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Thin Endometrium
The definition and cut-off for thin endometrium differs between studies & clinics.
Most commonly use cut off are endometrial thickness 7 mm or 8 mm on the day of ovulation trigger.
Thin endometrium can affect fertility in following ways :
Failure of implantation
Increased risk of abortion
Following conditions can causes thin endometrium:
- Formation of scar tissue due to any surgery like DNC, fibroid surgery, polyp removal.
- For Formation of scar tissue due to infection like tuberculosis , PID & other infections.
- Intrauterine adhesion
- Asherman syndrome
- Low estrogen hormone level
- Prolonged use of oral contraceptive pills (OCP )
- Excessive use of clomiphene citrate.
These tests are done to evaluate cases with thin endometrium:
– Detailed 2D & 3d USG
– Hysteroscopy to directly inspect the lining of uterus
– Saline sonography
Treatment of thin endometrium :
- Surgical removal of adhesions if identified during hysteroscopy.
- Change in estrogen hormone protocol.
- Use of Tamoxiphene citrate.
- Use of adjuvant medications to increase blood flow in uterus.
- Intrauterine infusion of regenerative substances to promote repair & growth of uterine lining like GCSF , fibrin , PRP or stem cell.
Fibroid Uterus
Fibroids are also called Myoma or leiomyoma Fibroids occur in 50–60% of women by the age of 40yr. The chance of having fibroid increases with age.
When to suspect presence of fibroid in uterus ?
Heavy bleeding and/or pain during periods.
Pressure symptoms due to large size of myoma causing pain/difficulty in passing urine, constipation, pain during bowel motion.
Pregnancy complications like abortion, preterm labour, pain etc.
How fibroid can affect fertility ?
Presence of fibroid can reduce fertility due to following effects :
-
- Direct pressure over uterine cavity & fallopian tubes.
- Change in direction of uterine cavity & fallopian tube.
- Change in receptivity of lining of uterus.
- Change in direction of normal Junctional zone contraction waves.
- Recurrent Implantation Failure.
How fibroid can affect pregnancy ?
– Presence of fibroid can have following adverse effects on pregnancy :-
- Risk of abortion.
- Risk of preterm labour pain (delivery before 9 month)
- Intra uterine growth restriction (low birth weight baby)
- Wrong position of baby in uterus (Malpresentation)
- Rupture of water bag before delivery date (PROM)
- Separation of placenta from uterus (Abruption)
- More chances of delivery by caesarean section
How is fibroid treated ?
In women planning to conceive options are :-
- Myomectomy : Surgery to excise the fibroids
- Medical management : Drugs like GnRH agonist & SPRM( selective progesterone receptor modulator ) to shrink the fibroid away from uterine cavity
- No treatment : It is chosen if fibroid is unlikely to affect fertility & pregnancy.
Who should undergo surgery to remove fibroid (myomectomy) ?
It’s a very individualised decision as fibroids are very commonly seen in otherwise fertile women also. The decision to remove fibroid is based on detailed fibroid mapping , using 2d & 3D USG to assess the following :-
- Location of fibroid -those towards cavity should be removed
- Size of fibroid – larger than 4 cm should be removed
- Number of fibroids – 2 or more in number are better removed
- Closeness to the lining of uterus – Cavity distorting fibroid should be removed.
What to expect after fibroid removal?
- Couple can start trying for pregnancy after 2-3 month.
- After myomectomy delivery by caesarean section is recommended.
Unexplained Infertility
Unexplained infertility can affect 15-30 % of infertile couples. It is diagnosed if a couple fails to conceive after 1 year of regular sexual intercourse even though investigations for ovulation, tubal patency and semen analysis are normal. Unexplained infertility is a diagnosis of exclusion.
Unexplained infertility can happen due to 2 reasons
1) Some couples may have some subtle, undetected defect in the reproductive process which cannot be detected by routine fertility tests.
2) Pregnancy is delayed by chance alone, as the couples fecundity may be on the lower side of the normal fertility.
The possibility of pregnancy with natural methods is less if any of the following issues are there :
- Woman’s age is more than 35yrs : For each year of the female partner’s age after 30, the pregnancy rate is reduced by 9 %.
- Couple has already tried for more than 3 years : Each additional month of infertility beyond the average reduces the chance of pregnancy by 2 % ie about about 25%/year.
- There was no pregnancy earlier.
Potential contributing factors which are not detected by routine tests are:
- Effects of poor lifestyle & diet, smoking, environmental pollution , psychological stress.
- Low ovarian reserve
- Poor quality /immature oocyte
- High DNA damage in sperm
- Abnormal tubal function
- Abnormal fertilisation , embryo development
- Abnormal endometrial receptivity
- Sub clinical infections
- Immunological factors
Management options are focused on identifying the causes without adding much to the cost & pregnancy can be achieved with:
- Expectant management
- Ovulation induction & IUI
- Hystero laparoscopy
- IVF & ICSI
Polycystic Ovarian Syndrome/Disease (PCOS/PCOD)
PCOD is a condition which can causes irregular period & ovulation problems despite having more than normal number of eggs in ovaries. It is a condition which affects women from all age groups from adolescent age till old age.
Additionally PCOD can cause:
- Hirsutism – excessive facial & body hairs
- Acne
- Male pattern baldness
Women with PCOD are at increased the risk of following :
- Type 2 Diabetes
- Risk of cardiovascular diseases
- Risk of endometrial hyperplasia & endometrial cancer
- Risk of anxiety & depression
Woman with PCOD are at higher risk of pregnancy complications:
- Risk of miscarriage
- Risk of preterm labour
- Risk of diabetes during pregnancy
Routine tests & evaluation in PCOD includes:
- Pelvic ultrasound & assessment of ovaries
- Hormonal assessment : LH, testosterone , AMH, DHEAS
- BMI & waist circumference
- Glucose challenge test
- Blood pressure
- Assessment of depression or anxiety
Treatment of PCOS is aimed at correcting the present concern of the patient:
- Ovulation problems
- Correction of period irregularity
- Weight reduction
- Individualised care during pregnancy
- Lifelong follow up to monitor the risk of diabetes & cardiovascular diseases.
Options for fertility treatment for PCOS women are:
- Ovulation induction
- Intrauterine insemination (IUI) if any male factor is present
- Laparoscopy
- IVF
- Prevention of miscarriage
Some infertile women with PCOS may need laparoscopy for following indication:
- Women who fail to ovulate with oral tablets.
- High levels of LH & AMH.
- High risk for Ovarian hyperstimulation syndrome with hormones injection.
- Women who need assessment of fallopian tubes.
- Cannot come for repeated follicular monitoring.
- Normal male factor with fair chance of natural pregnancy.
There are conditions other than PCOS which can cause similar issues:
- Thyroid disorders
- Prolactin disorders
- Cushing syndrome
- Idiopathic hirsutism
Important things to consider during your PCOS treatment:
- PCOS is a very complex hormonal , metabolic , lifestyle & psychological issues.
- It is a lifelong condition.
- It is a lifelong condition.
- Before labelling a woman as having PCOS it is important to make sure that there are no other hormonal conditions which can cause similar issues.
- It requires individualised evaluation & treatment planning.
Endometriosis
- Endometriosis is the presence of endometrium -like tissue outside the uterus.
- Endometrium is natural inside lining of cavity of uterus.
- Endometriosis induces a chronic inflammatory reaction leading to scar tissue and adhesions formation.
- 25 to 50% of infertile women have endometriosis.
- 30 to 50% of women with endometriosis suffer from infertility.
- Diagnosis of endometriosis is made by physical examination, ultrasonography & /or laparoscopy.
- Women with endometriosis usually require long term follow up with doctor.
- It can be a progressive disease with no permanent cure.
Common symptoms of endometriosis are :
- Painful periods
- Pain before periods
- Pain during intercourse
- Infertility
- Pain during bowel movement or passing urine during periods
There are 3 main types of endometriosis depending upon the location
- Superficial peritoneal lesions
- Ovarian endometriomas ( penetrating inside ovarian tissue & forming cyst )
- Deep infiltrating endometriosis :Penetrating deep under pelvic organs like urinary bladder & bowel.
Fertility treatment options for women with endometriosis depend upon following factors:
- Age of woman
- Duration of infertility
- Ovarian reserve
- Stage of endometriosis
- Severity of pain symptoms due to endometriosis
- Husband’s semen quality.
Based on the above factor these are the treatment options for women with endometriosis planning to conceive:
- Expectant management – wait for a pre decided time duration for pregnancy to happen naturally
- Ovulation induction& intrauterine insemination (IUI)
- Laparoscopy to confirm the diagnosis , check condition of tubes ,remove adhesions & remove endometriotic cyst.
- Endometriotic cyst aspiration
- IVF & ICSI
Failed IVF
Repeated IVF failure is a very disappointing condition for couple as well as the fertility specialist. Repeated IVF failure is a broader term which includes Recurrent Implantation Failure ( RIF )along with other reasons of failure of IVF like cancelled treatment in cases of poor ovarian response during stimulation, advanced age, immature oocytes, no oocyte available, no sperms available, poor quality embryos etc.
Recurrent Implantation Failure (RIF) :
- Recurrent implantation failure (RIF) is failure to conceive after 2-3 embryo transfers attempts.
- RIF can happen either due to issues in embryo quality where an abnormal embryo fails to implant in receptive (ready for implantation) endometrium or due to endometrial receptivity issues where a normal embryo fails to implant due to non-receptivity of endometrium.
- The treatment of repeated IVF failure & RIF is tailored towards identifying & correcting those issues.
Embryo quality issues can be due to:
- Advanced maternal age- high risk of chromosomal abnormality in oocytes
- Poor oocyte(egg) quality
- Parental chromosomal abnormalities
- Poor quality sperm
- High sperm DFI (DNA Fragmentation Index)
- Hardeningof Zona pellucida (outer covering of the egg)
- Suboptimal embryo culture conditions
- Smoking
Endometrial receptivity issues can be due to:
- Defect in anatomy (size & shape) of uterus : Polyp , fibroid, adenomyosis, thin endometrium (lining of uterus), adhesions, septum.
- Endometritis (infection of endometrium)
- Defect in function of endometrium
- Immunological factors causing rejection of embryo
- Thrombophilia (blood clotting disorders)
- Presence of hydrosalpinx (liquid filled fallopian tubes)
Treatment is based on correction of above factors like:
- Improvement in oocyte & sperm quality with life style changes & medications.
- Optimal ovarian stimulation protocol
- Optimal embryo culture conditions
- Blastocyst culture
- Selection of normal embryo having normal chromosomes with Preimplantation genetic test for aneuploidy (PGT-A)
- Surgical correction of uterine defects
- Assessment of endometrial receptivity with Endometrial receptivity array (ERA)
- Improving endometrial receptivity with G-CSF /PRP intrauterine infusion.
- Use of Intralipid to help in implantation.
- Immunotherapy
Embryo quality issues can be due to:
- Advanced maternal age- high risk of chromosomal abnormality in oocytes
- Poor oocyte( egg) quality
- Parental chromosomal abnormalities
- Poor quality sperm
- High sperm DFI (DNA Fragmentation Index)
- Zona pellucida hardening (its covering of oocyte)
- Suboptimal embryo culture conditions
- Smoking
Endometrial receptivity issues can be due to:
- Defect in anatomy (size & shape) of uterus : Polyp , fibroid, adenomyosis, thin endometrium (lining of uterus), adhesions, septum .
- Endometritis (infection of endometrium)
- Defect in function of endometrium
- Immunological factors causing rejection of embryo
- Thrombophilia (blood clotting disorders)
- Presence of hydrosalpinx (liquid filled fallopian tubes)
Treatment is based on correction of above factors like:
- Improvement in oocyte & sperm quality with life style changes & mediation
- Optimal stimulation protocol
- Optimal embryo culture conditions
- Blastocyst culture
- Selection of normal embryo having normal chromosomes with PGT-A
- Surgical correction of uterine defects
- Assessment of endometrial receptivity with ERA
- Improving endometrial receptivity with G-CSF /PRP intrauterine infusion .
- Use of Intralipid .
Failed IUI
Intrauterine insemination is one of the commonly performed fertility procedures.
It is relatively simple , less costly & easily acceptable to many infertile couples.
It is relatively simple , less costly & easily acceptable to many infertile couples.
With more number of ovulating eggs the success rate can rise up to 20-22 % , but at significant risk of multiple pregnancy.
Causes of Failed IUI are following :
- Advanced age of woman
- Poor ovarian reserve
- Long duration of infertility
- Wrong timing of IUI
- Blocked fallopian tube
- Open but functionally damaged fallopian tubes
- Failed fertilisation
- Poor quality oocytes
- Poor quality embryos
- Poor sperm quality
- Thin endometrial lining
- Luteal phase progesterone deficiency
- Poor endometrial receptivity
Treatment after failed IUI depends upon identifying & correcting above factors.
The options after failed IUI are :
- Tubal patency test
- Check timing & technique of IUI
- Check method of semen preparation for IUI & quality of inseminated sperms.
- Correction of thin endometrium lining
- Assessment of DFI
- Ovarian reserve test
- Hyster laparoscopy to correct & treat any defect
- Medications to improve sperm & oocyte quality
- After assessment & correction of above factors couple can be advised to go for few more cycles of IUI or IVF.
Repeated Abortion
- Recurrent pregnancy loss is 2 or more abortions before 20 weeks of pregnancy.
- Approximately 15 % women may experience 1 abortion during their reproductive years.
- Recurrent pregnancy loss can affect 1 % of pregnant women.
Causes of Recurrent pregnancy loss are following :
- Genetic abnormalities of the embryo: Aneuploidy & translocations
- Abnormalities in uterus : congenital abnormalities , adhesions inside cavity, fibroid, adenomyosis.
- Medical conditions : diabetes, thyroid disorders etc.
- Autoimmune disorders : like SLE etc.
- Blood clotting disorders : antiphospholipid antibody syndrome etc.
- PCOD
- Cervical Incompetence
- Idiopathic : Nearly 50-70 % of cases no cause for pregnancy loss is identified.
Treatment of repeated pregnancy loss is focused around identifying &correcting the problems.
- Genetic problems
–Chromosome analysis of the couple is done. When no chromosomal abnormality is found then couple can try for natural conception or opt for PGT
-A (earlier called PGS). When a chromosomal translocation is detected then couple can opt for IVF &PGT-SR procedure to select unaffected embryos. - Abnormalities in uterus can be detected by 2D or 3D USG & Hystero laparoscopy. Any identified abnormality is then corrected before planning for next pregnancy.
- Women with Antiphospholipid antibody syndrome are treated with medicines which prevent blood clotting like aspirin & heparin.
- In cases with cervical incompetence USG is done to monitor cervical length & any early opening ( dilatation ) of cervical canal. In selected cases stich around cervical canal ( Cervical Cerclage ) can be placed at end of 3rd month of pregnancy.
- PCOD Women with recurrent miscarriage are treated with supportive hormone medication.
- Cases with unidentified causes treatment is focused on giving supportive medications.
- Counselling & correction of life style factors.
- Immunotherapy to correct immunological embryo rejections.
Decreased Ovarian Reserve
Ovarian reserve is the number as well as quality of the remaining eggs in both ovaries at a given age.
Egg quality directly affects embryo development & the ‘take home baby ‘rate.
Ovarian Reserve Test ( ORT ) helps to determine the chances of natural conception as well as with treatment.
It is very important to identify women with low ovarian reserve so that they can take important decisions regarding their own fertility in a timely manner.
Following are the risk factors for Decreased ovarian reserve :
- Family history of early menopause
- Ovarian surgery especially for endometrioma
- Surgical removal of part of ovary ( for cystectomy) or removal of one whole ovary ( Oophorectomy )
- Cancer survivors after pelvic surgery , chemotherapy or radiotherapy.
- Smoking
- Unexplained infertility
- Poor response in previous IVF cycle
- Known case of certain genetic conditions like Turner syndrome &mutation carriers like Fragile X /FMR1 /BRCA -1
Ovarian reserve should be tested in following conditions also :
- Planning fertility preservation
- Candidate for IVF
- Planning to delay pregnancy for personal reasons
Ovarian reserve can be determined with Ovarian Reserve Test ( ORT ):
- USG for Antral Follicle Count (AFC scan) Good for number of eggs.
- Blood test for determination of Anti Mullerian Hormone (AMH ) Good for number of eggs & quality to some extent.
- Blood test to assess function of ‘Hypothalamic -Pituitary -Ovarian axis’ Follicle Stimulating Hormone (FSH,) Luteinising Hormone (LH) &Estradiol.
Caution while interpreting result of ORT :
- None of above test can predict the chance of pregnancy with 100 % accuracy.
- Most important factor determining chance of conception is quality of oocyte which cannot be assessed precisely with any available test.
- A woman with good ovarian reserve may face difficulty in having a healthy baby due to issues in sperm quality or implantation issues.
- Woman with low AMH & AFC also can conceive with individualised treatment protocol.
- Women with low ovarian reserve should consult a fertility specialist to discuss their treatment choices.
Fertility Preservation
Fertility preservation means preserving the ability of an individual or couple to start a family at a time feasible for them. The indications of fertility preservation can be following :
- Personal non-medical issues
- Certain health condition
- Cancer treatment
Effect of cancer on future fertility
The effect of cancer on future fertility depends upon following :
- Type of cancer
- Stage of cancer
- Type of surgery – aim is to minimise tissue damage (Fertility sparing surgery)
- Type of chemotherapy
- Dose & area of radiotherapy
- Condition of eggs & sperm before start of cancer treatment
- Age at the time of cancer diagnosis.
Fertility preservation options for women :
- Embryo cryopreservation (freezing)
- Egg cryopreservation
- Fertility sparing surgery
- Shielding of ovaries /testes with lead during radiotherapy
- Ovarian transposition to a different location.
Fertility preservation options for men
- Sperm cryopreservation
- Lead shielding of testis during radiation treatment
Fertility preservation options for children:
- It requires counselling of parents & maximum possible explanation of the process to the kid depending upon their age.
- Treatment options largely depends upon if the child has attained puberty.
Fertility preservation after puberty :
- Oocyte preservation for girls (in process similar to ovarian stimulation in IVF)
- Sperm cryopreservation for boys.
- It’s very challenging condition for fertility preservation as the child’s reproductive system is lacks mature eggs & sperms.
- Ovarian tissue & testicular tissue can be cryopreserved , but with limited success.
Other things to consider before fertility preservation:
- Early consultation with fertility specialist if you need to delay child bearing.
- Discussion with cancer specialist & fertility specialist to understand the time line & course of cancer treatment.
- Fertility preservation should not affect success of the cancer treatment when done in timely manner without delaying cancer treatment & appropriate ovarian stimulation protocol.
- Pregnancy outcome will depend on your general health condition after cancer treatment.
- Babies born after cancer treatment are generally healthy like other babies except when exposed to cancer treatment during pregnancy.
Low Or Nil Sperm Count
Issues pertaining to sperm quality can be sole cause of infertility in 20-30% of infertility cases and contribute to 40- 50% of cases of infertility overall.
Further evaluation when sperm count is low :
- 1 more repeat semen analysis as per WHO 2010 guidelines
- Post-ejaculation urine analysis ( in few cases )
- USG scrotal & /or rectal – to assess testis & assessor male glands
- Male hormones evaluation : Testosterone, FSH,LH, TSH, Prolactin
- Specialized test -Sperm vitality ( to check is sperms are alive )
- Genetic test- karyotype , Y chromosome microdeletion
- Parallel evaluation of wife for fertility status
Risk factors for low or nil sperm count include following:
- Cryptorchidism : testes not located in scrotal sac
- Testicular torsion
- Testicular trauma
- Genitourinary infections
- Exposure to environmental toxins.
- Cancer survivors – h/o chemo or radiotherapy
- Use of anabolic steroids
- Varicocele
- Smoking
- Obesity ,life style & environmental factors
- Many time no risk factor is found
Treatment options for men with very low sperm count or nil sperm:
- Men with hypo gonadotrophic hypogonadism can be treated with combined hormone therapy with HCG & FSH.
- Oral antioxidant therapy can be used
- Varicocele correction
- Treatment of MAGI – Male Accessory Gland Infectio
- Correction of life style factors , smoking cessation , weight reduction if obese.
- IUI can be done if sperm count increases above 5 M/ml
- ICSI with sperms in semen ejaculate if count does not improve above 5 M/ml
- ICSI with surgically retrieved sperms if azoospermia persists
Assisted hatching
Human embryo implants at the blastocyst stage.
At blastocyst stage, embryo starts expanding & tiny cracks are created in its shell ( Zona Pellucida ) and then embryo comes out for implantation.
Nearly 20% of human blastocysts can have hatching problems due to thick or hard zona pellucida.
Embryo hatching issues can be due to following factors :
- Cryopreservation
- Hard zona
- Extended culture
- Spontaneous
- Advanced age
- Reduction in zona lysin enzyme
- Increased zona thickness
The procedure of Assisted Hatching :
- Embryologist can create very tiny hole in zona pellucida with help of Laser shots.
- Assisted hatching can help the embryo to hatch out completely & implant in the uterus.
Assisted hatching can be suggested in following conditions :
- Woman older than 37years
- Previously failed IVF
- It is also done when embryo biopsy for genetic test is planned.
Pitfalls of assisted hatching :
- Natural expansion of blastocyst with breached ZP may be compromised & embryo may hatch out early.
- Loss of cells of embryo (blastomeres) – very rare
- Embryo may become more exposed to immunological reactions & other harmful agents.
- Monozygotic (identical) twinning of the embryo.
Blastocyst Culture
A blastocyst is 5-7 days old embryo after fertilisation.
By this time, the embryo develops an outer cell layer called Trophectoderm & cluster of cells inside it called Inner Cell Mass in fluid filled cavity called blastocele.
These are terms commonly used when we discuss about implantation of blastocyst embryo :
- Trophectoderm : It forms future placenta.
- Inner Cell Mass: It develops into baby
- Hatching of blastocyst: Before implantation, a healthy blastocyst comes out from zona pellucida in a process called hatching.
- Zona pellucida : It is the outermost hard shell of oocyte.
- It remains as protective layer around developing embryo till it hatches out at blastocyst stage.
Implantation :
- Expanded blastocyst invades inside of lining of uterus ( endometrium) within 24 hours of hatching out.
- Blastocyst embryo starts production of HCG hormone ( Human Chorionic Gonadotrophin ) which gets absorbed in the mother’s blood.
- In a healthy developing embryo, this HCG hormones keeps on increasing & can be detected by blood test of mother.
Blastocyst culture :
- Normally only 30-60 % of day 2-3 human embryo develop till blastocyst stage due to :
1. Internal factors of oocyte , sperm or embryo.
2. Sub optimal embryo culture conditions. - Earlier usual practice was to transfer 2-4 embryos at cell or cleavage stage (day 2 or 3 after IVF-ICSI) to compensate for less implantation potential of these embryos.
- Blastocyst culture helps to select embryo with higher implantation potential.
- After blastocyst culture, 1-2 embryo of can be transferred based on patient factor and higher success rate can be achieved.
- It reduces risk of triplets & high order multiple pregnancy.
- It is also recommended in cases who need embryo biopsy for genetic tests as blastocyst embryos tolerates embryo biopsy procedure better & have better implantation chance. Also, the biopsy results of a blastocyst are more reliable.
Important considerations before planning blastocyst stage embryo culture :
- Blastocyst culture requires excellent quality embryo culture condition in embryology lab.
- In suboptimal embryo culture condition embryo may show slowing or even arrest of growth , thus may fail to become blastocyst.
- Couple with less number of embryo may not have sufficient number of embryo for transfer after blastocyst culture . In such couple ‘take home baby rate ‘ per started IVF cycle is more when day 2-3 embryo transfer is done.
- Similarly embryo with lesser quality on day 2-3 of growth may become more stressed out during blastocyst culture , resulting in lower pregnancy rate per started IVF cycle when compared to day 2-3 embryo transfer.
High Sperm DFI
Sperm DNA Fragmentation Index ( DFI) is measure of damage in sperm DNA.
Sperm DNA fragmentation can affect fertilisation , embryo development & quality and hence the chances of becoming pregnant.
Sperm DNA fragmentation should be checked in couple with following conditions:
- Recurrent pregnancy loss
- Recurrent Implantation failure
- Unexplained infertility
- Exposure to environmental factors
- Low fertilisation or poor quality embryo during previous IVF
- Varicocele
- Male Accessory Gland Infection (MAGI)
- Exposure to chemotherapy or radiotherapy
- Exposure to environmental toxins such as lead
- Exposure to heat
- Steam bath or working in hot environment
- Advanced age with infertility issues
Treatment of high sperm DFI is based on correcting identified risk factor :
- Lifestyle modification
- Varicocele surgery
- Treatment of MAGI
- Antioxidant treatment
- Maintain short ejaculatory abstinence
- Sperm selection if couple is going for IVF/ICSI.
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