How to make IUI cost effective

Dr. Sharda Jain Dr. Jyoti Agarwal Dr. Jyoti Bhaskar

Dr. Abhishek Singh Parihar

How to make IUI cost effective

• Proper patient selection • Necessary investigations and optimum monitoring.

• Choosing proper drugs for controlled ovarian stimulation and IUI (COH/IUI).

• Proper sperm washing methods.

• One insemination per cycle.

• The optimum number of cycle of COH/IUI to be decided and referral for advanced procedure like IVF at the correct time.

INVESTIGATIONSIndividualize

Essential Three PRE REQUISITES

• Tubal Patency

• Male factor assessment

• Ovulation evaluation

Tubal Patency

1. Screening for tubal occlusion : Before starting IUI, screening for tubal occlusion should be performed.

2. At least One tube should be patent

IUI & Male factor

• Severe male infertility < 5 million TMSC

• Moderate Male infertility <10 million TMSC

• Mild Male infertility 10 – 15 million TMSC

Review of literature of IUI

• None of the patients with triple sperm defects conceived.

• No pregnancy was observed when the sperm concentration

before swim – up < 5 million

IUI & Male Factor

• Sperm count >15 million gives good results.

• Sperm Count Less Than 10 Million : Medical therapy with antioxidant in idiopathic male infertility improves count - Repeat Semen after 2 months.

If still <10 million/cmm or if already treated

elsewhere, then go for IVF - ICSI.

• Sperm count between 10 to 15 million- Offer IUI if not done earlier

Good Result : - Unexplained I

: - Cervical Factor I

: - Anovulatory I

: - Donor IUI

Poor Results :- Severe male infertility

Tubal factor/

Pelvic adhesions Severe endometriosis

Indications for IUI

• Couple with Unexplained Fertility problems should be offered stimulated IUI.

• Couples with Male Factor sub fertility problems should be offered unstimulated IUI if women is ovulating.

• Couple with Cervical Mucus Hostility should be offered unstimulated IUI.

• Donor Insemination IUI can also can use unstimulated cycles.

Indications for Stimulated & Unstimulated IUI:

Total Number of IUI cycles

• Couple with male factor fertility problems should

be offered up to six IUI cycles.

• Couple with unexplained fertility problems should be offered minimum three & maximum up

to six IUI cycles if < than 35 yrs.

Monitoring in (Un)/Stimulated IUI:

• Patients undergoing Controlled Ovarian Stimulation plus IUI should be monitored by transvaginal Ultrasonography.

• Patients undergoing Unstimulated IUI can be monitored by LH urinary measurements (done twice a day) after 10th day of cycle.

Choosing the Right Drug for prevention of ovarian hyper stimulation & IUI

• COHS reported five – fold increase in pregnancy rate in comparison to natural cycle.

• Although less effective than gonadotriphins,CC were more cost effective in IUI therapy.

• In Anovulation, development of single follicle by

CC should increase the chance of pregnancy .• In Ovulatory women - Aim of CC is to develop multiple follicles & thus increase the chance of

pregnancy

Dose of Gonadotropins in stimulated IUI

• The dose of gonadotropins in the first cycle of stimulated IUI should be 75 IU per day.

• The dose of gonadotropins should be raised if ovarian stimulation does not result in two or three follicles larger than 16 mm.

• If the dose of gonadotropins is raised to achieve multi follicular growth, it should be done with 37.5 IU per day per cycle.

IUI should be kept a simple procedure

• No role of Down regulation with Gnrh Agonist

• There is no role of Growth Hormones

in IUI cycles

IUI & Gnrh Antagonist

In nearly 20-25% cases of Gonadotrophin cycles, there is premature LH surge

Addition of Gnrh antagonist at the follicle size of 14mm helps such patients with

pregnancy

Timing of IUI • IUI should be performed 38 to 42 hours

after administration of hCG trigger.

• IUI should be performed 20 to 30 hours after detection of spontaneous LH surge.

Timing of hCG administration in stimulated IUI

• Patients undergoing stimulated IUI with gonadotropins should be administered hCG when the dominant follicle diameter reaches 18mm.

• Patients undergoing stimulated IUI with (Clomiphene) should be administered hCG when the dominant follicular diameter reaches 20 – 24 mm

Dose of HCG in stimulated IUI should be 5000 IU

Number of Inseminations in a cycle

Single IUI insemination is less expensive & with similar pregnancy rates as two

insemination in a single cycle.

• Proper Labeling of semen specimen

• Prolong Abstinence to be avoided (<3 or > 10 days)• Viscous Semen - Collect in bottle with media • Semen preparation - swim – up , density gradient Individualize as One size does not fit all • High quality of Consumables & media

IUI Lab secretSemen Preparation in doctor’s office or very close to doctor

• Full Bladder • Cx mucus aspiration • TARGET TIME - 90 minutes from collection to

insemination • Load – when ready • No free space at catheter tip • Rest 10 mints • Emergency tray to be kept ready

Easy IUI is the Key

Details of IUI techniques

Cancellation criteria in stimulated IUI to avoid OHSS

• An IUI cycle should be canceled if ovarian ultrasound reveal five of more follicles >=12 mm or three or more follicles >= 16 mm.

• Advice to withhold from unprotected sexual intercourse should be given if ovarian ultrasound reveal five or more follicles >=12 mm or three or more follicles >=16 mm

Special Situations

•Unexplained infertility

•Mild endometriosis

•Mild male factor infertility

In patients with

X Do not offer IUI Advice them to try to conceive for a

total of 2 years before offering IVF

(NICE Gridlines 2013)

DGF Recommendations in • Unexplained infertility

• Mild endometriosis

• Mild male factor infertility

A minimum of 3 cycles and maximum of 6 IUI cycle are recommended in above conditions

IF AGE <35 YRS

• Trial of IUI - Maximum 3 cycles with COH Can be given before offering IVF

IF > 35 YRS

• Offer IVF directly

GENERAL

• Couples who are unable to or find it difficult to have normal intercourse because of physical psychosexual

problem

• eg. man is HIV positive• Same sex relationship

SPECIFIC CONDITIONS

Intrauterine inseminationUnstimulated IUI

Insemination is to be timed around

ovulation

Women who are ovulating regularly & have patent tubes should have minimum of 6 cycles of insemination without ovarian stimulation to reduce the risk of multiple pregnancies (2004,amended 2013)

Artificial insemination for Ejaculatory disturbances

Stimulated cycle

Unstimulated cycle

If the man is HIV positive ……

The risk of transmission to the female partner is negligible if

•The man is compliant with highly active antiretroviral therapy (HAART)

•Plasma viral load is less than 50 copies / ml for more than 6 months

Unprotected intercourse at the time of ovulation Sperm washing does not further reduce the risk

of infection

If the man is HIV positive…….

But not compliant

offer sperm washing

HIV & IUI

In counseling - it should be made clear that HIV transmission can not be completely

prevented.

Insufficient evidence to recommend that HIV negative women needs pre - exposure prophylaxsis …….

Hence NOT recommended

PREGNANCY RATES PER CYCLE WITH VARIOUS TREATMENT OPTIONS

In unexplained infertility Method Pregnancy Rate (%)

Intercourse (Timed) 4 (Follicle Monitoring)

IUI 6 ---do----

CC 6 ---do----

CC+IUI 8

FSH / HMG 7.7

CC / Gondotrophins /IUI 9-12

Gondotrophins /IUI 17 – 20 %

Gondotrophins +Gnrh antagonist + IUI

25%

In vitro fertilization 20 to maximum 40 (seeing the latest US data 2014)

• Over 50 % of women under 35 years will conceive within 6 cycles of IUI

• Of those who do not conceive within 6 cycles of IUI about half will do so in next 6 cycles of IUI provided the patient is young

Chances of conception in IUIin women under 40 years

Cumulative pregnancy rate is over 75 %

No Pregnancy is invariably seen after 40 years

Success with IUI in relation to sperms

• IUI using fresh sperms is associated with higher conception rates than frozen thawed sperms .

• Intrauterine insemination is associated with higher conception rates than intracervical insemination even with frozen sperms .

• Donor sperm should always be IUI as it improves the pregnancy rates

Why Intra uterine Insemination Fails

• Poor semen preparation

• Poor selection of patients

• Improper egg pick-up by fimbria due to peritubal adhesions

• Prevalence of empty follicle syndrome or poor Oocyte quality.

Other Known causes are -Cause of infertility least pregnancy rate in male

infertility & severe endometriosis- Age >35 yrs in women & > 40 yrs in men - Duration of infertility > 5 yrs -Number of IUI cycles > 3 -sperm parameters TMSC < 5 million.- Not using controlled ovarian hyperstimulations

Why Intra uterine Insemination Fails

IVF is more Cost- Effective

• Women above 35 with Unexplained infertility

• Elderly women with Mild Male Factor (cohlen et al)

• Women with Advanced Endometriosis.

When considering IVF as a treatment option…

Discuss the risks and benefits of IVFINFORM THE COUPLE …

• One full cycle of IVF consists of

↓

• 1 episode of Ovarian Stimulation

with or without ICSI

• Transfer of fresh or frozen embryo(s)(new 2013)

Women less than 40 years who have not concieved after

* 2 yrs of unprotected intercourse or* 6 cycles of stimulated IUI

Offer full 3 cycles of IVF with / without ICSI

(new 2013)

In women aged 40 – 42 years Who have not conceived after

* 2 yrs of unprotected intercourse*2 cycles of IUI

offer IVF/ ICSI with donor eggs

Refer directly to an IVF specialist

Where investigations show there is no chance of pregnancy with expectant management , irrespective of the age Eg tubal block

IVF is the only effective treatment in these patients

(new 2013)

Summary How to make IUI cost effective ??

Or DGF’s IUI Guidelines 2014

• Minimum investigations • If gonadotrophins needed - Low dose - Type of Gn, U- FSH, HMG - Clear Cancellation protocol of cycle • USG monitoring E2 rarely • HCG of ovulation trigger or Spontaneous rupture • Use of LH kit in unstimulated cycles • One insemination in the cycle • Minimum post wash semen concentration to be about 5 -10 million• Proper sperm washing method which is cheaper • Optimum number of cycle • Referral to IVF unit at proper time

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