency and sperm quality.

 The package includes:

-         Blood tests for Anti-Müllerian Hormone (AMH) to check reserve of eggs in the ovaries

-         Blood test to check Rubella immunity

-         Pelvic Ultrasound Scan

-         High Vaginal Swab (HVS) to screen for infection

-         HyCoSy (Hysterosalpingo-contrast-Sonography) procedure to assess tubal patency

-         Semen analysis

-         Review by Consultant to discuss results and treatment options

Objectives

Our clinic has been offering this package of investigations for many years but no formal audit has been conducted so far. The reason for conducting this audit is to assess the effectiveness of the package in terms of the following:

·        Reaching a diagnosis  

·        Time taken to complete all tests within the package

·        The range of abnormalities identified by the tests

·        Any complications arising from HyCoSy procedure

·        What treatments those who took up the package went on to have and their relative success rates in conceiving

Data Collection

All women who had HyCoSy procedures at St Jude’s in 2019 were identified by reviewing the theatre record book. These notes were then pulled from file to assess which patients had the one stop package.

Data was collected on the following parameters:

-         Name

-         Patient ID number

-         Age

-         BMI

-         Duration of Infertility

-         AMH result

-         HVS result

-         Pelvic Ultrasound Result

-         HyCoSy findings

-         Semen analysis results

-         Subsequent Fertility Treatment

-         Treatment Outcome

-         Pregnancy Outcome

 

Data Analysis

Data was collated by category to summarise frequencies of different outcomes and calculate percentages for applicable parameters.

Mean values were calculated for patient characteristics to assess the demographic of women included in the audit and cross reference outcome data.

Results

A total of 41 women who took up the One stop Fertility Diagnosis Audit in 2019 were included in the audit. The mean age of the women included in the audit was 33 years (range 20 years – 46 years) and average BMI was 26.5 (range 19.4 – 48.5) . Mean AMH level was 18.0pmol/L (range 0.7 – 85.4pmol/L). 21% of AMH results were classed as low (<5pmol/L). This is an important discovery to best advice patients on the most effective treatment options and ensure they act sooner rather than later to prevent further decline in ovarian reserve.

41% of HVS results came back abnormal (17 out of 41), with results varying from Candida species, Bacterial Vaginosis Grade 2-3, Ureaplasma/mycoplasma and GBS. All abnormal swab results were treated with over the counter treatment or antibiotic cover. By doing so any abnormal flora or bacteria are removed and the chances of conceiving are improved. GPs were informed of GBS positive results for future reference in pregnancy.
As part of the HyCoSy procedure, broad spectrum antibiotics are routinely given intravenously with sedation medication (Cefuroxime 750mcg). Where abnormal HVS results are identified, HyCoSy procedures are postponed to enable adequate time for treatment to be effective.

17% of trans-vaginal Ultrasound Scans identified abnormalities in pelvic anatomy: most commonly Polycystic Appearance of the Ovaries; other abnormalities included the presence of simple ovarian cysts, multicystic ovaries, fibroids and in one case an arcuate uterus.

The vast majority of HyCoSy procedures concluded Bilateral Tubal Patency (85%), only one patient had Bilateral Tubal Blockage (2%). Five patients had one blocked tube and one patent tube (12%).

Semen parameters were normal in 54% of the men included in the audit. The remaining 46% had reduced parameters of some kind. Results varied from marginally reduced parameters in only one parameter, or increased WCC only, to multiple sperm abnormalities requiring ICSI treatment.  Azoospermia was recorded in one case.

50% of patients went on to have simple ovarian induction treatments with clomifene or letrozole tablets after the one stop package. 11% of patients proceeded to have IUDI treatment (all single women or same sex couples), 17% of couples had IVF/ICSI treatment after the one stop package, usually in cases where there was a tubal blockage or semen parameters were reduced.

The remaining 22% of patients had no treatment at all subsequent to the One Stop Diagnosis Package. Some of these women contacted clinic to inform us that they had conceived naturally, however many did not follow up at all, therefore it is unclear is these women conceived and therefore required no further input from St Jude’s or whether they decided not to pursue fertility treatment or to go to another clinic.

Results show that the percentage of patients included in the audit who conceived after taking up the One Stop Fertility Diagnosis Package was 34%. However a further 22% of women had no follow up. Of the 14 couples who conceived, four conceived with no treatment at all (29%), seven couples conceived following simple ovarian stimulation with clomifene or letrozole (all fewer than 4 cycles) (50%) and three couples conceived following IVF or ICSI treatment (maximum one fresh cycle) (21%).

Due to the timescale of the audit, some treatments are still ongoing therefore some outcome data is not yet available.

Discussion

Current guidelines support the use of the investigations included in the one stop fertility diagnosis package.

AMH is a widely recognised blood test to assess ovarian reserve and does not fluctuate based on the timing in the menstrual cycle therefore results are likely to be more reliable in comparison with other hormone levels which fluctuate depending on cyclical changes and reply on patients attending at the right time in their menstrual cycle.

High vaginal swabs are collected in line with guidelines to identify any potential infection prior to the HyCoSy procedure so any abnormal results may be treated to prevent further spread of infection.

Trans-vaginal ultrasound scanning is used to assess pelvic anatomy, looking at the size and contour of the uterus and ovaries, and noting follicular activity and endometrial thickness in reference to the timing in the cycle.

HyCoSy (Hysterosalpingo Contrast Sonography) is an investigation of the fallopian tubes to check if they are open (patent). Ultrasound scanning is used to check for spillage from the fallopian tubes.  It is done under intravenous conscious sedation to ensure it is not painful for patients. It is an alternative to the traditional HSG procedure (X-ray Hysterosalpingography) offered on the NHS and uses X-ray to check for spillage of radio-opaque media from the fallopian tubes.

Semen analysis is carried out by the Senior Clinical Embryologist in line with WHO 2010 standards. All semen parameters are tested including: volume, concentration, count, morphology, motility, pH, agglutination and leucocyte count.

some patients who had no fertility treatment after the one stop package were lost to follow.

Conclusion

The audit supports the use of the One Stop Fertility Diagnosis Package. A number of patients conceived following the package with no treatment at all, which may be partially attributed to the positive effect of the HyCoSy procedure flushing through the Fallopian tubes. Patients are also offered advice at initial consultation and at review on optimum frequency and timing of intercourse which may play a part in improving fertility outcomes for some patients.

In most cases, the tests were completed within 2months.

The package is successful in identifying the fertility status of couples considering fertility treatments and helps to determine which treatments are available to them.

HyCoSy is a safe procedure to assess tubal patency. It is performed under conscious sedation, and well tolerated. There were no complications during and after the procedure, in all cases.

The package is excellent value for money – the package cost is only half of the total cost if the tests were done individually outside the package.  

          KEY POINTS

 

·  The one stop package is successful in reaching a Fertility Diagnosis for patients, with a significant proportion of test results showing some kind of abnormal results, which may then be treated.
- 21% of AMH blood test results were defined as ‘low’
- 41% of High Vaginal Swab results were abnormal
- 15% of HyCoSy results showed problems with tubal patency
- 46% of semen analysis results showed reduced parameters
By diagnosing the problem, appropriate options for fertility treatment can be discussed to maximise your chances of conceiving.

·  34% of couples conceived after the One Stop package, the majority of whom had no treatment at all or simple ovarian induction treatment with tablets and ultrasound monitoring scans.
The One Stop package alone increases your chance of conceiving due to the positive effect of flushing the fallopian tubes through during the HyCoSy procedure, treating abnormal High Vaginal swab results, lifestyle reviews and use of supplements with abnormal Semen Analysis results, and giving advice on preconception health and optimal frequency of intercourse.

·  The package is completely safe.
No patients had any adverse reactions or complications arising from any of the investigations done as part of the One Stop Fertility Diagnosis Package. No patients required additional review appointments or readmission.



Tuesday, 9 June 2020

COVID-19 and Human Reproduction: Joint Statement released by three Fertility Medicine Societies


COVID-19 and Human Reproduction Joint Statement: ASRM/ESHRE/IFFS

  08 June 2020

Declaration of principle

Reproduction is an essential human right that exists regardless of race, gender, sexual orientation or country of origin.  Infertility is the impairment of reproductive capacity; it is a serious disease that affects 8-12% of couples of reproductive age and harms physical and mental well-being.  Infertility is time-sensitive, and prognosis worsens with age.  While there is no cure for most causes, the disease is most often treatable, and the majority of patients who seek treatment can ultimately become parents. 

Defining the problem

The COVID-19 pandemic presents a unique global challenge on a scale not previously seen. The infectivity and mortality rates are higher than previous pandemics and the disease is present in almost every country.  The propagation and containment have varied widely by location and, at present, the timeline to complete resolution is unknown. In the earliest stages of the pandemic, the American Society for Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) independently recommended discontinuation of reproductive care except for the most urgent cases.  More recently, with successful mitigation strategies in some areas and emergence of additional data, both societies have sanctioned gradual and judicious resumption of delivery of full reproductive care. In this document, ASRM, ESHRE and the International Federation for Fertility Societies (IFFS) have come together to jointly affirm the importance for continued reproductive care during the COVID-19 pandemic.

Reproductive medicine is essential

The cost of delivering all forms of medical care during the pandemic will rise due to demand for ancillary medical services and supplies including appropriate Personal Protective Equipment (PPE), additional testing, and other point of care (POC) measures. Reproductive care is essential for the well-being of society and for sustaining birth rates at a time that many nations are experiencing declines.

During the pandemic, reproductive medicine professionals should continue to:

1.     Advocate for the well-being of patients.

2.     Monitor local conditions, including prevalence of disease, status of government or state regulations, and availability of resources.

3.     Implement proactive risk assessment within their practices.

4.     Prioritize care and judiciously allocate use of limited resources using medical criteria.

5.     Counsel patients about all options, including deferring evaluation and treatment.

6.     Adhere to active risk mitigation strategies to reduce the risk of viral transmission.

7.     Develop clear and codified plans to ensure the ability to provide care while maximizing the safety of their patients and staff.

8.     Remain informed and stay current regarding new medical findings.

9.     Develop or refine robust emergency plans.

10. Be prepared to interrupt medical treatment if conditions warrant discontinuation.

Research

In addition to helping patients, reproductive medicine practices are uniquely positioned to gather data and help to further COVID-19 research.

1.     Reproductive medicine professionals and practices are essential front-line resources for screening, monitoring and assessing the prevalence and impact of the disease on patients and their progeny through POC data collection.

2.     ESHRE, ASRM and IFFS and are committed to continuous monitoring of the effect of COVID-19 on gametes and reproductive tissues, collecting data on pregnant patients infected during the pandemic, and assessing the outcomes of mothers and neonates.

3.     Examples of these research and registry efforts are:

a.     In the U.S.A., the ASPIRE (Assessing the Safety of Pregnancy In the Coronavirus Pandemic) Study is a nationwide prospective cohort study of pregnant women and their offspring during the COVID-19 pandemic. All patients under the care of a reproductive medicine specialist who conceive spontaneously or with assisted reproductive technology (ART) between March 1st and December 31st are encouraged to participate.

b.     ESHRE is gathering global case-by-case reporting on the outcome of medically assisted reproduction (MAR) conceived pregnancies in women with a confirmed infection (https://nl.surveymonkey.com/r/COVID19ART).

c.     The affiliate society of ASRM, the Society for Assisted Reproductive Technologies (SART) is including mandatory COVID-19-related questions in their Clinic Outcome Reporting System (CORS) registry of assisted reproductive technologies (ART), which accounts for over 95% of all ART cycles in the U.S.A.

d.     ESHRE is gathering data and mapping MAR/ART activity during the pandemic, country by country whether and /or when they stopped offering treatment and when they have resumed care.

e.     IFFS is conducting periodic surveys to assess global trends in access to MAR/ART services.

Final thoughts

Reproductive care is essential and reproductive medicine professionals are in a unique position to promote health and wellbeing. In addition, ASRM, ESHRE and IFFS are collaborating to advocate for patients and to gather data and resources to enhance the understanding of COVID-19 as it pertains to reproduction, pregnancy, and the impact on the fetus and neonate. The lessons learned from these will be useful as humanity deals with future pandemics.


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Vol.16, JUNE 2020, Recurrent IVF failure: What to Do

Recurrent IVF Failure - What to Do Mr J. Adeghe PhD, FRCOG.,  Consultant – Fertility & Gynaecology St Jude Hospitals & Clinics, ...